MULTI-GENERATIONAL STOMACH SLIMMING SOLUTION. be inspired. reveal

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1 observe PHEOSLIM & PERILIPIN: MULTI-GENERATIONAL STOMACH SLIMMING SOLUTION be inspired reveal

2 NEW PHEOSLIM & PERILIPIN: MULTI-GENERATIONAL STOMACH SLIMMING SOLUTION BE INSPIRED A slimming agent for everyone. The effective slimming agent for mature women. Phyllacantha fibrosa Phyllacantha fibrosa belongs to the C y s t o s e i r a c e a e family, large brown algae that colonise rocky substrates just below the surface with a preferenceforareas of high turbulence. Solidly fixed to the rocks, Phyllacantha fibrosa, which is rough or even spiny to the touch, forms large tufts with its highly branched olive brown to red thallus, constantly battered by the waves. It forms dense clumps that serve as a refuge for numerous species of molluscs and crustaceans, and is also an important source of food for all of the herbivorous fauna. This brown seaweed is present throughout the year, but periodically regenerates its branches, which fall during the winter, leaving only the basal part visible. Highly sensitive to pollution, it is a good indicator of the quality of the environment. Codif Recherche et Nature harvests it in Brittany, in the turquoise waters of the Brehat archipelago. Belly fat is a preoccupation that affects every generation. Even though fat is preferentially stored on the thighs and buttocks in young women, the menopause and female hormones promotes storage on the belly. Not all generations experience the same difficulty in eliminating these abdominal curves. Recent studies have shown that standard lipolytic agents are less effective in mature women than in younger women. In response to the problem of fat in the stomach area, which is seen in young and more mature women alike, Codif Recherche et Nature has developed an exclusive slimming strategy with Pheoslim. OBSERVE Pheoslim has a dual action for a significant and lasting reduction in the volume of the abdominal belt: 1 - Inhibition of the formation of new mature adipocytes to limit the storage of fats and therefore the expansion of adipose tissue. 2 - Stimulation of lipolysis with the same efficacy in young women as in mature women. This multi-generational solution is made possible by the inhibition of Perilipin A, whose principal role is to protect lipid stores. WITHOUT PHEOSLIM WITH PHEOSLIM Nucleus Lipid droplet Perilipin A Lipolytic agent Lipolysis Lipolysis Lipolytic action : Lipolytic action : +++ Perilipin A can be found all around the lipid droplets. Acting as a protective shield, it limits the access of lipolytic agents to the fat stores and therefore limits lipolysis. Pheoslim inhibits the synthesis of Perilipin A, making the fat stores more accessible to lipolytic agents, for optimal slimming action. Its exclusive mode of action on Perilipin A gives Pheoslim a heightened and multi-generational slimming action. By facilitating the access of lipases to the fat stores whilst stimulating lipolysis, Pheoslim is the only lipolytic agent capable of stimulating the degradation of triglycerides in both young and mature women. Its inhibitory action on adipogenesis then prevents the formation of new adipocytes and therefore the storage of fats.

3 In vitro test: effect of 1% Pheoslim on the synthesis of new adipocytes in post-menopausal women Quantity of triglycerides stored (% of non-induced control) %* young woman model *p<,5 Student t Test +16% post-menopausal woman model The effect of hormonal variations in post-menopausal women Protocol : The cellular differentiation process was induced in cultures of pre-adipocytes containing high concentrations of oestradiol (young woman model) or low concentrations of oestradiol (post-menopausal woman model). maturation was assessed by measuring the quantity of stored triglycerides (the lipid stores were stained using Red Oil). The female hormone oestradiol, when synthesised in high concentrations, inhibits the differentiation of pre-adipocytes of the waist region into mature adipocytes, thus limiting the storage of fats in this zone. In post-menopausal women, the low concentration of this hormone is no longer capable of limiting the maturation of pre-adipocytes. This results in an increase in fat storage and an expansion of adipose tissue. Quantity of triglycerides stored (% of non-induced control) % post-menopausal woman without Pheoslim +48%* post-menopausal woman with 1% Pheoslim Effect of 1% Pheoslim on the synthesis of new adipocytes in post-menopausal women Protocol : The cellular differentiation process was induced in cultures of pre-adipocytes containing low concentrations of oestradiol (post-menopausal woman model) in the presence or absence of 1% Pheoslim. maturation was assessed by measuring the quantity of stored triglycerides (the lipid stores were stained using Red Oil). By inhibiting the formation of new adipocytes, 1 % Pheoslim decreases the expansion of adipose tissue by 58% in post-menopausal women. The use of Pheoslim counteracts the negative effects of a low level of oestradiol in post-menopausal women. *p<,5 Student t Test In vitro test: effect of 1% Pheoslim on Perilipin A Perilipin A NEW The notion that proteins cover the cytosolic surface of lipid droplets and play a crucial role in the regulation of the metabolism of neutral lipids came with the discovery of Perilipin A in the lipid droplets of adipocytes by the Constantine Londos laboratory (Brasaemle DL., 27). Perilipin A is a protein that coats the lipid droplets of adipocytes (Greenburg AS et al., 1991). It forms a protective layer against the lipases of the organism, such as hormone-sensitive lipase (Wong K., 2), which degrade the triglycerides into glycerol and free fatty acids via a process known as lipolysis. Nucleus Lipid droplet Perilipin A Lipase

