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Technical File

DRIELINE®

Active ingredients

Skin Defence System

Highly purifi ed ß-glucan-Reinforces skin defences and skin renewal

Technical file DRIELINE®

Lucas Meyer Cosmetics Place de la Cité, Tour de la Cité, 2600 boul. Laurier, #900, Québec (Québec) G1V 4W2 Canada

www.lucasmeyercosmetics.com

CONTENTS

DRIELINE

A HIGHLY PURIFIED NATURAL ACTIVE INGREDIENT ................................................... 3

A LITTLE HISTORY ..................................................................................................................................... 4 DOUBLE ANTI-AGEING ACTION ................................................................................................................... 7

EFFECTIVENESS: THE ACTIVE ANTI-AGEING COSMETIC............................................................. 10

DRIELINE® STIMULATES THE PRODUCTION OF IL-1 ................................................................................. 11 INCREASED SYNTHESIS OF RNA IN THE GENOMIC RESEARCH ................................................................... 12 STIMULATION OF THE ANTI-MICROBIAL ACTION OF THE KERATINOCYTES ..................................................... 15 PROTECTION OF LANGERHANS CELLS AGAINST THE HARMFUL EFFECTS OF UVB ....................................... 16 CLINICAL ANTI-INFLAMMATION ACTION OF DRIELINE® .............................................................................. 20 ACTIVATION OF COLLAGEN SYNTHESIS ..................................................................................................... 23

CLINICAL EFFICACY.............................................................................................................................. 24

STIMULATION OF HEALING ....................................................................................................................... 25 NEW CONSUMER TEST ON STRETCH MARKS ............................................................................................. 34

DRIELINE, HOW TO USE IT ............................................................................................................... 35

COSMETIC USE ....................................................................................................................................... 36 RECOMMENDATION OF USE ..................................................................................................................... 36 INDICATIVE FORMULA............................................................................................................................... 37

BIBLIOGRAPHY ..................................................................................................................................... 38

http://www.lucasmeyercosmetics.com/




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DRIELINEA HIGHLY PURIFIED NATURAL ACTIVE INGREDIENT

DRIELINE is a highly purified natural extract of baker's yeast membrane, scientifically known by the name of Saccharomyces Cerevisiae.

Saccharomyces Cerevisiae is cultured to obtain a sufficient biomass, which is then purified. The yeast cells thus separated from their culture medium are subjected to lysozyme enzymes, to separate the different constituents from the walls. These are then "cleaned" to obtain a "pure" fraction of β-glucopyranose. Thanks to this biotechnology, the polysaccharide consisting of repeated units of β-1-3-glucopyranoses has an average molecular weight of 240,000 daltons and does not contain any residual monomer.

Molecular weight = 240 KD

This "sentry molecule", functioning by mimicry of action, reinforces the skin's natural defences, providing effective and permanent protection.

DRIELINE is used in cosmetic and dermal-cosmetic products for the prevention of ageing





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A little history Saccharomyces Cerevisiae has played an essential role in the production and preservation of food for more than 8000 years. Its remarkable contribution to the appearance and survival of the human species is due, among other things, to its power to ferment glucose and transform it into ethanol and carbon dioxide. Not only still used daily today in the brewing and baking processes, yeast, a eukaryotic unicellular organism, is a very powerful biological research model. This marvellous yeast is a unique living system, the study of which has revealed numerous secrets useful to mankind well beyond mere daily food requirements. Legend tells us that more than ten thousand years ago, a farmer in Mesopotamia discovered that seeds had germinated in water and developed a strange taste. He woke up the next day having made two of the major discoveries for humanity: bread and wine. But today, after scientists from throughout the world have worked on sequencing its genome, Saccharomyces Cerevisiae still guards its secrets. The very heart of the life of Saccharomyces Cerevisiae has been cut open and identified, yet its properties nevertheless remain mysterious… An extremely resistant structure The wall of Saccharomyces Cerevisiae contains (1-3)-beta-glucans, which are alcalo-soluble, and which serve as precursors for the completely insoluble (1-3)-beta-glucans. Certain theories (Hartland, 1994) suggest that the insolubility of the glucans could be due to chitins, rendering the yeast insensitive to hypo-osmotic shocks and thus contributing to the mechanical strength of the organisms. Resistance transformed into biological properties In 1900, Von Dungen proved that baker's yeast interacts with the serum proteins involved in the destruction of infectious organisms. Later, Pillermer and Ecker in 1941 found that the active fraction of yeast was the insoluble part of the wall of the yeast. Because the sole insoluble components of the wall are the beta-glucans, this class of polysaccharides was the subject of special research. They are non-toxic, particularly well tolerated, chemically defined and biological initiators for adjusting the defence mechanisms of the higher organisms. The dominant biological effect of the glucans is their involvement in activating the macrophages, cells at the heart of the immune regulating system. The demonstrated immuno-pharmacological properties of glucans are:

