Effective treatment for sensitive skin: 4-t-butylcyclohexanol and licochalcone A.

BACKGROUND: More than 50% of adults report to suffer from sensitive skin. This common condition is characterized by subjective sensations such as prickling, burning, skin tightness or pruritus, and is often accompanied by objective symptoms like inflammation and erythema. OBJECTIVE: The objective of this study was to develop an active ingredient concept for the treatment of sensitive skin. We tested compounds regarding their potential to (i) decrease the release of proinflammatory mediators, which among others induce erythema and (ii) counteract the hyperresponsiveness of nerve fibres and, thus, exert effects on cutaneous neurosensory dysfunction. METHODS: 4-t-butylcyclohexanol, licochalcone A and acetyl dipeptide-1 cetyl ester were analysed in vitro regarding their potential to (i) decrease the release of PGE2 and activation of NFκB and to (ii) inhibit TRPV1 activation or the release of neuronal CGRP. To assess subjective and objective symptoms of skin sensitivity in vivo, two controlled, single-blind, randomized studies were conducted with 4-t-butylcyclohexanol and the combination with licochalcone A. RESULTS: In vitro, 4-t-butylcyclohexanol significantly reduced TRPV1 activation, while acetyl dipeptide-1 cetyl ester had no effect on receptor activation. Licochalcone A significantly decreased NFκB signalling and PGE2 secretion, at lower concentrations than acetyl dipeptide-1 cetyl ester. A formulation containing 4-t-butylcyclohexanol showed a significant immediate anti-stinging/anti-burning effect in vivo, and a cream base containing a combination of 4-t-butylcyclohexanol and a licochalcone A-rich licorice extract reduced shaving-induced erythema. CONCLUSION: In vitro and in vivo data indicate that the combination of the TRPV1 antagonist 4-t-butylcyclohexanol and the potent anti-inflammatory licochalcone A provide an effective active ingredient concept for the treatment of sensitive skin, as the topical application resulted in an immediate relief from symptoms such as erythema and stinging.

A double-blind, randomized, vehicle-controlled efficacy assessment study of a skin care formulation for improvement of mild to moderately severe acne.

BACKGROUND: Inflammation, increased sebum production and P. acnes colonization are key factors in acne pathogenesis. Cosmetic formulations based on a combination of active compounds with in vitro proven anti-inflammatory, sebum regulating and P. acnes reducing properties may therefore contribute to improve the clinical signs and associated burden of disease. OBJECTIVE: To provide in vivo proof-of-concept, we performed a 9-week, double-blind, randomized, vehicle-controlled study to assess the stand-alone efficacy of a skin care formulation containing licochalcone A, l-carnitine and 1,2-decanediol in volunteers with mild to moderately severe acne (10-25 inflammatory lesions) involving the face. MATERIALS AND METHODS: After enrolment followed by a 1-week standardization of the cleansing procedure, 60 volunteers aged 14-40 years (40 women and 20 men, mean age 22.4 years) were randomized into two groups of 30 volunteers each, to apply either the active formulation or the vehicle twice daily on the face for 8 weeks. Reduction in the lesion count, P. acnes and sebum levels, stratum corneum hydration, Dermatology Life Quality Index (DLQI) and skin tolerability, assessed after 4 and 8 weeks were defined as outcomes. RESULTS: Compared to baseline, the active formulation group showed at the end of the study a reduction in the mean total lesions count and papular lesions, significant reduction in the pustules (P < 0.05) and sebum levels (P < 0.01), marked reduction in P. acnes and improvement of DLQI. No significant changes in the respective parameters were found in the vehicle group. At the end of the study, greater reduction in the total lesion count, papules and pustules, P. acnes colonization, sebum production and more pronounced improvement of life quality in the active formulation group compared to the vehicle were found. CONCLUSIONS: Our results provide evidence for improved outcomes in result of the application of the active formulation compared to the vehicle from both physician's and patient's perspective.

Prevention of follicular penetration: barrier-enhancing formulations against the penetration of pollen allergens into hair follicles.

