Charakterisierung von Sonnenschutzleistung: Quo vadis?

Die Aufgabe der ersten Sonnenschutzmittel war es, die Entstehung von Sonnenbrand zu verhindern und, dem Zeitgeist der 1950/60er-Jahre folgend, die Bräunung der Haut nicht zu beeinträchtigen. Schnell entstand die Notwendigkeit, die Schutzleistung zu quantifizieren. Ursprünglich unter Zuhilfenahme des natürlichen – heute eines künstlichen – Sonnenlichts wurde eine Methode zur Bestimmung eines Sonnenschutzfaktor (SPF) entwickelt. Dieser ist heute formal als das Verhältnis zwischen minimaler erythemwirksamer UV-Dosis auf mit Sonnenschutzmittel geschützter und minimaler erythemwirksamer UV-Dosis auf ungeschützter Haut definiert (ISO 24444:2019). Drei Beobachtungen stellen die Eignung der Methode infrage: 1) Zwischen-Labor-Variabilität: Trotz strenger Normierung sind Resultate von SPF-Bestimmungen aus verschiedenen Labors und Regionen sehr großen Schwankungen unterworfen. 2) Natürliches vs. künstliches Sonnenlicht: Das Strahlungsspektrum des künstlichen Sonnenlichts unterscheidet sich von dem des natürlichen Sonnenlichts. Die mit künstlichem Sonnenlicht bestimmten SPFs (wie auf allen derzeit im Handel befindlichen Sonnenschutzmitteln abgebildet) sind im Vergleich zur SPF-Bestimmung mit natürlichem Sonnenlicht deutlich zu hoch. 3) Erythembelastung: Bei der Bestimmung des SPF werden die Probanden potenziell schädlicher Strahlung ausgesetzt. Vor diesem Hintergrund werden alternative Methoden – In-vitro-SPF, hybride diffuse Reflexionsspektroskopie (HDRS) und In-silico-Berechnungen – vorgestellt. Diese haben das Potenzial, die heutige mit erheblichen Einschränkungen verbundene Methode abzulösen. Als Sofortmaßnahme wird die Rückbesinnung auf die für alle verständliche Beschreibung niedriger, mittlerer, hoher und sehr hoher Schutz empfohlen, in Zukunft unter Berücksichtigung des Spektrums des natürlichen Sonnenlichtes

Nano ist groß! : Fakten und Mythen über nanopartikuläre UV-Filter

Zusammenfassung Seit den 1950er-Jahren sind anorganische Sonnenschutzmittel mit mikronisiertem Titandioxid (TiO2) und Zinkoxid (ZnO) erhältlich. Deren kosmetische Akzeptanz blieb beschränkt, da sie als weiße Paste auf der Haut zurückbleiben. Durch Verkleinerung der Partikel in den Nanobereich unter 100 nm wurde deren optische Eigenschaft, sichtbares Licht zu reflektieren, verringert. Nach 2000 wurden auch organische Filter in dieser Größenordnung entwickelt. Die damals herrschende Begeisterung für Nanotechnologie übertrug sich nicht auf Sonnenschutzmittel mit nanopartikulären Filtern. Verbraucher vermuten, dass die Partikel durch die Haut dringen, vom Blut aufgenommen werden, sich im Körper verteilen und Krankheiten verursachen. Nicht zuletzt aufgrund von Druck der Öffentlichkeit wurden Kosmetika – zu denen auch Sonnenschutzmittel gehören – das erste Produktsegment, in dem nanopartikuläre Stoffe strengen Regeln unterworfen wurden. Trotz fortschrittlicher Regulierung und strenger Zulassungsverfahren für nanopartikuläre Filter blieben Vorbehalte bestehen. Mögliche Gründe dafür sind mangelnde Kenntnisse über die geltenden Rechtsvorschriften oder Misstrauen gegenüber diesen, unklare Vorstellungen über das Verhalten von Nanopartikeln in Sonnenschutzmitteln und infolgedessen eine unklare Wahrnehmung von Gefahr, Risiko und Exposition. Vor diesem Hintergrund werden das Wesen und Verhalten von nanopartikulären Filtern in Sonnenschutzmitteln auf der Haut und potenziell in der Haut sowie der Regulierungsrahmen, der sicherstellt, dass nanopartikuläre Filter und die sie enthaltenden Sonnenschutzmittel sicher in der Anwendung sind, diskutiert. Abstract Sunscreen products containing inorganic micronized titanium dioxide (TiO2) and zinc oxide (ZnO) have been available since the 1950s. Their cosmetic acceptance remained limited as they persist as a white paste on the skin. By reducing the size of the particles into the nano-range below 100 nm, their optical property of reflecting visible light is reduced. After the year 2000, organic filters of this size range were developed. The enthusiasm for nanotechnology that prevailed at the time did not transfer to sunscreen products with nanoparticulate filters. Consumers suspect that the particles permeate the skin, are absorbed by the blood, and spread throughout the body causing illness. Not least due to public pressure, cosmetics—which include sunscreen products—became the first product segment in which accordingly manufactured substances were subjected to strict regulations. Despite advanced regulation and strict approval procedures for nanoparticulate filters, public reservations remained. Possible reasons for this are lack of knowledge or mistrust of the applicable legislation, unclear perception of the behavior of nanoparticles in sunscreen products and as a result unclear perceptions of hazard, risk, and exposure. Against this background, the nature and behavior of nanoparticulate filters in sunscreens on the skin and potentially in the skin, as well as the regulatory framework that ensure that nanoparticulate filters and the products containing them are safe to use are discussed