• Increased resistance to bacterial, viral, fungal and parasitical infections • An influence on the haematopoietic activity of the bone marrow • Increased metabolic and functional activity of the cells in the reticuloendoplasmic system • Stimulation of the cellular effectors of the immune system (therefore "natural killers"), of anti-tumour effects

and the prevention of carcinogenesis. The immuno-regulation exerted by the beta-glucans acts by linking glucan particles to the specific cellular-membrane receptors of this chemical compound. The activation of the transduction signal, going from the receptor of the membrane to the nucleus, is due to the metabolism of the macrophages. More precisely, the changes that the macrophages produce after their interaction with the beta-glucans impair the functional ability of the immune system, or its homeostasis.





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The mechanical response, when there is a cut, is thrombogenesis. The beta-glucans can deactivate the pathogenic mechanisms responsible for the occlusion of the blood vessels. The anticoagulant and antithrombic activities of the beta-glucans are similar to those of certain antithrombic agents such as heparin. Several scientific studies suggest that the macrophages are the key cells in the healing mechanism. The beta-glucans can activate the macrophages involved in the healing process. If the pharmacological properties of beta-glucans have been studied so much, it is because great hope has been placed in the exploitation of their immuno-regulating properties in severe pathologies such as HIV. It would appear in fact that beta-glucan interferes with the membrane of the red globules when they are infected by the HIV agent and thus prevent the spreading of the infection. To summarise "A cascade of interactions and reactions initiated by regulating the macrophages may also produce a conversion of the glucans, which results in an arsenal of defence".

Joyce K. Czop Ph.D., Dept. of Rheumatology and Immunology, Harvard Medical School

"This study definitely shows that the glucans (Beta1,3) have an action not only on the macrophages, but also on B lymphocytes and on the elimination of T cells".

P. Mansell, M.D., McGill University Cancer Research Unit, Victoria Hospital, Montreal, Canada





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Proved biological action

DRIELINE: The solution for keeping a young skin

DRIELINE

Natural product

Highly purified by biotechnological process

A battery of tests has demonstrated its biological effectiveness

For optimum action in combating ageing of the skin





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Double anti-ageing action 1° Preventive action: daily care of "intermediate skin"

Because of modern lifestyle and new habits, the skin needs to be protected sooner from cutaneous ageing.

Cosmetologists have shown that from twenty years of age, preventive care of the skin can delay ageing. It has been demonstrated that the use of cosmetics contributes greatly to maintaining the beauty and health of the intermediate skin of women aged between twenty and fifty.

To help the "intermediate skin" to stay young, DRIELINE exercises a preventive action by:

Reviving the skin's immune system and strengthening the skin's natural defences

Protecting the skin's sentry cells against the harmful effects of UVB

2° Repairing action: daily care of mature skin

Cutaneous ageing, though physiologically inevitable, is amplified by the environmental conditions. In fact, insufficiently protected and subjected to various external aggressions, the skin ages prematurely.

Generally from fifty years of age, we see a slowdown in the renewal of the epidermis resulting in harm to the cutaneous barrier. The skin becomes fragile and more sensitive to the harmful effects of the environment, which accentuates ageing even further.

DRIELINE regenerates "mature skin" in depth and helps it to regain its beauty by eliminating the ravages of time. It exercises a repairing and regenerative action thanks to the:

Anti-inflammation action

Activation of collagen synthesis

Through its action on the key cells of the skin's physiological balance, DRIELINE effectively combats the ageing factors.

