Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study

Abstract

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure.

Methods: We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms.

Results: The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p < 0.01) and significant decrease in transepidermal water loss (p < 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group.

Conclusion: The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Keywords: Atopic dermatitis; Comparative study; Lamella; Pseudo-ceramide; Steroid.

Fig. 1

Structure of synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide)

Fig. 2

Test design. Following the 1-week washout period, test cream or control cream was applied twice per day on the arm for 2 weeks

Fig. 3

Lamellar structure of the test cream under a transmission electron microscope. The layered structure with intervals of less than 10 nm was observed

Fig. 4

Structure of the test and control cream analyzed using X-ray scattering analysis. A The test cream (red line) showed a peak at q = 0.765 nm⁻¹ and a lamellar structure with a periodicity phase of approximately 8.2 nm (a). A clear peak was also observed at q = 15.4 nm⁻¹ in the test cream (b). B The control cream (blue line) showed no clear peak within the q = 0.05–1 nm⁻¹ range. Multiple peaks from crystal structures appeared around q = 15.4 nm⁻¹ in the control cream (c)

Fig. 5

Assessment of severity at the test sites following drug application. Significant improvements were observed between weeks 0 and 2 in both groups. No significant differences were observed between the groups. *p < 0.01 (Scheffé’s multiple comparison test)

Fig. 6

Changes in skin hydration and transepidermal water loss. A No significant changes in the control group (n = 17). Significant increase in the test cream group (n = 17) (mean ± SE, **p < 0.01, Holm–Bonferroni method, versus week 0). The changes in the skin hydration value at weeks 1 and 2 in the test cream group were significantly higher than those in the control cream group (^††p < 0.01, Student’s t-test). B Transepidermal water loss significantly decreased in the test cream group following application (mean ± SE, *p < 0.05, Holm–Bonferroni method, versus week 0). The changes in transepidermal water loss in the test cream group at weeks 1 and 2 were significantly lower than those in the control cream group (^†p < 0.05, Student’s t-test)