Evaluation of the effectiveness and safety of a new formulation of Cold Cream in patients with atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder, frequently characterized by severe itching and eczematous lesions. The traditional Cold Cream, an water-in-oil cream made up by beeswax and borax, is used in the clinical practice to relieve AD symptoms, although its effectiveness has not scientifically been proved. Furthermore, the officinal formula of this cream, the Cold Cream Pharmacopoeia, presents a low physical stability. Therefore, this work aimed to prepare and characterize stable Cold Cream formulations and understand how Cold Cream can contribute with AD treatment. The influence of beeswax purity of the creams on the mechanical, texture and rheological characteristics was investigated. The components of the green propolis present in raw beeswax were identified and anti-inflammatory properties were investigated in vitro and compared to a standardized extract of green propolis. The effect of using propolis-free and propolis-added (at the same concentration as raw beeswax) Cold Cream formulations on life quality, disease severity and skin hydration of AD patients from the FMRP-USP Hospital das Clínicas (CAAE 83521418.5.0000.5403) was also assessed. Identification of the major components of the raw and purified beeswaxes was carried out using GC/MS. Artepelin C, the main marker of propolis, was quantified using HPLC after separation of the representative components of green propolis from the raw beeswax. Methanolic extract of raw beeswax ranging from 6.25 to 25 µg/mL, which respectively corresponds to artepelin C concentrations from 3.5 to 14 ng/mL, was used to treat AMJ-2 macrophage culture previously stimulated with LPS. The results showed a significant reduction in IL-6 and TNF-α levels, suggesting an anti-inflammatory effect of the beeswax extract. The raw beeswax cream (Cold Cream B.), the propolis-free purified-beeswax cream (Cold Cream P.) and the propolis-added purified-beeswax cream (Cold Cream P. + Propolis) were stable in terms of rheology and sensorial characteristics over a 60-day storage period. Conversely, Cold Cream Pharmacopoeia showed changes in rheological characteristics along with oil phase separation after 30 days. The Cold Cream Pharmacopoeia prepared with purified beeswax presented mechanical and bioadhesion properties similar to those of the Cold Cream P. and Cold Cream P. + Propolis. On the other hand, Cold Cream B. showed hardness and compressibility properties decreased by 3 times and cohesiveness and bioadhesion strength properties increased when compared to the purified-beeswax prepared creams. Human clinical study showed that Cold Cream prevented worsening of AD. In addition, the analysis of the evaluative instruments used in clinical study suggested that the addition of small concentration of propolis to the Cold Cream improved the life quality of patients, skin hydration and disease severity. (AU)