Thus protected, preventively and permanently, the skin stays younger for longer.





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The ageing of the skin

The skin is the organism's shield and it is more than just an envelope covering the body. Above all, it is an organ of protection against the external environment.

As well as having this protective role, the skin is a reflection of the general health of the body. Because it is socially visible, its appearance and beauty has a particular importance in our contemporary society. This is demonstrated by the present trend for preventive and protective cosmetics, aimed at guarding the skin from ageing.

Now, cutaneous senescence depends on several factors, among which the external environment occupies a major place.

In fact throughout life the skin is subjected to a wide variety of external aggression (pollution, ultraviolet rays, prolonged exposure to the sun, etc.) and internal aggression (stress, etc.), which weaken the skin and accelerate the ageing process.

Faced with the amplification of these attackers related to modern living conditions (oxidizing stress, pollution), the body's defences are fighting a losing battle… the mechanisms of protection and repair of the tegument are no longer capable of fulfilling their role. The skin then ages prematurely and loses its beauty!

1° At a cellular level

The keratinocytes are today acknowledged, in the same way as the Langerhans cells, as essential and fundamental players in the cutaneous defence system.

They represent the majority of the cells in the epidermis and are engaged in an extremely precise programme of differentiation and maturation, subjected to the numerous interactions between the epidermal and dermal compartments. This process results in the construction of complex keratins and lipids, which protect the epidermis and its "barrier" component, the keratinous layer. This is the traditional and well-known protective mechanical role of the keratinocytes.

Even more interesting is the involvement of these cells in the cutaneous immune defence process. The keratinocytes are capable of reacting to a great variety of stimuli and of synthesising the mediators of cell communication (cytokines), which act on other cells, thus initiating an "immune cascade" of defence.

As for the Langerhans cells, also called the "sentries of the epidermis", they are the special macrophages of the skin, meaning the cells that rid the body of intruders (bacteria, remnants, toxins).

The dendrites that they transmit to the surface of the epidermis put them in contact with the exterior environment. They can then assume their role of supervision and unleash the cutaneous "alarm systems" during aggression by an exogenous element.

They are first in the line of fire for damage during the skin's exposure to ultraviolet rays.

"Solar rays damage the Langerhans cells by reducing their ability to produce cytokines in response to stimuli and by destroying them in cases of prolonged exposure. Now, the Langerhans cells play a determining role in "the





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immunological orchestra". They are perhaps even the conductor of the orchestra. An organism's ability to protect itself is therefore reduced" (Mansell P.W.A. 1994).

2° Direct consequences

To the number of changes related to cutaneous ageing, we find a big increase in the skin's fragility and the loss of its physiological balance:

Functional changes cause a decrease in the inflammation response ability and increased irritation of the skin, then producing feelings of discomfort

A drastic decrease in cell renewal (cell "turnover"), which may extend from 28 days to 60 days) A decrease in the metabolic activity of cutaneous cells, which cause a slowdown in collagen

synthesis, causing a slackening of the cutaneous tissue, among other things

To summarise, the integrity of the cutaneous barrier system is harmed, the skin's physiological balance is no longer sure.





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Effectiveness: the active anti-ageing cosmetic

DRIELINE a twofold cutaneous action

Thanks to its twofold action: prevention and repair, in cooperation with the metabolism of the organism, DRIELINE contributes actively to maintaining the integrity of the cutaneous barrier system.

DRIELINE

Its preventive action helps "intermediate skin" to stay young

Its repairing action stimulates mature skin and helps it to regain its beauty by eliminating the ravages of time

Revival and stimulation of the cutaneous Immune defence system

Through tests, DRIELINE demonstrates its power to:

♦ Stimulate the keratinocytes to produce interleukin-1 (IL-1)

♦ Regulate the immune system by the specific induction of the mediator cells (IL-1, IL-6 and IL-10)

♦ Improve the anti-microbe action of the keratinocytes, thus reviving the skin's defence system





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DRIELINE® stimulates the production of IL-1

Study of the production of IL-1 by human keratinocytes in culture. Equipment and method The first day, human keratinocytes are put in culture on plates of 24 wells with 2x104 cells per well. The second day, the culture medium is changed for a medium containing DRIELINE® at different concentrations. The third day, the production of cytokines is stimulated by the addition of stimulating agents (LPS and TNF-α t 10 µg/ml in each well). The fifth day, the supernatant of the cultures is recovered and measured out in IL-1 by the ELISA method. Results

DRIELINE® stimulates the response of the keratinocytes, which increases the production of chemical mediators such as IL-1, thus encouraging intercellular communication.