The hair follicles could be a reservoir for topically applied substances. They are not only surrounded by a close network of blood capillaries, which makes them interesting for drug delivery, but they are also the host of dendritic cells, which are important for immunomodulation. Previously, pollen allergens were shown to penetrate into the hair follicles. The application of barrier-enhancing formulations might represent an effective strategy to prevent pollen protein penetration into the hair follicle. In the present study, porcine skin areas were pretreated with 4 barrier-enhancing emulsions. One skin area served as control and remained without pretreatment. Afterwards, fluorescein-isothiocyanate-labeled grass pollen proteins were applied to the porcine skin samples, and their penetration was investigated via fluorescent laser scanning microscopy. It was shown that the barrier-enhancing formulations were able to significantly reduce the penetration of exogenous proteins into the hair follicles, the extent of such reduction depending on the formulation.

Polymorphous light eruption (PLE) and a new potent antioxidant and UVA-protective formulation as prophylaxis.

BACKGROUND: Polymorphous light eruption (PLE) is the most common photodermatosis. While its etiology still remains elusive, pathogenesis seems to involve UVA-induced oxidative stress and subsequent deregulation of antioxidative immune responses. Only few and often ineffective prophylactic and therapeutic measures exist to date. METHODS: In our randomized, double-blind, placebo-controlled clinical study, we compared the efficacy of a new topical formulation, consisting of 0.25%alpha-glucosylrutin (AGR) (a natural, modified flavonoid), 1% tocopheryl acetate (vitamin E) and a broad-spectrum, highly UVA-protective sunscreen (SPF 15) in a hydrodispersion gel vehicle, to a sunscreen-only gel and vehicle. Thirty patients with a history of PLE were pretreated with either the above formulation, a similar preparation (with the same concentration for vitamin E and AGR, but a different UV filter system), placebo or a SPF 15 sunscreen-only gel, 30 min prior to daily photoprovocation with UVA irradiations of 60-100 J/cm(2) to 5 x 5 cm(2) areas on the upper arms. RESULTS: After 4 days, results revealed a statistically highly significant difference (P<0.001) between the antioxidant containing formulations and placebo, and sunscreen-only formulation, respectively, in experimentally eliciting PLE. While only one patient developed clinical signs of PLE with accompanying itch in the area treated with the new antioxidant UV-protective gel formulation, 62.1% of the placebo-treated areas and 41.3% of the sunscreen-only treated areas showed mild to moderate signs of PLE. CONCLUSION: Combining a potent antioxidant with a broad-spectrum, highly UVA-protective sunscreen is far more effective in preventing PLE than sunscreen alone or placebo and should thus be employed as the prophylaxis of choice for PLE.

In vivo assessment of the efficacy of an innovative face care system in subjects with mild acne vulgaris.

The purpose of our studies was to verify efficacy and skin compatibility of a medical face care system containing 2% lactic acid (LA) as active ingredient in a specially designed vehicle (Follicle Targeting System) in adult subjects with mild acne vulgaris. The first study (46 patients) demonstrated superiority of 2% LA in comparison to 2% salicylic acid with respect to number of comedones and inflammatory lesions. The second study evaluated 90 patients receiving distinct combinations of face care products (Eucerin) Impure Skin, Hamburg, Germany), i.e. cleansing gel, facial tonic (2% LA) and cream gel (2% LA). All treatments were performed twice daily over a 12 weeks period. Lesion counts, cyanoacrylate biopsies and determination of quality of life by questionnaires were performed at different timepoints. A reduction of comedones by 56% corresponding to an 46% increase of quality of life index was demonstrated in patients applying cleansing gel, facial tonic and cream gel. For the first time we were able to show a significant improvement concerning the quality of life after using a new face care line. Especially adults with mild forms of acne may benefit from this effective skin care regimen.

Modulation of atopy patch test reactions by topical treatment of human skin with a fatty acid-rich emollient.

