Clinical evidence on the efficacy and tolerability of a

topical medical device containing benzoyl peroxide 4%,

retinol 0.5%, mandelic acid 1% and lactobionic acid 1% in
the treatment of mild facial acne: an open label pilot
study
Components Properties Properties Properties
Benzoyl Peroxide 4% Antibacterial Keratolytic Sebum normalizing
Mandelic Acid 1% (AHA) Antibacterial Keratolytic
Lactobionic Acid 1% (AHA) Moisturizing Keratolytic

Retinol pure 0.05% Keratolytic Improvement of cellular

turnover
Retinol palmitate 0.5% Keratolytic Improvement of cellular
turnover
Zinc sulphate1% Sebum normalizing
Undecylenic acid Sebum normalizing Antimycotic activity
Glycyrrhetic acid Moisturizing Lenitive Anti-inflammatory
Phytoshingosine Moisturizing Lenitive Anti-inflammatory

Compounds of topical medical device containing benzoyl peroxide,

retinol, mandelic acid and lactobionic acid
Benzoyl peroxide
▪ Used both as a single agent and in combination with antibiotics or retinoid, based on
expected synergistic effect due to different mechanisms of action.
▪ Combined BPO and antibiotic treatment may reduce the emergence of antibiotic-
resistant Cutibacterium acnes.
▪ Directly toxic to Cutibacterium acnes.
▪ Rapid reduction of both inflammatory and non-inflammatory acne lesions within 8 – 12
weeks of treatment.
▪ Clearance of the blocked sebaceous ducts through its keratolytic effect.
Topical Mandelic Acid
▪ Large α-hydroxy acid molecule with uniform effect due to greater skin retention and
slower penetration of the strateum corneum.
▪ Viscoelastic properties.
▪ Safe superficial peeling agent.
▪ 20-50% concentrations for skin rejuvenation and lightening.
 Lactobionic acids
▪ Chelating action, antioxidant activity, and binding ability of significant amounts of water.
▪ Antioxidant activity related to the excellent properties of chelating metal ions, mainly iron
ions.
▪ Ability of scavenging the free radicals and inhibition of lipid peroxidation protecting cell
membranes and mitochondria from sun exposure damage.
▪ Inhibitor of matrix metalloproteinases mainly formed under the influence of UV radiation.
▪ Potent humectant thus softening the skin surface.
Topical Retinoids
▪ First-line treatment for non-inflammatory and inflammatory acne vulgaris.
▪ Normalize follicular keratinization.
▪ Decrease keratinocyte cohesiveness.
▪ Reduce follicular occlusion.
▪ Reduce comedone formation.
▪ Enhance penetration of other topical acne medications.
▪ Accelerate resolution of acne-induced post-inflammatory hyperpigmentation.
▪ Combination therapies of topical retinoid are superior to monotherapies, supporting
the synergistic effect of anti-inflammatory agents
Glycyrrhetic acid
▪ Anti-microbial
▪ Anti-inflammatory
▪ Anti-oxidative
▪ Attenuates inflammation and hyperpigmentation.
▪ Regulates proliferation and migration of keratinocytes and fibroblasts.
Zinc
▪ Essential micronutrient for the proper functioning of several processes.
▪ Zinc levels in acne significantly lower than controls.
▪ Regulation of protein, lipid, and nucleic acid metabolism.
▪ Regulation of gene transcription of steroid and thyroid hormone receptors.
▪ Maintenance of immunologic response
▪ Inflammatory regulation by inhibition of IL-6 and TNF-a production.
▪ Inhibition of inflammatory mediator production.
Phytosphingosine
▪ Exerts anti-inflammation and antimicrobial activities.
▪ Stimulates epidermal differentiation.
▪ Increases phytoceramide content in keratinocytes.
▪ Enhances moisture level in human skin barrier.
▪ Stimulates filaggrin biosynthesis and degradation.
▪ Restores corneocyte envelop.
▪ Induces NMF formation.
 Clinical and instrumental evaluation of
Objectives of effectiveness, safety, tolerability of a new
topical medical device in cream on patients
the study with mild facial acne.
 Mechanisms of action

phytosphingosine 0,2%

• keratolytics effect to BPO 4%

remove keratin plugs •anti-seborrheic action
•counteracts the irritative
• reach the follicle by inhibiting the 5-alpha
action of BPO and
infundibulum, release of reductase enzyme retinoids, restores the
oxygen radicals and cutaneous lipid physiology,
pure retinol 0.05% create an unfavorable exerts antibacterial
retinol palmitate 0.5% environment for C. function
mandelic acid 1% Acnes zinc sulfate 1%
lactobionic acid 1%
•anti-inflammatory activity
through the inhibition of
protein kinases
Materials and Methods
Uncontrolled pilot study, with an open-label design, conducted in the Department of
Dermatology, University of Rome Tor Vergata, Italy

➢ Twenty patients of both sexes were

➢ Inclusion criteria: age between 13-30
included in the study.
years old and clinical diagnosis of mild
acne, mainly located on the face. ➢ Each patient was instructed to apply a thin
film of the topical medical device cream
➢ Exclusion criteria: previous treatment
as a monotherapy twice a day for 12
with antibiotics, BPO or topical retinoids weeks.
(suspended at least for 4 weeks), oral
retinoids (suspended at least for 6 ➢ Clinical and instrumental evaluations were
months); endocrine disease, pregnancy performed at baseline (T0), at 4 weeks
and therapy with oral corticosteroids (T1) and after 12 weeks (T2).
 GAGS (Global Acne Grading System )
Efficacy and safety evaluations

▪ Only patients with mild facial acne (GAGS score:1-18).

