Rapidly reducing the inflammation of acne lesions and scars optimises patients' compliance with acne treatments. Pathophysiology

Transcription

1 Study of the benefit of Cytolac, a moisturising cream formulated with Centella Asiatica, used as a monotherapy to treat the retentional, inflammatory and scarring lesions caused by moderate acne S. BECHAUX 1, I. EGASSE-BROCA 2, M. FILBET 3, I. GALLAY 4 F. ROUDIL 5, G. ROSTAIN 6, G. TOUBEL 7, B. TACK , rue Someiller Annecy , avenue du Général Leclerc Paris bis, boulevard Alsace-Lorraine Pau bis, place Saint-Bénigne Dijon , place de la République Fos-sur-Mer , rue Châteauneuf Nice , place des Lices Rennes - 8 6,rue de la Chaussée Ferrée Caen Rapidly reducing the inflammation of acne lesions and scars optimises patients' compliance with acne treatments. Pathophysiology Acne is a disorder of the pilosebaceous follicle that progresses in 3 stages. The first stage is stimulation of the sebaceous gland, causing hyperseborrhoea, which begins at puberty. This stimulation is linked to hypersensitivity of the sebaceous gland receptors to androgens. The enzymatic make-up of the receptors is highly variable from one individual to another, explaining the clinical and therapeutic differences encountered. Sebaceous glands also possess receptors to neuromediators (substance P and alpha-msh), explaining why acne break-outs can occur in response to stress. The second stage consists of the formation of microcomedones subsequent to a disorder in the differentiation and proliferation of keratinocytes, promoted by changes in sebum composition, interaction with cytokines and the expression of certain integrins. The third stage is inflammation of the sebaceous gland. This plays an early and dominant role in the genesis of the disease, particularly via the release of pro-inflammatory substances due to Propionibacterium acnes (metalloproteinases, lipases et interleukins). Propionibacterium acnes itself behaves like a super-antigen, by activating T lymphocytes. Treatment therefore needs to address three problems: reduce seborrhoea, stress and the psychological impact of this distressing skin condition, by quickly reducing acne lesions. Hence it is essential to reduce the formation of microcomedones and inflammation by reducing the presence of Propionibacterium acnes. The objective of this study was to demonstrate and confirm the efficacy of Cytolac on these 3 stages that have already been observed clinically. Composition of Cytolac cream Cytolnat (1) offers physicians access to Cytolac, its specific skincare treatment for oily, blemished skin. Cytolac is an oil-in-water (O/W) emulsion, with a composition that combines: - an aqueous phase (W) containing: a filmogen - squalane - that forms an external protection over blemishes; moisturising and emollient ingredients (white petrolatum, allantoin), which create a moist environment, favourable to skin healing; - two surfactants, one ionic - triethanolamine stearate - and the other nonionic - glyceryl stearate - with mild emulsifying properties, aiding the elimination of sebaceous secretions from the follicles. These surfactants trigger activation of the skin's microcirculation, with an influx of polynuclear neutrophils that help sterilise the zone to be treated. In addition, the bacteriostatic effect of the triterpenes contained in purified extracts of Centella asiatica have been demonstrated in vitro on Propionibacterium acnes, Staphylococcus aureus and group B Streptococcus (2); - an oily phase (O) containing polyunsaturated vegetable oils (Avocado oil and Grape seed oil), which act as a sebum solvent making it easier to eliminate it, while also preventing the formation of blackheads; 1

