BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS

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Offers dermatologists, practitioners and beauty professionals a wide range of depigmentation products, providing treatments uniquely formulated according to the type of hyperpigmentation, skin type and the part of the body affected. INNOAESTHETICS laboratory recommends consulting a specialist before starting any depigmentation treatment. Only a qualified professional will be able to provide a diagnosis to determine the best type of treatment based on the type of hyperpigmentation, its location and the patient s skin type. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 3

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SPECIFIC DEPIGMENTATION TREATMENTS Amongst its extensive range of medical-aesthetic treatments, INNOAESTHETICS laboratory offers a full range of products developed to treat one of the most common dermatological problems: skin hyperpigmentation. More and more people are being affected by dark patches on their skin, whatever the colour of their skin. While just 10% of the American population is affected by this condition, this percentage rises to 40% in Asia and South America. In Europe, 20% of women over 25 have some degree of hyperpigmentation, which increases significantly as they age. One in three women over the age of 40 suffer from this skin disorder, a figure that can rise to 90% among women over 50. To respond to the needs of professionals and to this growing demand among their patients, INNOAESTHETICS has developed MELINE. A brand that specialises in the treatment of hyperpigmentation. MELINE is an effective alternative to other, more invasive techniques, which may damage the skin and lead to a rebound effect and post-inflammatory hyperpigmentation. In addition, it delivers a more comprehensive treatment compared with other methods that merely provide a corrective action, such as laser and IPL treatments. Unlike these treatments, MELINE acts at the cell level, going to the root of the pathology. By regulating the uncontrolled growth of melanocytes, MELINE products not only eradicate dark patches, but also effectively prevent their reappearance. MELINE is unique among topical depigmentation treatments on the market because it tackles hyperpigmentation in a specific manner. The range comprises 17 products that can treat any kind of melanic or melano-hematic dark patches, these include products that have been exclusively formulated to treat solar lentigo and others for melasma/chloasma. Additionally, to achieve a greater therapeutic effect, the laboratory also offers depigmenting products specifically developed for either white and Caucasian skins (phototype I III) or for ethnic skins (phototype IV VI). MELINE also includes products for particularly delicate areas, such as the genital and perianal areas. The range will soon be extended to include depigmentation products for other specific parts of the body that are subject to constant friction and where pigment deposits often form, such as the under-arms, elbows and knees. MELINE will also shortly be introducing a treatment specifically for patients suffering from acanthosis nigricans. MELINE provides integrated solutions which combine professional treatments with home care products, which act together in synergy. For ease of use, the product packaging is numbered to indicate the order in which they should be applied according to established protocols. In addition to eliminating between 90 and 95% of the hyperpigmentation, as proven in several clinical trials, the MELINE products significantly improve the quality and aspect of the skin, brightening it and reducing fine lines and imperfections. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 5

1- Specific depigmentation treatments for different skin types There is a wide variety of skin types, each with their unique characteristics. Depending on its phototype, the skin can react in different ways to endogenous factors and to exogenous factors such as the sun s rays. The response to an injury such as inflammation or irritation manifests differently on lighter skins and on darker skins. Additionally, each skin phototype has a tendency towards different clinical profiles. Dyschromia and hyperpigmentation, for example, are some of the most common dermatological skin disorders seen on IV-VI skin types due to their higher concentration of melanin. Managing the problem in this skin type is more complex than it is with Caucasian skin and may pose a considerable challenge in some cases. On the other hand, skin types I, II and III burn more easily and are more susceptible to aging. To ensure the success of a pigmentation removal treatment, it is as important to take account of the patient s skin type as it is to identify the type of hyperpigmentation and its location either on the epidermis, dermis or a mixture of both. The MELINE products are formulated to suit to the particular characteristics of each skin type. The range therefore includes exclusive treatments for low skin phototypes, from I to III, and high skin phototypes, from IV to VI. To test the safety and therapeutic efficacy of its treatments, INNOAESTHETICS has conducted several clinical trials on patients of different ethnic groups and with different skin phototypes, in partnership with hospitals, practitioners, beauticians and dermatological centers in a variety of countries. 6