▪ Results independently assessed from T0 to T2 (12 weeks):
▪ “almost clear” patients with at least 30% reduction of the initial
lesions by GAGS score.
▪ “clear” the patients with at least 60% reduction of the initial
lesions by GAGS score.
Lesion count:
the face is
▪ Lesions count: comedons, papules/pustules and nodules/cysts divided into
several regions
such as nose,
▪ Photographic assessment forehead, each
cheek, and
perioral region.
Efficacy and safety
evaluations
➢ Histopathological in vivo aspects of acne lesions and clinical
improvement were also investigated through reflectance confocal
microscopy (RCM) Vivascope 1500, evaluating keratinization,
infundibular hyperkeratinization and dermal inflammation.

➢ Moreover, a questionnaire filled by the patients to assess the

tolerability of the product (excellent, good, fair, poor) and the
presence of side effects.
Efficacy and safety
evaluations
▪ Seborrhea and hydration degree were measured
using a specific software (SoftPlus-Callegaris) at
baseline (T0) and after 12 weeks (T2).
▪ Degrees of seborrhea ranging from 30 to 60 were
defined as normal range by the software system
▪ Good level of hydration was considered for values
over 59.
Results: efficacy
▪ A total of 20 patients (9 male and 11 female) were
enrolled in the study. The mean age was 19.5 years.
▪ Comedonic acne: 8 pts
p-value < 0.05
▪ Papulo/pustular acne: 12 pts.
▪ GAGS score showed:
▪ T1: 39% reduction (almost clear)
▪ T2: 69,20% reduction (clear)
▪ mean values: 11,55 at T0; 7 at T1; 3,55 at T2
Results: efficacy –
Lesions’ count
▪ Comedonic lesions:
▪ T1: 44% reduction from T0 to T1
▪ T2: 65% reduction from T0 to T2
▪ mean values at T0 16.3; 9.1 at T1; 5.7 at T2.

▪ Papular lesions:
▪ T1: 49.4% reduction from T0 to T1
▪ T2: 62% reduction from T0 to T2
▪ mean values 8.7 at T0; 4.4 at T1; 3.3 at T2.

▪ Pustular lesions:
▪ T1: 43% reduction from T0 to T1
▪ T2: 80% reduction from T0 to T2
▪ mean values 2.3 at T0; 1.3 at T1; 0.45 at T2.
Results: efficacy

Measurement using SoftPlus

▪ T2: Seborrhea: 15% reduction from T0 to T2
▪ mean values 72.7 at T0 and 61.6 at T2

▪ T2: Hydration: 32% improvement from T0 to T2

▪ mean values 45.2 at T0 and 60 at T2
Results: tolerability
▪ After 4 weeks of treatment (T1) the tolerability of the treatment was considered:
▪ excellent according to 40% of subjects
▪ good according to 45% of subjects
▪ fair according to 15% of subjects.

▪ At 12 weeks (T2) it was:

▪ excellent according to 70% of patients
▪ good according to 25% of patients
▪ fair according to 5% of patients.

▪ No severe side effects were reported:

▪ 5% of patients complained about erythema and desquamation during the treatment, evaluated as
mild and transient.
RCM showed normalization of the honeycomb pattern, improvement
of infundibular hyperkeratinizazion and reduction of dermal
inflammation and exocytosis.
 Reduction of the tickened bright border
Hyperkeratotic follicle with thickened infundibula
bright border infundibula
Female, 25 yo – Microcomedonic ance.
GAGS score baseline: 8
GAGS score at week 12: 0 (clearance complete)
Male, 18 yo with papulo pustular acne and comedons of the face. Baseline, after 4
weeks and 12 weeks follow-up. GAGS score decreased from 16 to 5.
Female 23 yo. Microcomedonic acne of the front.
GAGS score at baseline: 7. GAGS score after 12 weeks of treatment: 1
Male 16 yo. Papulo-pustular
acne.
Baseline GAGS score 17
End of treatment GAGS score: 6
Conclusions
➢ Acne treatment, often for mild forms, before systemic agents, in young patients remains a
challenge
➢ The possibility of using a new topical formulation containing the most effective active
ingredients in acne, improves the dermatologist's therapeutic armamentarium.
➢ Our data indicate that this innovative topical medical device is effective, safe and well-
tolerated treatment for mild acne with a synergistic mode of action that inhibits
Cutibacterium acnes proliferation, reduces seborrhea while improving skin texture and
hydration.
➢ No risk of bacterial resistance.

➢ Furthermore, our results suggested that these studied compounds could be considered as
“maintenance treatment” after specific pharmacological treatment, even in more severe
types of acne.