The effect of a basic skin care product on the structural strength of the dermo‐epidermal junction: An exploratory, randomised, controlled split‐body trial

Skin ageing is associated with various structural alterations including a decreased strength of the dermo-epidermal adhesion increasing the risk for shear type injuries (skin tears). Topical applications of basic skin care products seem to reduce skin tear incidence. The suction blister method leads to the artificial and controlled separation of dermis and epidermis. Therefore, time to blister formation may be used as outcome measuring the strength of dermo-epidermal adhesion. We conducted an exploratory, randomised, controlled trial with a split-body design on forearms in healthy female subjects (n = 12; mean age 70.3 [SD 2.1] years). Forearms assigned to the intervention were treated twice daily with petrolatum for 8 weeks. Suction blisters were induced on forearms after 4 and 8 weeks and time to blister formation was measured. Stratum corneum and epidermal hydration were measured and epidermal thickness was assessed via optical coherence tomography. Time to blistering was longer and stratum corneum as well as epidermal hydration was consistently higher in intervention skin areas. We conclude that topical application of basic skin care products may improve mechanical adhesion of the dermo-epidermal junction and that the parameter "time to blistering" is a suitable outcome to measure dermo-epidermal adhesion strength in clinical research

The effect of a basic skin care product on the structural strength of the dermo-epidermal junction: An exploratory, randomised, controlled split-body trial

Skin ageing is associated with various structural alterations including a decreased strength of the dermo-epidermal adhesion increasing the risk for shear type injuries (skin tears). Topical applications of basic skin care products seem to reduce skin tear incidence. The suction blister method leads to the artificial and controlled separation of dermis and epidermis. Therefore, time to blister formation may be used as outcome measuring the strength of dermo-epidermal adhesion. We conducted an exploratory, randomised, controlled trial with a split-body design on forearms in healthy female subjects (n = 12; mean age 70.3 [SD 2.1] years). Forearms assigned to the intervention were treated twice daily with petrolatum for 8 weeks. Suction blisters were induced on forearms after 4 and 8 weeks and time to blister formation was measured. Stratum corneum and epidermal hydration were measured and epidermal thickness was assessed via optical coherence tomography. Time to blistering was longer and stratum corneum as well as epidermal hydration was consistently higher in intervention skin areas. We conclude that topical application of basic skin care products may improve mechanical adhesion of the dermo-epidermal junction and that the parameter "time to blistering" is a suitable outcome to measure dermo-epidermal adhesion strength in clinical research. Keywords: prevention; skin care; skin integrity; skin tears; suction bliste

Topical bioavailability of triamcinolone acetonide: effect of dose and application frequency