2 - an active ingredient - titrated extract of Centella asiatica (TECA) - for which the decongesting and healing effects have already been clearly demonstrated (3, 4). A recent change in the INCI naming system for Centella asiatica extracts has led to them being named on the basis of the purity and quality of the extracts. Hence the TECA titrated extract contains a mixture of 40% asiaticoside and 60% madecassic acid and asiatic acid. This very pure and highly effective extract has been selected as an ingredient for Cytolac cream. The triterpenes in Centella asiatica boost antioxidants in the cells and increase fibroblast and extracellular matrix synthesis (5-7) (Tab. I, II; Fig. 1). We thought it would be interesting to study the healing, anti-inflammatory and anti-acne activity of Cytolac cream via this new clinical study conducted among dermatologists. The number of component lesions of the acne, the different skin qualities, the tolerance and the acceptability of Cytolac cream were assessed. Tab I : characterstics of the plant Fig.1 : chimical structure of genins Tab II: INCI for Centella asiatica Extract Material and methods This was an open, multicentre study conducted from January 2006 to May 2006 among 8 dermatologists across France. The protocol for this study was approved by the Ethics Committee of Grenoble Teaching Hospital on 4 January 2006 and by the CNIL (French data protection body) (No ). Inclusion criteria The main inclusion criteria was moderate polymorphic acne of the face, with at least 20 component lesions of acne, such as microcysts (whiteheads), comedones (blackheads), papules, pustules or scars. Patients were not to have been treated with isotretinoin within 6 months prior to inclusion or to have used any other acne treatments. For women using combined oestrogen/progestin contraception, this must have been begun at least 6 months previously. Exclusion criteria Patients presenting an active skin disease of the face, known intolerance to any of the ingredients in the cream being studied or with acne judged to be severe were excluded. 2

3 Method of use of the cream Cytolac in acne After they had signed an informed consent form, patients were given an instruction leaflet concerning the use of the study product. Their skin cleansing routine remained unchanged throughout the study. Cytolac cream was to be applied morning and night to the face, on slightly damp skin, for 3 consecutive months, with clinical assessment performed by the investigator at inclusion (D0), at 1 month (D30), at 2 months (D60) and at 3 months (D90). No half-face comparative study versus a reference topical product or versus an excipient was performed. Efficacy assessment criteria The assessment criteria were purely clinical and qualitative, evaluated by the same investigator at D0, D30, D60 and D90. An assessment of the type and severity of the acne was made by performing a clinical count of each component lesion: whiteheads, blackheads, papules, pustules and scars. Clinical items concerning skin hydration, seborrhoea, erythema, scar depth and skin grain appearance were assessed on a scale of 0 to 10. There were no quantitative measurements using sebumetry or sebutape to measure follicular sebaceous secretion. There were no skin relief studies using silicone skin imprints that would have made it possible to assess the tightening up of dilated pores, the improvement in roughness and the improvement in scar depth. In addition, to avoid complicating the clinical study, no photographs were requested, since to be able to interpret these they would need to have been standardised in each dermatology practice, with the use of the same digital camera and framing, lighting and position standardised for each photo. As regards compliance with twice-daily application, this was assessed on the basis of three levels: good (twice daily), moderate (once daily) or poor, with indication of the number of days without application. The overall assessment of the investigator and the patient was evaluated at the end of the study, using a 4-point scale: nil, slight, satisfactory, very satisfactory. Tolerance assessment criteria The tolerance was assessed by the patient and the investigator at D30, D60 and D90 on the basis of different items (erythema, oedema, scaling, itching, burning sensations, stinging, tightness) and according to an increasing intensity scale (none, mild, moderate, severe). The overall assessment of the investigator and the patient was evaluated at the end of the study, using a 4-point scale: poor, quite good, good or very good. Cosmetic acceptability assessment criteria The cosmetic acceptability of the study product was assessed by the patient at the end of the study with respect to ease of application and ease of absorption, soothing effect and pleasant character of the texture and odour, or otherwise. Results Description of the study population The sample of the population studied was represented by 44 subjects meeting the inclusion criteria. This population consisted of 34 female subjects (77%) and 10 male subjects (23%). The mean age was 23 years. Type and severity of acne An assessment of the type and severity of the acne was made by performing a clinical count of each component lesion: whiteheads, blackheads, papules, pustules and scars, ranging from 0 to over 50 components. Table III summarises the evolution in mean number of lesions per patient, as recorded at the visits on D0, D30, D60 and D90. Tab III : Evolution in the mean number of lesions per patient 3