2- Specific depigmentation treatments for different types of hyperpigmentation The dark spots caused by chronic sun exposure can be of two types: lentigo or melasma. Melasma, which generally affects women, and especially those with darker skin types, primarily appears as a result of hormonal changes, or after taking photosensitive medication or contraceptives. Melasma in men is normally associated with hereditary factors. This type of hyperpigmentation has a diffuse appearance and is usually present on the forehead, cheeks, upper lip and chin. Lentigines, usually caused by the effects of ultraviolet light, also appear due to the skin s intrinsic ageing process. These are localised, well-defined spots that appear mainly on the forehead, chest, hands, arms, shoulders and back. Identifying the type of hyperpigmentation and at what histological level the melanic pigmentation is located, forms the basis for all depigmentation treatments. Since the same product cannot be used to treat every type of hyperpigmentation, the laboratory s R&D department has developed products that are specifically formulated to treat lentigines and others to target melasma and chloasma. Each product contains a specific combination of certain active ingredients in specific concentrations. For example, since the corneal layer of ethnic skins is thicker, and they have more eumelanin, the level of cytotoxicity of the treatment formulas for darker skin types is lower compared with those for Caucasian skin, thus, undesirable effects are avoided, as are the pigmentary rebounds, so characteristic of dark skins. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 7

Treatments for Melasma and Chloasma 1- Patients with I-III skin types PROFESSIONAL TREATMENT 01 Caucasian skin Chemical dermabrasion creamy mask with Azelaic acid, Tranexamic acid, Arbutin, Kojic acid, Lactobionic acid Sodium hyaluronate, Retinal and Phenylethyl Resorcinol POST PROFESSIONAL HOME TREATMENT 02 Caucasian skin day Concentrated serum that reduces pigmentation and melanin deposits. Apply in the morning. 02 Caucasian skin night Emulsion that delays the appearance of pigmentation. It Inhibits tyrosinase enzyme expression and melanin synthesis. Apply at night. 8

Para melasma y cloasma 2- Patients with IV-VI skin types PROFESSIONAL TREATMENT 01 Ethnic skin Concentrated serum creamy mask with Mandelic Acid, Ascorbic acid, Tranexamic acid, Phytic acid, Pyruvic acid, Salicylic acid, Retinal and Sodium Hyaluronate.. POST PROFESSIONAL HOME TREATMENT 02 Ethnic skin day Concentrated serum that improves and delays the appearance of skin pigmentation and controls melanin synthesis. Apply in the morning. 02 Ethnic skin night Emulsion that improves and delays the appearance of pigmentation and inhibits tyrosinase enzyme expression and melanin synthesis. Apply at night. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 9

Treatments for lentigines PROFESSIONAL TREATMENT POST PROFESSIONAL HOME TREATMENT 01 Spot Treatment kit for solar lentigines and hyperkeratosis applied in 2 steps: Step 1: Solution containing Azelaic acid, Tranexamic acid, Phenylethyl Resorcinol and Sodium Hyaluronate. Step 2: Mask formulated with Pyruvic acid, Salicylic acid, Sodium Hyaluronate. 02 Spot Solution in gel form that helps to remove epidermal melanin pigment. Apply to the affected area in the morning and at night. 10

Effective formula developed based on clinical studies To generate the maximum synergy between their active ingredients and to assess their therapeutic effects, the laboratory performed several clinical trials. In vitro studies: Microscopic images from an in vitro study conducted with MELINE 02 CAUCASIAN SKIN DAY showing a 41.65% inhibition of melanin synthesis in human melanoma cells exposed to the product compared with untreated cells. Negative control: Untreated cells Positive control: Cells treated with Hydroquinone (reference active ingredient in the treatment of hyperpigmentation). The disintegration of the melanin pigments is clear.. Cells treated with 02 Caucasian skin day with a concentration of 0.01mg/ml. A clear reduction in the intracellular melanin pigments is noted. Cells treated with 02 Caucasian skin day with a concentration of 0.002mg/ml. In the photo above it is possible to observe the product effectiveness although its concentration is lower. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 11

Patient 2 Clinical trials 1- Patients with melasma Bellow, photos of patient with skin type III treated with MELINE 01 CAUCASIAN SKIN following a protocol of 2 professional treatment sessions at the clinic and 8 weeks of home maintenance treatment with MELINE 02 CAUCASIAN SKIN DAY and MELINE 02 CAUCASIAN SKIN NIGHT. Patient 3 Before After In the photos, taken with a polarized light, a significant reduction in the pigment deposits can be observed (which contributes to a more even skin tone), as well as an improvement in its appearance. Before After Patient 1 Patient 4 Before Before After After Before After Photos of patients with darker skin types treated with MELINE ETHNIC SKIN, following a protocol of 2 professional treatment sessions at the clinic and 16 weeks of home maintenance treatment with MELINE 02 ETHNIC SKIN DAY and MELINE 02 ETHNIC SKIN NIGHT. A significant improvement in the pigmentation is observed in both cases. 12