There is a significant increase in the

concentration of IL-1 in the culture receiving the dose

of 5% of DRIELINE®.

Production of IL-1 by the keratinocytes

20

30

40

50

60

Control

Sorbeol

0.25%

0.50%

1.00%

2.50%

5.00%

DRIELINE Concentration

IL-1

in p

g/m

L

+25 %





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Increased synthesis of RNA in the genomic research

This genomic research demonstrates in vivo the response of the keranocytes to the stimuli induced by the local application of DRIELINE®. Thus, the gene expression coding for the mediator cells in the cutaneous immune reaction has been quantified.

The research was led by Dr. ENK, of the department of dermatology at the Hadassah Medical Centre (Israel).

Equipment and method The test is performed on healthy volunteers of photo-types I or II, with cosmetic creams containing DRIELINE® as the sole active ingredient. The products to be tested are a placebo cream and three creams activated with 1%, 3% and 10% of DRIELINE®.

The products are applied in the quantity of 2 mg/cm2 on an area of 9 cm2 of the forearm of the volunteers, an area not

exposed to the sun. The forearm treated is left in the open air for 15 minutes, after which the surplus of cream is delicately removed with a clean cloth. The products to be tested are applied daily for 2 weeks. The first application is done by the investigator, who gives the volunteer oral and written instructions on how to apply the products. The last application (at the end of 2 weeks) is done by the volunteer, under the supervision of the investigator.

Sampling – analyses: 15 minutes after the last application, "suction blisters" are introduced into the test area, and the corresponding epidermis above these blisters is removed surgically. Blisters are also introduced into an untreated area of the forearm, by way of control. The fragments of epidermis are treated and then analysed by RT-PCR. Results

Expression of Interleukin-10, 1α, 6 (IL-10, IL-1α and IL-6) and of the "housekeeping gene" G3PDH by the keratinocytes following the local application of cosmetic containing DRIELINE®.

Expression of Interleukin-10 (IL-10) by the keratinocytes following the local application of creams containing DRIELINE

®.

Exp. N° 532/137 534/147 536/160 537/165

Control area 10* 886 1003 3758

Cream at 10% 961 1534 2626 8928

Cream at 3% ND 980 ND 9426

Cream at 1% ND 1251 ND 5804

Placebo cream ND 549 ND 958

* Densitometric units ND: Not Determined (absence of results due to insufficient formation of "blisters", RNA extracted is of poor quality or from an incomplete protocol)





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In the 4 experiments, the local application of creams containing DRIELINE® causes a significant increase in the transcription of IL-10 by the keratinocytes. On the other hand, the application of the placebo cream does not induce the expression of IL-10.

Expression of interleukin-1α (IL-1α) by the keratinocytes following the local application of creams containing DRIELINE®.

Exp. N° 532/140 534/147 536/160

Control area 1146 493 495

Cream at 10% 2016 1210 13528

Cream at 3% ND 1183 ND


Placebo cream ND 607 ND

The local application of creams containing 10% and 3% of DRIELINE® causes a significant increase in the transcription of IL-1α by the keratinocytes. Expression of Interleukin-6 (IL-6) by the keratinocytes following the local application of cream containing DRIELINE®.

Exp. N° 534/147 536/161

Control area 1499 495

Cream at 10% 3814 1049

Cream at 3% 3324 ND

Cream at 1% 1514 ND

Placebo cream 1150 ND

In the 2 experiments, the local application of creams containing 10% and 3% of DRIELINE®, leads to a significant increase in the transcription of IL-6, whereas the application of the placebo does not induce the expression of this cytokine.





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Expression of the "housekeeping gene" G3PDH by the keratinocytes following the local application of cream containing DRIELINE®.

Exp. N° 532/136 534/143 536/144

Control area 1120 596 7115

Cream at 10% 900 345 2353



Placebo cream ND 770 ND

The housekeeping gene G3PDH is representative of an overall metabolic activation. The fact that the application of creams containing DRIELINE® does not stimulate the expression of the "housekeeping gene" proves that DRIELINE® acts specifically. It is not the keratinocyte on its own that is stimulated, excessively producing everything that it is capable of synthesising and excreting. On the contrary, DRIELINE® regulates the immune system, specifically inducing the expression of IL-1α, IL-10 and IL-6.

DRIELINE®, formulated in a cosmetic cream applied on the skin, regulates the cutaneous immune defence system, specifically inducing the production of cytokines by the keratinocytes. DRIELINE® exercises a "biologically targeted" action, in vivo, in people.





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Stimulation of the anti-microbial action of the keratinocytes

Human keratinocytes have natural anti-microbial properties. The objective is to show the potentiator effect of DRIELINE® on the cytotoxicity of these cells with regard to micro-organisms.

Equipment and method

Freshly isolated human keratinocytes are put in culture, then a suspension of Candida albicans is added. The measure of cytotoxicity against Candida albicans was performed with the incorporation of different concentrations of DRIELINE® in the culture wells.

Results

The addition of DRIELINE® (up to 2.5%) in the culture medium improves the cytotoxicity of keratinocytes with regard to micro-organisms.

DRIELINE® amplifies the anti-microbial action of keratinocytes and helps the cutaneous system to defend itself. DRIELINE® maintains the balance of the cutaneous flora against micro-organisms.





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Protection of Langerhans cells against the harmful effects of UVB

A study of a skin explant shows that DRIELINE® protects the Langerhans cells against the harmful effects of UV, thus ensuring the integrity of the epidermis and its barrier function.

Previous studies have demonstrated that the local application of DRIELINE® regulates the cutaneous immune defence system.

The Langerhans cells are the leading cells in the skin's immune system. We have therefore studied the protection given by a solution of DRIELINE® on these cells in human skin explants subjected to UVB irradiation.

Equipment and Method

Skin explants of 8 mm diameter are sampled during abdominal plastic surgery on a woman aged twenty-six. The explants are put in culture on plates with 24 wells, containing 300 µl of medium per well, epidermal surface upwards.

Product to be tested: DRIELINE, diluted to 0.5% and 5% in an aqueous solution of NaCl at 0.9%.

Positive reference: Protective mixture consisting of vitamin C and glutathione reduced in aqueous solution.

Products are applied on the surface of the epidermises to be treated. The application is repeated at time T24h and T48h. At time T72h, skin explants are irradiated with UVB irradiation (total irradiation of 1.5 J/cm²).

Langerhans cells are marked and observed: At time T96h, the skin explants are frozen and cross-section slices are made. These are treated with the antibody anti-CD1a, a specific Langerhans cells marker. The slices are then observed by epifluorescent microscope, and the fluorescent Langerhans cells are counted (count of 6 fields per slide, which is 12 measurements per treatment).

Anti-CD1a marking colouring of the nuclei





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Results The percentage of protection of the applied product is calculated according to the viability of Langerhans cells. The negative reference (no UVB irradiation) equals total protection and the positive reference (UVB irradiation) equals no protection.

Product Concentration Average number of cells

Percentage of protection

– UVB Control 0 57 100

+ UVB

Control 0 26 0

Ref. ⊕ 100 µg/ml 42 51

DRIELINE® 0.5% 44 59

Control not irradiated (objective 10).

UVB irradiation of human sk in explants. Langerhans cells are marked by the anti-CD1a antibody.





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Control irradiated (objective 10). Positive reference (objective 10).

UVB irradiation of human sk in explants. Langerhans cells are marked by the anti-CD1a

antibody.

UVB irradiation of human sk in explants after treatment by the reference compound.

Langerhans cells are marked by the anti-CD1a antibody.

DRIELINE® at 5% (objective 10). DRIELINE® at 0.5% (objective 10).

UVB irradiation of human sk in explants after treatment by DRIELINE® 5%. Langerhans cells

are marked by the anti-CD1a antibody.

UVB irradiation of human sk in explants after treatment by DRIELINE® 0.5%. Langerhans cells

are marked by the anti-CD1a antibody





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This demonstration, performed in an experimental model very close to the "in vivo" experiment, is not sufficient for a conclusion regarding the mechanism involved in the protective phenomenon observed. However, all the information acquired in the laboratory and in vivo allows us to imagine a Langerhans cell protective mechanism that is both direct and indirect.

DRIELINE provides

Direct anti-radiation protection (Langerhans cells are extremely sensitive to aggression from the free radicals induced by UV rays).

Indirect protection: improved defence and protection mechanisms for the cells, thanks to DRIELINE stimulation of cell communication in skin explants.

This study, performed on human skin explants, reveals the very good protective effect of DRIELINE: 59% protection with a concentration of only 0.5%.





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Clinical Anti-inflammation action of DRIELINE®

In tests performed in vivo on the reduction of erythema and induced irritation, DRIELINE is extremely effective. It has been proved that the use of this active ingredient in local applications is a great help in restoring the physiological balance of the skin.

This property has been evaluated on volunteers, simultaneously with a medical reference, in order to underline the significant effectiveness of DRIELINE.

Equipment and method:

Erythema is induced by stripping on healthy volunteers. Volunteers are then treated with 2% DRIELINE or with an anti-inflammation reference product, hydrocortisone. All the results are compared with those of an untreated control. The treatment is applied twice a day for five days.

The intensity of the erythema is evaluated by laser Doppler velocimeter.

Results:

At 2% DRIELINE has an anti-inflammation action identical to that of a product containing 0.1% of hydrocortisone, a medicinal reference.

DRIELINE® has demonstrated its potent anti-inflammatory properties as we observed a significant reduction of the erythema in a time dependant manner.





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By activating the synthesis of collagen, DRIELINE acts as a real in-depth tissue builder, "re-fleshing" the skin from inside and even acting on healing.

Cytokines

Lesions

Cell activation. Secretion of growth

factors

Neovascularisation and cell proliferation.

Re-epithelialisation. Destruction of debris from cells and micro-organisms

Cell migration

Plate aggregation Degranulation Haemostasis

Haemorrhage. Formation of the complement.

3 d a y s

Granulation Formation of new tissue

Healing. Formation of the extracellular matrix.

Remodelling of the tissue.

Complete cicatrisation

Diagramatic representation of the healing process.

1

m o n t h

12 d a y s





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Collagen is the component that supports the dermal tissue, and is partly responsible for the skin's firmness. A reduction in its synthesis causes the skin to become thinner and encourages the appearance of wrinkles and lines.

The following test is performed to show the induction of collagen synthesis by DRIELINE.

Equipment and method:

Radio marked proline is added to a culture of human fibroblasts. Proline is an amino acid constituent of collagen, therefore the marked molecules are revealed in the collagen newly synthesised by the fibroblasts. DRIELINE is incorporated in different concentrations in the culture wells in comparison with the control.

Results:

In the different concentrations tested, DRIELINE stimulates the synthesis of collagen by the fibroblasts.

DRIELINE, used at low concentrations stimulates collagen synthesis by 50%.





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Clinical Efficacy





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Stimulation of healing

With the strength of the evidence revealed regarding the action of DRIELINE on the secretion of various cytokines, particularly of IL-1, IL-6 and on the synthesis of collagen, we evaluated under medical control its healing effectiveness and its tolerance as model for "tissue remodelling".

Equipment and Method

This multicentered study was performed on 22 volunteers presenting crevices in the feet, on which a cream containing DRIELINE (at 10%) as the only active ingredient was applied twice a day for 28 days.

Criteria for inclusion: the subjects had to satisfy all the following criteria for inclusion:

• Man or woman

• Presenting significant crevices on the feet

• Undertaking not to use any other cosmetic or medicinal product in local application on the feet for the duration of the study

• Capable of following the indications ensuing from the protocol and, in particular, of answering the self-evaluation questionnaire.

Criteria for exclusion: the subjects must have none of the following: ulcerated crevices, diabetes, significant circulatory problems in areas where the product is to be applied, underlying neuropathy, medical treatment likely to influence the quality of healing, pregnancy.

Application method: the product must be applied every day, morning and evening for 28 days, on a clean, dry foot. The product is applied for 28 days, even if the crevices are completely healed before the end of the study. The hygiene habits regarding the area where the product is applied must not be changed for the duration of the study. No other healing or antiseptic product is allowed on the area where the product is applied, and there must be no exposure to the sun or U.V. sessions. Any interruption in the application of the product during the study must be reported in the comments notebook as well as the reasons for this interruption.

Procedure of the examinations: the study lasts for 28 days. The investigator must carry out an inclusion examination (Day 0) and an end-of-study examination (Day 28). A questionnaire evaluating the product and its use must be completed by the volunteer the day before the end-of-study examination.





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Description of the crevices

Criteria Characteristics Percentage of subjects included

Age of the crevices Several years From 1 month to two years Less than 1 month

45.5% 18% 36.5%

Location of the crevices

Heel Outside of the foot Top of the foot Outside, toes, sole Both feet

77% 27% 14% 14% 14%

Number of crevices Numerous crevices Average number per subject

35% 3

Size of the crevices Average size 1.31 cm or 0.71 cm²

Appearance of the crevices

Dry crevices Open crevices Deep crevices Bleeding crevices Superficial crevices Hyperkeratosis

38% 24% 24% 14% 19% 24%

Results

Evaluation of effectiveness by the investigator

Evaluation of effectiveness by the volunteers

Evaluation of tolerance

Photographs





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Evaluation of effectiveness by the investigator

Evaluation of healing by the investigator

On Day 28, the investigator noted complete healing or almost complete of crevices among 77% of subjects.

It has to be stated that on the 4 people where the investigator noted an absence healing, one presented on Day 0 numerous very long crevices (5 cm) associated with severe hyperkeratosis, and another suffered from bleeding crevices. Finally, a third person had not respected the protocol, applying the product once a day and stopping the treatment after 3 weeks.

Evolution of the functional discomfort

After treatment, a decrease in functional discomfort was noted among 82% of subjects.

Functional discomfort - Subject 22

0

10

20

30

40

50

60

70

80

Absent Low Average Serious

%

Before treatment

After treatment

Evaluation of the pain related to the crevices

After treatment, a decrease in the pain related to the crevices was noted among 95% of subjects.

Pain - Subjects = 22

0102030405060708090

Absent Low Average Serious

Before treatmentAfter treatment





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Evaluation of the skin's toughness on the feet

After treatment, the investigator noted increased skin toughness among 64% of subjects.

Strength of the skin - Subjects = 22

0

10

20

30

40

50

60

Very low Low Average Serious

Before treatment

After treatment

Evaluation of the skin's softness on the feet

After treatment, the investigator noted an improvement of the skin's softness among 64% of subjects.

Softness of the skin - Subjects = 22

0

10

20

30

40

50

Very low Low Average Serious

Before treatmentAfter treatment

Overall evaluation of effectiveness

The investigator considered the product effective among 82% of subjects in the study.

Subjects = 22

0

10

20

30

40

Noteffective

Fairlyeffective

Effective Veryeffective





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Evaluation of effectiveness by the volunteers

Time for complete healing of crevices

The average time for complete healing of crevices is 14 days.

Time for complete disappearance of functional discomfort

The average time for complete disappearance of functional discomfort is 11 days.

Time for complete disappearance of pain related to the crevices

complete disappearance of pain related to the crevices is 10 days

Evaluation of the skin's toughness on the feet

On Day 28, 77% of subjects noted increased toughness of their skin.

Subjects = 15

0102030

405060

1stweek

2ndweek

3rdweek

4thweek

Subjects = 17

0

10

20

30

40

50

1st week 2nd week 3rd week 4th week

Subjects = 10

0

20

40

60

80

1st week 2nd week 3rd week 4th week

Subjects =22

0

10

20

30

40

50

None Low Average High





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Evaluation of the effectiveness of the product

82% of subjects considered the product effective.

Self- Evaluation / Perception of the volunteers

Preference for the product tested versus the usual product

92% of subjects prefer the product tested to their usual product.

Subjects =22

0

10

20

30

40

50

Noteffective

Fairlyeffective

Effective Veryeffective

Subjects =12

0

20

40

60

80

100

Usual product Product w ith Drieline





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Photographic record

For better visualisation of the pathology of patients suffering from crevices, and to provide a record of the repairing action of cream containing DRIELINE, the same study was repeated to obtain a photographic record. The study was conducted on three patients suffering from fairly pronounced lesions on the feet. Day 1 was the inclusion examination and Day 28 was the investigator's evaluation.

Patient 1

Day 0: crevices for two years, more than 5 crevices per foot, dry crevices, a lot of functional discomfort, a lot of pain.

Day 28: Investigator's evaluation: almost complete healing; crevices not very deep; in process of healing.

Functional discomfort: absent, (disappearance of the discomfort: 2 weeks).

Pain: absent (disappearance of the pain: 1 week).

Product considered effective, tolerance considered very good.

Patient 1 – Day 0

Patient 1 – Day 28

Patient 1 – Day 0






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Patient 2

Day 0: Crevices for several years, very dry crevices, average functional discomfort, much pain.

Day 28: Investigator's evaluation, complete healing, functional discomfort absent, pain absent, product considered very effective.

Patient 2 – Day 0


Patient 2 – Day 0






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Patient 3

Day 0: Crevices for several years from 2 to 3 cm long, dry crevices, much functional discomfort, much pain.

Day 28: Investigator's evaluation: complete healing, functional discomfort absent, pain absent, product considered effective.

Patient 3 – Day 0


Used at a concentration of 10% with daily local application, DRIELINE accelerates the healing of crevices with a very good product tolerance. This remarkable action of DRIELINE makes it an excellent cosmetic active ingredient for not only restoring and regenerating the epidermis from the outside but also from inside by acting directly on the collagen system.





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New consumer test on stretch marks

Erase It Concept contains 3 active ingredients that will specifically help minimize the appearance of existing stretch marks and improve the overall evenness and firmness of the skin. Test protocol: 65 women, 18 to 45 years old, with pink or purplish stretch marks on thighs, hips, buttocks, stomach and/or breast. Applied the anti-stretch mark cream with 1.5% Drieline, 1.5% ChroNOline & 1.5% Exo-T, twice daily during 8 weeks. Answered questionnaires after 4 and 8 weeks.

Consumers agree, the skin is more toned and stretch marks are less visible for a more attractive look!





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DRIELINE, how to use it





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Cosmetic use

Anti-ageing care Protective care

Repairing and restructuring care Dermo-cosmetic care

Recommendation of use

DRIELINE is an easy-to-use natural ingredient. It can be formulated in emulsions (cream, milk, fluid, serums), gels, lotions, etc.

DRIELINE is compatible with the other ingredients used in formulations and is stable in the final cosmetic product.

Shake before use. Incorporate at the end of the formulation at a temperature less than 60°C.

Utilisation concentration: 0.5-2%





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Indicative formula

Anti-ageing cream for mature skin

PHASE TRADE NAME % P/ P A1 Emulium Delta 4.50 A2 Amerchol L101 5.70 A3 Amerlate W 2.00 A4 Vegetable oil of Calendula 2.00 A5 LNST 98 2.00 B1 Demineralized water QSP 100 B2 Carbopol ultrez 10 (2% solution) 10.00 C Abill B8839 6.00 D1 Demineralized water 5.00 D2 TEA 0.20 E1 Phenonip 0.50 E2 Natural glycerin 4.00 F Fluidamid DF 12S 4.00 G DRIELINE 2.00 H Fragrance C3680/2 0.30

Procedure A4-5→ A 1-3 75 °C A 75°C → B 75 °C C → AB 70 ° C D → ABC 65 °C E → ABCD 60 °C F → ABCDE 55 °C G → ABCDEF 45 °C H → ABCDEFG 35 °C

Stability 1 month at 50°C

1 month at 4°C 1 month in the light

pH 6

Viscosity Brookfield RVT m6, vit. 2.5: 216 000 cps



Lucas Meyer Cosmetics Place de la Cité, Tour de la Cité, 2600 boul. Laurier, #900, Québec (Québec) G1V 4W2 Canada www.lucasmeyercosmetics.com - 38 -

http://www.unipex.com/



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