Enhanced piroctone olamine retention from shampoo for superior anti-dandruff efficacy.

BACKGROUND: Dandruff is a pervasive chronic condition which negatively impacts quality of life. Effective treatment requires efficient delivery of scalp benefit agents that control commensal scalp Malassezia levels. Delivery of benefit agents from shampoos requires balancing many technical parameters to achieve the desired outcome without sacrificing secondary parameters, such as cosmetic attributes. AIM: To develop formulation technologies that increase the shampoo delivery efficiency of the scalp benefit agent piroctone olamine (PO). Increased delivery should result in increased anti-dandruff efficacy. METHODS: Micellar Stability and Association parameters were quantified via dynamic surface tension and nuclear magnetic resonance (NMR) diffusion parameters, respectively. PO delivery has been assessed in vivo both on the scalp surface and follicular infindibula using extraction procedures and analytical analysis. Clinical anti-dandruff efficacy was assessed for an advanced delivery technology prototype in comparison to standard delivery technology. RESULTS: Shampoo prototypes have been developed that increase the delivery efficiency of PO. Both surfactant and polymer coacervate-based approaches have been developed. Decreased micellar stability results in weaker association between PO and micelles, resulting in more efficient PO retention on the scalp surface and delivery to the infundibula. Increased charge density of cationic polymers optimizes coacervation enabling improved PO delivery as well. Increased PO delivery has been shown clinically to result in higher anti-dandruff efficacy as measured by both visible flakes and underlying biomarkers. CONCLUSION: Increased efficiency PO delivery shampoos have been developed by optimization of both surfactant and coacervate parameters. The increased deposition efficiency results in significantly more products with significantly greater anti-dandruff efficacy.

CONTEXTE: Les pellicules sont une maladie chronique omniprésente qui a un impact négatif sur la qualité de vie. Un traitement efficace nécessite une administration efficace d'agents bénéfiques pour le cuir chevelu qui contrôlent les niveaux commensaux de Malassezia. L'administration d'agents bénéfiques à partir de shampooings nécessite d'équilibrer de nombreux paramètres techniques pour obtenir le résultat souhaité sans sacrifier des paramètres secondaires tels que les attributs cosmétiques. BUT: Développer des technologies de formulation qui augmentent l'efficacité d'administration du shampooing de l'agent bénéfique pour le cuir chevelu piroctone olamine (PO). Une livraison accrue devrait entraîner une efficacité antipelliculaire accrue. MÉTHODES: La stabilité micellaire et les paramètres d'association ont été quantifiés via les paramètres de tension superficielle dynamique et de diffusion RMN, respectivement. L'administration de PO a été évaluée in vivo à la fois sur la surface du cuir chevelu et sur l'indibula folliculaire à l'aide de procédures d'extraction et d'analyses analytiques. L'efficacité antipelliculaire clinique a été évaluée pour un prototype de technologie d'administration avancée par rapport à la technologie d'administration standard. RÉSULTATS: Des prototypes de shampooing ont été développés pour augmenter l'efficacité de livraison des PO. Des approches à base de tensioactifs et de coacervats polymères ont été développées. Une diminution de la stabilité micellaire entraîne une association plus faible entre le PO et les micelles, ce qui entraîne une rétention plus efficace du PO sur la surface du cuir chevelu et une livraison à l'infundibula. L'augmentation de la densité de charge des polymères cationiques optimise la coacervation, permettant également une meilleure administration de PO. Il a été démontré cliniquement que l'augmentation de l'administration de PO entraîne une efficacité antipelliculaire plus élevée, mesurée à la fois par les squames visibles et les biomarqueurs sous-jacents. CONCLUSION: Des shampooings à libération de PO à efficacité accrue ont été développés en optimisant à la fois les paramètres du tensioactif et du coacervat. L'efficacité de dépôt accrue se traduit par beaucoup plus de produits avec une efficacité antipelliculaire nettement supérieure.

Scalp application of the antioxidant piroctone olamine reduces hair shedding in an 8-week randomized, double-blind, placebo-controlled clinical study.

OBJECTIVE: Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and barrier-enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave-on product) for activity to improve hair retention. METHODS: Female subjects with self-perceived hair thinning participated in an 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment. RESULTS: Statistically significant increases in hair amount were observed by phototrichogram after use of both PO-containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values. CONCLUSION: These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.