2- Patients with lentigines The photos below show the gradual improvements obtained with MELINE 01 SPOTS. As can be seen in the photos, a crust forms on the second day. On day 7, the crust starts to fall. On day 30, the lentigo has almost completely disappeared. Day 1 Day 4 Day 6 Day 30 Day 60. Final Outcome The results were confi rmed by a statistically signifi cant reduction in the mean melanin score recorded using a Mexameter of T2 (322.967) compared to T0 (358.6125) and in the normal surrounding skin of T0 (300.95) and T2 (304.65) (p <0.02). BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 13

3- Specific depigmentation treatments according to the area to be treated Given that the characteristics and the sensitivity of the skin is not the same in every part of the body, the MELINE range also offers pigment removal treatments for specific regions, such as intimate areas. Anal and vulva whitening, one of the most in-demand aesthetic treatments in the US, is now rapidly gaining popularity across Europe. Many factors affect the darkening of these areas. They are constantly subject to traumatic actions like the use of toilet paper, exposure to damp conditions, iron in menstrual blood and also to tightly fitting underwear. Pubic hair waxing, which has become widespread in recent years among both men and women, has also contributed to more people being affected by hyperpigmentation in the genital region. Whitening treatments in the vulva region must be extremely safe because the mucous membrane of the labia can generally become more pigmented and is much more susceptible to irritation and burning than other areas of the skin. MELINE 01 INTIMATE therefore contains mandelic acid, which permits the exfoliation of the corneal layer and provides an antimicrobial effect. The high molecular weight of this acid limits its degree of penetration which means it is less irritating. Its presence in the formula also controls the penetration of other more potent depigmenting acids. One of these is tranexamic acid, which inhibits plasminogen and deactivates tyrosinase. Another is lactobionic acid, which slows down metalloproteinase and strengthens the skin s protective barrier. The laboratory will soon be launching products for other specific parts of the body that are subject to constant friction and where pigment deposits often form, such as the under-arms, elbows and knees. MELINE will also shortly be introducing a treatment specifically for patients suffering from acanthosis nigricans. 14

Treatment for intimate areas PROFESSIONAL TREATMENT 01 Intimate Antioxidant keratolytic solution with Mandelic acid, Tranexamic acid, Lactobionic acid, Salicylic acid, Retinal and Sodium Hyaluronate. POST PROFESSIONAL HOME TREATMENT 02 Intimate Concentrated gel that effectively reduces melanin synthesis and subsequently reduces pigmentation in the genito-anal region. Apply at night for 60 days. BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 15

MODE OF ACTION The MELINE products are formulated with ingredients that act upon every stage of melanogenesis. Each acts on a different level to inhibit melanin production both during and after treatment to achieve a corrective and regulating action. This way the MELINE products not only significantly reduce existing dark patches but also prevent their reappearance and considerably reduce the risk of new dark patches forming. 16

INTEGRATED DEPIGMENTATION TREATMENTS MELINE includes 2 distinct lines: a line of professional products that are used in the clinic as a shock treatment, and a maintenance range for use at home. Both lines have been formulated so that their active ingredients have a synergic effect, thus producing the most effective and long-lasting results. In addition to the treatment products, the professional line includes 2 coadjuvant products to maximise the efficacy of the overall treatment: MELINE 00 PREP, a cell depolymerising solution that increases the skin s permeability. MELINE 01 ID, a transdermal release solution whose active ingredients produce a potent antioxidant and anti-inflammatory action. It has a melanocyte synthesis inhibitory effect as well as inhibiting the tyrosinase enzyme. Coadjuvant products for professional and home treatments PROFESSIONAL TREATMENT PREP Cellular depolymerising topical solution that reverses the polarity of the skin and increases its permeability. ID Transdermal release solution to aid depigmenting treatments BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 17

POST PROFESSIONAL HOME TREATMENT Moist Balances the skin hydration. Integral cell activity renewal. Apply in the morning and at night. B.B. Cream SPF 30+ Sunscreen for use with hyperpigmentation treatments. Imperfection correction for skin types I - IV. Apply 2 to 3 times a day according to skin s need. Pigment Home Mask Potent ingredients with depigmenting and antioxidant activity. Boosts professional pigmentation removal treatments. Apply once a week. 18

EASY TO USE TREATMENT PROTOCOLS To maximize the effectiveness and therapeutic response of its treatments, the laboratory has elaborated specific application protocols for each one. In addition, for ease of use, the packaging of the MELINE products are numbered according to their function and the order in which they are to be applied. The design of the packaging also helps to distinguish at first glance between the professional and home-use products. The products for professional use have a red line, while the line on the home care products is grey. Order the products are applied and their: 00: Skin permeability control 01: Professional treatment 02: Post-professional home treatment 03: Recovery and hydration 04: Imperfection protection and control 05: Home treatment enhancement BRAND SPECIALISING IN THE TREATMENT OF DARK SPOTS 19