Measures directed at improving the skin barrier function are thought to be effective in preventing reexacerbation of atopic dermatitis, but direct proof of a prophylactic effect of emollients has been elusive. In the present study, the atopy patch test has been employed as a model for the initiation phase of atopic dermatitis in order to assess whether pretreatment of non-lesional skin with a fatty acid-rich emollient (Eucerin Omega Creme) has a prophylactic effect in patients with atopic dermatitis. Pretreatment of test sites with Eucerin Omega Creme either prevented or diminished the development of eczema, as compared with untreated control test sites in the same patients (n = 38). These studies indicate that the use of fatty acid-rich emollients prevents the development of atopic eczema. They also demonstrate that the atopy patch test can be used to assess the capacity of a given regimen to exert prophylactic effects in this disease.

Anti-inflammatory efficacy of topical preparations with 10% hamamelis distillate in a UV erythema test.

In 40 volunteers the efficacy of three lotions with 10% hamamelis distillates from different suppliers, two vehicles, dimethindene maleate 0.1% gel, hydrocortisone 1% cream and hydrocortisone 0.25% lotion were investigated in a modified UV erythema test with three UV dosages (1.2, 1.4 and 1.7 MED). The test preparations were applied occlusively over a 48-hour period following irradiation. Chromametric measurement of redness and visual assessment were performed 24, 48 and 72 h after induction of erythema. The hydrocortisone formulations were most effective in erythema suppression. An anti- inflammatory effect was noted for all three hamamelis lotions as well as for the vehicles. A significantly greater suppression of erythema than seen with the vehicles was noted for one of the hamamelis lotions at 1.4 MED. The efficacy of the antihistamine dimethindene maleate did not surpass the hamamelis lotions or the vehicles. Even though the differences between the hamamelis lotions were slight, it was possible to make an objective selection of the best hamamelis distillate for aftersun purposes.

Results of photoprovocation and field studies on the efficacy of a novel topically applied antioxidant in polymorphous light eruption.

BACKGROUND: UVA-induced photooxidation is considered to play an essential role in the pathogenesis of polymorphous light eruption (PLE), and topical pretreatment of skin with alpha-glucosylrutin (AGR), a potent plant-derived antioxidant, has been shown to significantly suppress photoprovoked PLE eruption. AIM: In order to further elucidate the optimum pretreatment regimen and to investigate the efficacy and skin compatibility of topical preparations containing AGR under field conditions, two controlled clinical studies were conducted in PLE patients. METHODS: In the first study, photoprovocation of PLE was performed in 20 patients, using UVA irradiation (4 x 60-100 J/cm(2)), applied to four test sites at the individual areas of predilection. One site served as an untreated control. The remaining three sites received treatment with a SPF 15 sunscreen containing 0.25% AGR (Eucerin Gel Cream Phase 2) 30 minutes before irradiation. Two of these sites were additionally pretreated with the corresponding AGR-containing vehicle (Eucerin Gel Cream Phase 1) twice daily for 3 and 7 days, respectively. The second study was conducted as a controlled in-use-test in patients with PLE (n = 27) or acne aestivalis (n = 3), who had suffered from the disease during their last year's vacation. They were educated to apply the pre-sun preparation to the formerly affected skin areas twice daily for 1 week before their planned vacation and to use the SPF 15 sunscreen 30 minutes before each vacation sun exposure. Symptoms were recorded in patients' diaries throughout the vacation and documented by a physician after their return. RESULTS: In the first study, protection of skin with the SPF 15 sunscreen alone led to a significant prevention of PLE symptoms, especially itch, compared with the control area. Pretreatment further reduced the severity of PLE significantly and led to total prevention in 19 patients. In the second study, whereas 92.6% had reported severe and 7.4% mild PLE in the last year, there were currently only 7.4% severe cases, with 25.9% mild and 29.6% questionable cases; 37% had no symptoms at all. Also, two out of three acne aestivalis patients had diminished symptoms after treatment. CONCLUSION: The results confirm the prophylactic efficacy of the antioxidant AGR in PLE, applied as SPF 15 sunscreen alone or additionally to pretreatment with a corresponding pre-sun preparation, and also show an effect in acne aestivalis patients.