Scalp application of antioxidants improves scalp condition and reduces hair shedding in a 24-week randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Increasing hair fullness is a global unmet need for many men and women. An approach to the problem is to decrease hair fall or shedding by reducing scalp stratum corneum oxidation and barrier damage to increase hair retention. This study evaluated a combination of functional antioxidants and barrier-enhancing cosmetic ingredients to improve scalp condition thereby enabling stronger hair anchorage and longer retention. METHODS: Male and female subjects with normal scalp condition and self-perceived hair thinning participated in a 24-week, double-blind, placebo-controlled, randomized clinical study assessing either a regimen of treatment shampoo and leave-on treatment containing functional antioxidant and barrier-enhancing agents or an identical placebo chassis shampoo control. The functional ingredients were piroctone olamine, zinc pyrithione, zinc carbonate, niacinamide, panthenol and caffeine. At baseline and after 8, 16 and 24 weeks of product use, several measurements were taken: hair shedding, total hair count (by phototrichogram), hair samples, TEWL and evaluation of biomarkers of scalp and hair conditions. Subjects also completed self-assessment questionnaires. RESULTS: Statistically significant effects for functional ingredient-containing treatment regimen versus a placebo control shampoo formulation were observed for reduced hair shedding, increased total hair count, reduced TEWL and improvement in scalp biomarker values. Subjects also noticed these improvements assessed via self-assessment questionnaires. CONCLUSIONS: These results establish that the use of functional antioxidant and barrier-enhancing agents to further improve scalp condition can enable a reduction in hair shedding and thus an increase in perceived hair fullness. The underlying improvements in scalp condition suggest the hair benefits were achieved as a result of improved scalp skin barrier and scalp condition leading to a viable preventative approach for hair thinning.

Role of scalp health in achieving optimal hair growth and retention.

We have conducted a thorough review of the literature to assess the evidence for supporting a cause-and-effect linkage between scalp condition and resultant hair condition. Over 20 epidemiological studies have been published covering a wide range of abnormal scalp conditions in which consequent impacts to the hair have been documented. A treatment study was conducted to demonstrate not only that impaired scalp condition led to impaired hair quality but that the impacts to hair are reversible upon normalization of the scalp condition. A proposed explanation involves the impact of scalp oxidative stress, which is part of the etiology of these scalp conditions as well as normal aging, in interfering with the normal keratinization of the pre-emergent hair cuticle. This perturbed cuticle impedes normal fiber anchorage and emerges more brittle and fragile than normal cuticle leading to accelerated physical degradation, mirroring the effects of chronological aging of the hair fiber. The consequences of the rapid cuticle degradation result in hair that is more vulnerable to mechanical insults and compromised overall quality.

Nous avons mené un examen approfondi de la littérature médicale pour évaluer les preuves étayant un lien de cause à effet entre l'état du cuir chevelu et celui des cheveux. Plus de 20 études épidémiologiques ont été publiées, couvrant un large éventail d'affections du cuir chevelu pour lesquelles des impacts conséquents sur les cheveux ont été documentés. Une étude de traitement a été menée pour démontrer non seulement qu'une altération du cuir chevelu entraînait une altération de la qualité des cheveux, mais aussi que les impacts sur les cheveux étaient réversibles après normalisation de l'état du cuir chevelu. Une explication proposée inclut l'impact du stress oxydatif sur le cuir chevelu, qui fait partie de l'étiologie de ces affections du cuir chevelu ainsi que du vieillissement normal, en interférant avec la kératinisation normale de la cuticule du cheveu à son point d'émergence. Cette cuticule perturbée gêne l'ancrage normal des fibres et fait émerger des cuticules plus fragiles et friables que la normale, entraînant une dégradation physique accélérée, reflet des effets du vieillissement chronologique des fibres capillaires. La dégradation rapide de la cuticule rend les cheveux plus vulnérables aux agressions mécaniques et compromet leur qualité globale.

Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity.

OBJECTIVES: To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function. METHODS: A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS: Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption). CONCLUSIONS: Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.

Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics.

Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material.

Assessing therapeutic effectiveness of scalp treatments for dandruff and seborrheic dermatitis, part 1: a reliable and relevant method based on the adherent scalp flaking score (ASFS).

BACKGROUND: Dandruff and seborrheic dermatitis (D/SD) are common and troublesome scalp conditions with the primary signs and symptoms being presence of skin flakes, pruritus, a tight feeling, and sometimes erythema. AIM: To demonstrate the reliability and relevance of a clinical model for the assessment of therapeutic efficacy of a treatment using the Adherent Scalp Flaking Score (ASFS) method to quantitate the flaking severity. METHODS: Six randomized, double-blind, parallel design studies were conducted in either North America or Asia with subjects suffering from dandruff using the ASFS grading method before and after a 3-week test product treatment period. RESULTS: Treatment with a commercial potentiated 1% zinc pyrithione (ZPT) shampoo resulted in statistically significant (p < 0.0001) improvements in total ASFS compared with the placebo cosmetic shampoo. Results were consistent across all studies, geographies, and product usage protocols (controlled on-site versus home use conditions), and were associated with statistically significant improvements in self-perception of scalp condition. CONCLUSION: The ASFS-based clinical model was demonstrated to be a reliable and proven methodology to assess the effectiveness of widely used anti-dandruff treatments. The results are consistent with patient self-assessments, establishing this methodology as relevant to patient perception of product benefits.

Assessing therapeutic effectiveness of scalp treatments for dandruff and seborrheic dermatitis, part 2: the impact of gender and ethnicity on efficacy.

BACKGROUND: Dandruff and seborrheic dermatitis (D/SD) are common and troublesome scalp conditions that affect individuals independent of gender or ethnicity. AIM: To evaluate whether population gender or ethnic origins impact the magnitude of anti-dandruff therapeutic benefit obtained from use of a potentiated zinc pyrithione shampoo treatment. METHODS: A retrospective evaluation of anti-dandruff clinical data covering a single-product technology was conducted to assess whether statistically meaningful differences were observed for gender or ethnic sub-populations. An analysis of covariance was performed on the pooled subject-level data. RESULTS: Meta-analysis of clinical data involving 1114 subjects from seven trials demonstrated the lack of statistically significant impact of gender on flaking or selected biomarker measures. Similarly, a smaller population chosen to assess ethnicity demonstrated the lack of differences between Asian and Caucasian clinical sub-population responses (flaking severity). CONCLUSION: Through the use of both expert symptom grading and objective biomarker assessments, therapeutic efficacy of a potentiated zinc pyrithione shampoo was found to be independent of gender and ethnicity, being consistent with the lack of functional differences in skin from these populations.

A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a more precise definition of scalp health.

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins.

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.

Scalp stratum corneum histamine levels: novel sampling method reveals association with itch resolution in dandruff/seborrhoeic dermatitis treatment.

Dandruff and seborrhoeic dermatitis are accompanied by bothersome itch. We have established a novel non-invasive methodology to sample histamine levels in the stratum corneum in order to facilitate an understanding of pruritogenesis in this condition. Histamine levels were assessed in two groups of subjects with dandruff before and after 3 weeks of treatment with a commercial potentiated zinc pyrithione shampoo. A comparative population without dandruff was also studied. Itch self-perception was quantified on a visual analogue scale. The histamine level in subjects with dandruff was more than twice that in those who did not have dandruff. Under conditions known to resolve flaking symptoms, the shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. This reduction in histamine was accompanied by a highly significant reduction in the perception of itch intensity. These findings suggest an association between the subjective perception of itch in the scalp and the level of histamine in the skin.

Epidermal changes associated with symptomatic resolution of dandruff: biomarkers of scalp health.

BACKGROUND: Dandruff is a common scalp condition characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect underlying histopathologic and biochemical events that must be reversed if treatment is to be effective. OBJECTIVES: This study aimed to better characterize the state of the epidermis in dandruff and to determine how a defined set of skin surface biomarkers of this state change during a successful course of treatment with a potentiated zinc pyrithione (ZPT) shampoo. METHODS: A population of dandruff sufferers was treated for 3 weeks with a commercial ZPT shampoo or a non-medicated product, and the effect of treatment on adherent scalp flake (ASF) scores was evaluated. Biopsies were taken from lesional sites at baseline and at the end of the study for histomorphometric and histopathologic analysis. Stratum corneum (SC) samples were likewise obtained for evaluation of biochemical markers of inflammation (IL-1α, IL-1RA, IL-8) and barrier integrity (keratin 1, 10, 11; involucrin; SC lipids; human serum albumin). The biomarker profile was evaluated first by comparison with that in non-dandruff subjects at baseline, and then to determine whether any treatment-induced changes were correlated with reductions in flaking in dandruff sufferers. RESULTS: Taken together, our studies showed that treatment with the ZPT shampoo led to an improvement in the overall scalp condition as assessed by the resolution of flaking, reduction in epidermal thickness and inflammatory biomarkers, and a dramatic improvement in biomarkers of epidermal barrier integrity. CONCLUSIONS: The combination of biomarkers examined appears to be a good overall descriptor of the health of the scalp in dandruff, and changes in these biomarkers track with tissue-level events that underlie clinical efficacy in the treatment of dandruff by ZPT shampoo. For the first time, we demonstrate a set of tools that extend beyond flaking scores to provide insight into specific biological changes occurring on the scalp to enable an objective assessment of scalp health.