4 Effect of 1% Pheoslim on Perilipin A Protocol : Cultures of mature adipocytes are brought into contact with 1% Pheoslim for 24 h. Following the 24 h incubation, the rate of expression of Perilipin A is assessed using quantitative PCR. Expression of Perilipin A (% of control without Pheoslim) WithoutPheoslim -39% NEW 61 With 1% Pheoslim Culture of adipocytes without Pheoslim Immunolabelling of Perilipin in green Culture of adipocytes with 1% Pheoslim Immunolabelling of the Perilipin in green 1% Pheoslim decreases the expression of Perilipin A in mature adipocytes by 39% thus promoting the access of lipases to the large lipid droplets. The immunological labelling of Perilipin A shows, other than a decrease in the expression of the protein, a decrease in the size of the adipocytes. This action indicates that lipolytic activity has been stimulated thus enhancing slimming action. In vitro test: effect of 1% Pheoslim on the natural inhibitors of lipolysis % Inhibition Protocol : The effect of Pheoslim was tested on the expression and / or fixation on their receptors of the natural inhibitors of lipolysis, which are as follows: Phosphodiesterase III (PDE III), the fixation of adrenaline to its alpha receptor (alpha A), the fixation of neuropeptide Y to its receptor (NPY). From 1%, Pheoslim inhibits in a dose-dependant manner: - the activity of PDEIII; by up to 82% - the fixation of Adrenalin to its alpha receptor; by up to 42% - the fixation of Neuropeptide Y to its receptor; by up to 4% 2 1 1% 2% 3% 4% Pheoslim (%v/v) PDEIII alpha A NPY 5% This decrease in the natural inhibitors of lipase induces an increase of +115% of camp. Combined with a decrease in the expression of Perilipin A, the results lead to expect an optimal lipolytic activity for Pheoslim from 1%. In vitro test: Lipolytic effect of 1% Pheoslim on adipocytes taken from the abdominal region. The activity of lipolytic agents with age The efficacy of standard lipolytic agents such as theophylline and isoproterenol decreases with age in women. The adipocytes become increasingly refractory to lipolysis with age, which explains the difficulties encountered in treating these cells and the low efficacy of cosmetic products in subjects over 5 years of age. Response to lipolysis produced by theophylline Effect of 1mM theophylline on the lipolysis of adipocytes as a function of the age of the donor Response to lipolysis produced by isoproterenol (% control) Effect of 1µM isoproterenol on the lipolysis of adipocytes as a function of the age of the donor

5 The lipolytic efficacy of 1% Pheoslim as a function of age, on adipocytes isolated from the abdominal region. Protocol : Cultures of mature adipocytes taken from abdominal plasties in women aged between 35 and 51 years are incubated in the presence or absence of 1% Pheoslim. The lipolytic efficacy was assessed by measuring the concentration of NEFA (Non-Esterified Fatty Acids) released into the culture medium by lipolysis. Lipolytic activity (% of control without Pheoslim) Lipolytic efficacy of 1% Pheoslim on mature adipocytes between 35 and 51 years of age year old adipocytes Without Pheoslim year old adipocytes With 1% Pheoslim Evolution of the lipolytic activity (%) Comparative efficacies of different lipolytic agents as a function of age Age of the adipocytes 1% Pheoslim 1mM Theophylline 1µm Isoproterenol By inhibiting Perilipin A, and decreasing the quantities of natural inhibitors of lipolysis, 1% Pheoslim stimulates the lipolysis of fat stores by +297% in adipocytes from 35 years and by +358% in adipocytes from 51 years. Compared with standard lipolytic agents, only Pheoslim is capable of increasing the lipolytic activity with age: +21% between 35 and 51 years, whilst there is a decrease of -48% and -47% with Theophylline and Isoproterenol respectively. REVEAL Clinical test: slimming effect of 1% Pheoslim on the volume of the abdominal belt Protocol : 17 volunteers aged between 5 and 55 years 1% Pheoslim 2 applications per day for 28 days on the belly Study of the variations in the volume of the abdominal belt by fringe projection After 28 days of twice daily application, 1% Pheoslim significantly reduces the volume of the abdominal belt by an average of -4.3% (p <.5 Student t test) and up to 18.3%. Pheoslim inhibits the formation of new adipocytes and thus the expansion of adipose tissue. The inhibition of Perilipin A, combined with a stimulation of lipolysis, gives Pheoslim an exclusive and original slimming action in women of all ages and notably in mature women who are usually confronted with the loss of efficacy of standard lipolytic agents with age. Pheoslim visibly and significantly reduces the volume of the abdominal belt. Marine origin Hydrosoluble active ingredient in-vitro test in-vivo test ECOCERT validation

6 PHEOSLIM: MULTI-GENERATIONAL STOMACH SLIMMING SOLUTION Cosmetic activities: Inhibition of Perilipin A to facilitate the access of lipases to the triglyceride stores. Decrease in the expression of the natural inhibitors of lipolysis: Phosphodiesterase III, alpha-adrenergic receptor, neuropeptide Y receptor. Enhanced lipolytic action in young and mature women Significant reduction in the volume of the abdominal belt INCI name Recommended % of use Pheoslim: Water (and) Phyllacantha fibrosa extract (and) Phenoxyethanol Pheoslim G: Glycerine (and) Water (and) Phyllacantha fibrosa extract Pheoslim: 1% Pheoslim G: 2% Technical department : Codif Recherche & Nature infotech@codif-recherche-et-nature.com Commercial department: Codif Recherche & Nature commercial@codif-recherche-et-nature.com 7, rue du Commandant l Herminier - BP Saint-Malo cedex - FRANCE Tel : Fax : CODIF Recherche et Nature is committed to sustainable development. All our wastewater is processed and purified using filtrating gardens. A succession of airtight horizontal and vertical filters is used to depollute wastewater by the roots of plant species chosen for their draining properties. Iris, water mint, flowering rush, willows etc now form part of the image of the brand which is recognized for its commitment to the preservation of natural resources RPDOC86GB