Axillary pH and influence of deodorants.

BACKGROUND/AIMS: In moist intertriginous regions, such as the armpit, the pH value is physiologically higher than in other skin regions. The regulation of the axillary pH-value was examined in an open study with 48 subjects in three groups with n=16 each. METHODS: In the first 10 days (run-in) the subjects received a standard treatment in the axilla with shaving, cleansing and application of a pH-neutral deodorant. This was followed by a 5 day treatment period with the three test products (pH5 Eucerin(R) Deodorant Roll-on, Deodorant Balsam Spray, Deodorant Cream). The study was concluded by a wash-out period with procedures identical to the run-in phase. The pH was measured with a calibrated pH-meter. RESULTS: A significant pH reduction was shown during the treatment period when compared to the run-in phase. The Deodorant Roll-on induced a reduction of the mean pH values from 6.1 to 5.3, the Deodorant Balsam Spray from 6.5 to 5.7 and the Deodorant Cream from 6.2 to 5.3. During the wash-out period all pH values returned to baseline. CONCLUSION: All of the deodorants tested demonstrated a significant reduction in axillary pH. There is evidence that a high skin pH promotes the growth of several microorganisms that produce malodor. Therefore, the regulation of pH may contribute to the deodorant efficacy of the test products.

Effect of topically applied evening primrose oil on epidermal barrier function in atopic dermatitis as a function of vehicle.

The aim of this study was to establish the effect on barrier function in atopic dermatitis of topical evening primrose oil in an amphiphilic and a stable water-in-oil emulsion. The studies were vehicle-controlled in two populations of 20 atopic subjects. Barrier function was assessed in terms of transepidermal water loss and stratum corneum hydration after a 4-week treatment period and a 1-week treatment-free period. A barrier function test with sodium lauryl sulphate (SLS) and nicotinic acid ester was also carried out. Evening primrose oil proved to have a stabilising effect on the stratum corneum barrier, but this was apparent only with the water-in-oil emulsion, not the amphiphilic emulsion. The choice of vehicle is therefore an extremely important factor in the efficacy of topically applied evening primrose oil.

Fatty acid uptake by cultured human keratinocytes grown in medium deficient in or supplemented with essential fatty acids.

Epidermal linoleic acid, i.e. essential fatty acid (EFA), is essential for cutaneous barrier function. Cultured human keratinocytes, routinely used for studies of lipid metabolism, are grown in a keratinocyte serum-free medium (KSFM), under conditions that reveal EFA-deficient cells. Here, fatty acid (FA) uptake was analysed in human adult keratinocytes grown either under EFA-deficient conditions [KSFM supplemented with 10% FCS (A) or 1% UltroserG (B)] or EFA-supplemented conditions [KSFM supplemented with a devised FA cocktail (C) or evening primrose oil (D)]. The FA composition of the total cellular lipid and major lipid fractions was analysed by gas chromatography. Cells grown with supplements A or B balanced their EFA-deficient state primarily with oleic acid. Cells grown with supplements C or D normalized to the epidermal FA composition in vivo with raised linoleic and lower oleic acid contents. When cells were grown longer than 48 h with supplements C or D decreased cell growth was observed. FA uptake was curvilinear with preference for linoleic over oleic acid under all culture conditions. The uptake of linoleic acid by cells cultured with supplement B was twice the uptake of those cultured with supplement A, while the uptake of oleic acid was similar under both culture conditions. Oleic acid uptake of cells cultured with supplement C or D was lower. These results show that the uptake of linoleic, but not that of oleic acid, is influenced by the extracellular FA composition, and that EFA-supplemented keratinocytes compared to EFA-deficient cells might serve as an in vitro model for the study of EFA metabolism.

Anti-inflammatory effect of hamamelis lotion in a UVB erythema test.