Does tachyphylaxis occur in long-term management of scalp seborrheic dermatitis with pyrithione zinc-based treatments?

BACKGROUND: Scalp seborrheic dermatitis and dandruff (SD/D) are chronic conditions requiring long-term treatment. There is a common belief that patients frequently experience decreasing benefits over time when using a single product. This physiologic accommodation is termed tachyphylaxis. AIM: To systematically investigate the anecdotal belief that tachyphylaxis occurs in long-term treatment of SD/D using quantitative clinical assessments. METHODS: An international questionnaire completed by 722 dermatologists assessed the belief of tachyphylaxis incidence with pyrithione zinc (PTZ)-based shampoos, time course, occurrence relative to active ingredients, and effect of switching products. Two double-blind, randomized, clinical evaluations were conducted, 24- and 48-week studies, whereby a 1% PTZ shampoo, a 2% PTZ shampoo, or a matched placebo control shampoo was used by each subject for the duration of the study. Dermatologists assessed the adherent scalp flaking (scale of 0-10) at baseline and at specified intervals. RESULTS: Sixty-four per cent of responding dermatologists believed tachyphylaxis occurred with PTZ products, and most felt that tachyphylaxis occurred within 3 months of use. Evaluation of mean treatment responses vs. placebo and individual responses as a function of study duration showed a consistent benefit for all products at all time points; therefore, no evidence for tachyphylaxis was found (within 48 weeks of treatment). CONCLUSION: No evidence for tachyphylaxis in SD/D treatment by PTZ-based shampoos was found. Compliance could explain the decreasing response rate seen over time; the solution is to choose an affordable therapeutic product that is effective long term without cosmetic trade-offs.

Three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, sebaceous lipids, and individual sensitivity.

Application of new molecular and biochemical tools has greatly increased our understanding of the organisms, mechanisms, and treatments of dandruff and seborrheic dermatitis. Dandruff results from at least three etiologic factors: Malassezia fungi, sebaceous secretions, and individual sensitivity. While Malassezia (formerly P. ovale) has long been a suspected cause, implicated by its presence on skin and lipophylic nature, lack of correlation between Malassezia number and the presence and severity of dandruff has remained perplexing. We have previously identified the Malassezia species correlating to dandruff and seborrheic dermatitis. In this report, we show that dandruff is mediated by Malassezia metabolites, specifically irritating free fatty acids released from sebaceous triglycerides. Investigation of the toxic Malassezia free fatty acid metabolites (represented by oleic acid) reveals the component of individual susceptibility. Malassezia metabolism results in increased levels of scalp free fatty acids. Of the three etiologic factors implicated in dandruff, Malassezia, sebaceous triglycerides, and individual susceptibility, Malassezia are the easiest to control. Pyrithione zinc kills Malassezia and all other fungi, and is highly effective against the Malassezia species actually found on scalp. Reduction in fungi reduces free fatty acids, thereby reducing scalp flaking and itch.

Zinc and skin health: overview of physiology and pharmacology.

BACKGROUND: Zinc is known to have a critical role in overall human physiology, which likely explains many of its therapeutic uses for the last several thousand years. The specific roles zinc plays in skin health and function are less widely known yet are likely just as critical based on the manifestations of dietary zinc deprivation, which include moderate to severe dermatitis. OBJECTIVE: To provide a critical review of the scientific literature as to the physiologic importance of zinc to skin, the biochemical basis for these effects, and pharmacologic aspects of zinc therapeutics. RESULTS AND CONCLUSIONS: Skin is in a continual state of renewal, placing a high demand on zinc-based enzymes and proteins that direct this process. The importance of zinc physiologically is especially evident in studies of wound healing and inflammation reduction. During these processes, the high needs for zinc can be supplemented externally, generally increasing the rates of the natural processes. Topical zinc delivery involves the pharmacologic optimization of zinc delivery, often mediated by the solubility of the zinc material and interactions within the product matrix.

Pardon me: that's our money!

Not-for-profit healthcare providers have several options they can use to resist government attempts to apply the charitable trust doctrine to their business decisions. As a strategic defense, providers should perform internal due diligence that focuses on governing documents, financial arrangements, donations/solicitation, real estate, and charitable waste allegations.