4 Figure 2 illustrates the reduction in lesions, in particular whiteheads (- 40% at D60), papules (- 32% at D30) and blackheads (- 16% at D30, - 30% at D60). The severity of scars reduces by 15%. Fig.2 : Evolution in the mean number of lesions per patient Clinical efficacy A subjective clinical assessment was performed by the physician on the basis of the evolution in the following parameters: - skin hydration: very dry skin = 0, moisturised skin = 10; - seborrhoea: very abundant = 0, normal = 10; - erythema: nil = 0, intense = 10; - scar depth: nil = 0, very deep = 10; - skin grain: soft = 0, very rough = 10. Table IV summarises the mean evolution in clinical assessment criteria per patient on a scale of 0 to 10, at the visits on D0, D30, D60 and D90. Tab IV. : Clinical assessment criteria Fig.3 : clinical efficacy A rapid and marked improvement in skin hydration and normalisation of seborrhoea are observed. Likewise, erythema reduces by 60% at D60 and the skin grain is refined. The results with respect to scar depth are less spectacular given the starting point at D0 (Fig. 3). Assessment of tolerance Tab. V : Evolution of the studied parameters Table V gives the evolution in the parameters studied and rated on a scale of 0 (no symptom) to 3 (severe symptom) as assessed by the investigating physician and the patient at the visits on D0, D30, D60 and D90. The results are practically identical between the physician and the patient.. 4

5 The very marked improvements in erythema (- 85% at D60), scaling (- 92% at D60), itching (- 90% at J60), burning sensation, stinging, tightness (- 96% at D90) can be noted (Fig. 4). Fig.4: Assesment of tolerance Assessment of compliance Cases in which the patients used the treatment up to D90, with good (twice daily application) or moderate (once daily) compliance were used for the assessment. Around fifteen cases could not be retained, particularly in the teenage population or as a result of the patient being lost to follow-up. However, analysis of the evolution in the various criteria or parameters over the periods available for the cases having stopped before D90 reveals results consistent with the cases retained for the same periods. The study results demonstrate that good compliance with treatment is essential to achieve satisfactory and lasting results. Cosmetic qualities Table VI details the patients' assessment at D90 on the basis of 5 cosmetic acceptability criteria rated 0 for no or unpleasant or 1 for yes or pleasant. The table gives the mean score out of 1. Cytolac cream obtains excellent scores for the various cosmetic criteria (Fig. 5). Tab VI. : Acceptability criterias Fig.3 : comsetic quality evaluated to D90 The score concerning ease of absorption would have been higher if all the patients had been careful to follow the instructions for use recommending application to slightly damp skin. 5

6 Discussion This study demonstrated the efficacy of Cytolac cream on retentional and inflammatory lesions, with a 40% reduction and more in their number in 2 to 3 months: this result is very encouraging for this product considered to be a cosmetic. Furthermore, good results were obtained on chronic acne having been resistant to conventional anti-acne treatments. The lesion healing time is markedly reduced. Finally, the very marked reduction in erythema and tightness is encouraging for patients. During this study, new indications were reported: there was a highly satisfactory case concerning cysts between the breasts for which all treatments had failed. The cream makes skin microsurgery sessions easier, it treats shaving rash and it is greatly appreciated after leg hair removal. Conclusion The study concerned the use of Cytolac as monotherapy in moderate acne. The results obtained are satisfactory, particularly for late-onset acne, and demonstrate significant reductions in the component lesions of acne with, at D60, reductions of 40% in whiteheads, 30% in blackheads, 40% in papules, 33% in pustules. Cytolac will also be useful in addition to anti-acne treatments such as isotretinoin since it rapidly reduces inflammatory lesions and will help improve patients' compliance with their treatment. References Loiseau A et al. Evidencing the anti-microbial properties of Centella asiatica. Monographie interne Bayer Santé Familiale, Division Serdex, Shukla A et al. Asiaticoside-induced elevation of antioxidant levels in healing wounds. Phytother Res 1999 Feb ; 13 : Baspeyras M et al. Traitement des lésions pigmentaires et vasculaires cutanées par laser. Évaluation de l efficacité et de la tolérance du Cytolnat Centella crème en soin post opératoire à visée cicatrisante. Real Ther Dermato-Venerol 2004 ; 139 : Marquart FX et al. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur J Dermatol 1999 ; 9 : Anti-microbial properties of Centella asiatica. Bayer Santé Familiale, Division Serdex, Effet anti-inflammatoire du composé asiaticoside sur kératinocytes en monocouche induction par le PMA. Bayer Santé Familiale, Division Serdex,