BACKGROUND: Although Hamamelis virginiana has long been used in the traditional treatment of skin diseases, there are few controlled clinical studies defining the extent of its anti-inflammatory action. OBJECTIVE: The anti-inflammatory efficacy of pH5 Eucerin aftersun lotion with 10% hamamelis distillate, the vehicle and a prior aftersun formulation were tested in 30 healthy volunteers using a modified UVB erythema test as model of inflammation. METHODS: Four UVB doses ranging from 1 to 2 MED were evaluated in each subject. Test fields on the back were treated occlusively for 48 h following irradiation. Chromametry and visual scoring were used to determine the degree of erythema in the treated fields and an untreated, irradiated control field 7, 24 and 48 h after irradiation. RESULTS: Erythema suppression ranged from approximately 20% of 7 h to 27% at 48 h in the hamamelis fields. A suppression of 11-15% was recorded in the fields treated with the other lotions. Significant differences were noted between hamamelis and these lotions. CONCLUSION: These data provide evidence for an anti-inflammatory action of the aftersun lotion with 10% hamamelis and support the usefulness of the UVB erythema test with multiple UV doses for the testing of nonsteroidal anti-inflammatory agents.

Efficacy of urea therapy in children with ichthyosis. A multicenter randomized, placebo-controlled, double-blind, semilateral study.

BACKGROUND: Ichthyoses are genetic disorders of keratinization which are uncomfortable due to their conspicuous scaling, itching and cosmetic problems. Especially in childhood, ichthyoses can lead to social discrimination and psychological problems. Efficient therapies are necessary which are safe and well tolerated. OBJECTIVE: The aim of the study was to investigate the keratolytic and moisturizing properties as well as the tolerance of a new urea lotion when applied to hyperkeratotic and ichthyotic skin in childhood. METHODS: The study was conducted as a multicenter, randomized, placebo-controlled, double-blind, semilateral investigation. Sixty children between 1 and 16 years treated one side of the most affected extremity with Laceran 10% urea lotion for 8 weeks. On the other side the urea-free Laceran lotion base was given. On each side of the body a control area was left untreated. The investigators evaluated the global severity of ichthyotic symptoms with the help of a visual analogue scale. RESULTS: The analysis of the global estimation of severity of ichthyosis showed improvements being stronger in the body areas treated with Laceran 10% urea lotion (from 4.8 to 2.0 points) than in the areas treated with the urea-free Laceran lotion base (from 4.8 to 2.5 points). The response rates were 65% after 4 weeks and 78% after 8 weeks for Laceran 10% urea lotion, 50% after 4 weeks and 72% after 8 weeks for the urea-free Laceran lotion base. CONCLUSION: It can be ascertained that Laceran 10% urea lotion has a strong positive effect on generalized ichthyotic keratinization disorders.

Effects of topically applied antioxidants in experimentally provoked polymorphous light eruption.

BACKGROUND: Polymorphous light eruption (PLE) is the most common photodermatosis, with a prevalence of 10-20% in Western European countries and in the USA. Only few preventive measures for PLE exist, while its etiology and pathogenesis are still elusive. Recent theories on pathogenesis discuss the possible influence of oxidative stress. OBJECTIVE: The presented randomized, placebo-controlled, double-blind study examines for the first time the protective effect of 3 different topically applied antioxidative preparations in experimentally photo-induced PLE. METHOD: 30 patients with a history of PLE underwent photoprovocation after having had applied 3 different formulations with antioxidants and one formulation with the vehicle only to the extensor surface of their upper arms, representing the individual site of predilection, twice daily for 1 week prior to and during the consecutive week of photoprovocation. The antioxidants used were combinations of different concentrations of alpha-glycosylrutin, ferulic acid and tocopheryl acetate. RESULTS: Evaluation after the 4th photoprovocation revealed that the development and severity of PLE and concomitant pruritus were significantly reduced by the application of distinct combinations of antioxidants. CONCLUSION: The results offer a new insight into possible pathomechanisms of PLE and suggest a new approach for preventive and therapeutic measures.