The application frequency of topical corticosteroids is a recurrently debated topic. Multiple-daily applications are common, although a superior efficacy compared to once-daily application is not unequivocally proven. Only few pharmacokinetic studies investigating application frequency exist. The aim of the study was to investigate the effect of dose (Experiment 1) and application frequency (Experiment 2) on the penetration of triamcinolone acetonide (TACA) into human stratum corneum (SC) in vivo. The experiments were conducted on the forearms of 15 healthy volunteers. In Experiment 1, single TACA doses (300μg/cm2 and 100μg/cm2) dissolved in acetone were applied on three sites per arm. In experiment 2, single (1×300μg/cm2) and multiple (3×100μg/cm2) TACA doses were similarly applied. SC samples were harvested by tape stripping after 0.5, 4 and 24h (Experiment 1) and after 4, 8 and 24h (Experiment 2). Corneocytes and TACA were quantified by UV/VIS spectroscopy and HPLC, respectively. TACA amounts penetrated into SC were statistically evaluated by a paired-sample t-test. In Experiment 1, TACA amounts within SC after application of 1×300μg/cm2 compared to 1×100μg/cm2 were only significantly different directly after application and similar at 4 and 24h. In Experiment 2, multiple applications of 3×100μg/cm2 yielded higher TACA amounts compared to a single application of 1×300μg/cm2 at 4 and 8h. At 24h, no difference was observed. In conclusion, using this simple vehicle, considerable TACA amounts were retained within SC independently of dose and application frequency. A low TACA dose applied once should be preferred to a high dose, which may promote higher systemic exposur

Buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: A double-blind, randomized, placebo-controlled, crossover trial

Background: Neutralizing (buffering) lidocaine 1%/epinephrine 1:100,000 solution (Lido/Epi) with sodium hydrogen carbonate (NaHCO3) (also called sodium bicarbonate) is widely used to reduce burning sensations during infiltration of Lido/Epi. Optimal mixing ratios have not been systematically investigated. Objectives: To determine whether a Lido/Epi:NaHCO3 mixing ratio of 3:1 (investigational medicinal product 1) causes less pain during infiltration than a mixing ratio of 9:1 (IMP2) or unbuffered Lido/Epi (IMP3). Methods: Double-blind, randomized, placebo-controlled, crossover trial (n = 2 × 24) with 4 investigational medicinal products (IMP1-4). Results: The 3:1 mixing ratio was significantly less painful than the 9:1 ratio (P = .044). Unbuffered Lido/Epi was more painful than the buffered Lido/Epi (P = .001 vs IMP1; P = .033 vs IMP2). IMP4 (NaCl 0.9% [placebo]) was more painful than any of the anesthetic solutions (P = .001 vs IMP1; P = .001 vs IMP2; P = .016 vs IMP3). In all cases, the anesthesia was effective for at least 3 hours. Limitations: Results of this trial cannot be generalized to other local anesthetics such as prilocaine, bupivacaine, or ropivacaine, which precipitate with NaHCO3 admixtures. Conclusions: Lido/Epi-NaHCO3 mixtures effectively reduce burning pain during infiltration. The 3:1 mixing ratio is significantly less painful than the 9:1 ratio. Reported findings are of high practical relevance, given the extensive use of local anesthesia today

Skin care interventions in infants for preventing eczema and food allergy

BackgroundEczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy.ObjectivesPrimary objectiveTo assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infantsSecondary objectiveTo identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated withthe greatest treatment benefit or harm for both eczema and food allergy.Search methodsWe searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials.Selection criteriaRCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre‐existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow‐up was required.Data collection and analysisThis is a prospective individual participant data (IPD) meta‐analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E‐mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician‐assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen.Main resultsThis review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta‐analysis (range 2 to 9 studies per individual meta‐analysis).Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty‐five studies, including all those contributing data to meta‐analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta‐analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow‐up ranged from 24 hours to two years.We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data.Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate‐certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate‐certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE‐mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low‐certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low‐certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow’s milk, and may be unreliable due to significant over‐reporting of cow’s milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate‐certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low‐certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low‐certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk.Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy.Authors' conclusionsSkin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain.Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments