ADIPOSLIM: “top model” shape adipocytes to correct ... · This fat storage reduction is reinforced by the inhibition of the Lipoprotein Lipase (-22% at 0.1%am). Protocol: measurement

SOS SILHOUETTE PROGRAM

ADIPOSLIM: “top model” shape adipocytes to correct cellulite!

ADIPOLESS: less adipocytes to maintain your “silhouette”!

SEPPIC PATENTS

3364/GB/01/ JULY 2006 - 2

SOS SILHOUETTE PROGRAM –ADIPOSLIM & ADIPOLESS A WINNING DUO

ADIPOSLIM ADIPOLESS

INHIBITS and ELIMINATES FAT STORAGE to get rid of existing cellulite!

“SILHOUETTE” MAINTENANCE to prevent

new fat forming!

A WINNING SLIMMING DUO

CURATIVE action: for “top model”

shape adipocytes!

PREVENTIVE action: less functional adipocytes!

3364/GB/01/ JULY 2006 - 3


Food Triglycerides (TG)

Free fatty acids (FFA)

Pre-Adipocytes (no storage of fats)Adipocytes

+60% volume

ADIPOLESS:PREVENTS THE

RECRUITMENT OF NEW ADIPOCYTES

via AN ANTI-ADIPOGENESIS

ACTION

(anti-angiogenesis + anti-maturation).

ADIPOSLIM:INHIBITS and ELIMINATES fat storage

Recruitment and Maturation

Storage of fat (TG)

Lipogenesis (fat storage)

INNOVATIVE

ACTION

ADIPOSLIM

ADIPOSLIM

ADIPOLESS

MMP9 signals

( nutrientS, ADIPOGENESIS)

ADIPOLESS

Blood vessels

+ Blood vessels

Blood vessels

Angiogenesis = neovascularization

ADIPOSLIM: “top model” shape adipocytes to correct existing cellulite.

SEPPIC patent


3364/GB/01/ JULY 2006 - 5

ADIPOSLIM - STRUCTURE

Lauric acid (C12) Proline

derived from plants derived from biotechnology

(lipophilic) (hydrophilic)

Lauroyl proline

INCI name: Sorbitan laurate and Lauroyl Proline

Amphiphilic structure=> Excellent cutaneous bio-affinity

Defined, titrated and stable ingredient (liquid form)

3364/GB/01/ JULY 2006 - 6

ADIPOSLIM: TOP MODEL SHAPE ADIPOCYTES VIA A FAT STORAGE INHIBITION AND ELIMINATION !

ADIPOSLIMADIPOSLIM

=> “Decoy” function + LPL inhibition

⇒ cAMP increase via a PDE-3 inhibition and an adrenergic receptors regulation

Activates lipolysis

Recycles fat

Inhibits the entry of FFA

into adipocytes

2. ELIMINATION of 2. ELIMINATION of FAT STORAGEFAT STORAGE

A slimming treatment for A slimming treatment for adipocytesadipocytes ……

1. INHIBITION of FAT 1. INHIBITION of FAT STORAGE STORAGE

AdipocytesAdipocytes on aon adiet …diet …

3.3. CELLULITE CELLULITE CORRECTOR CORRECTOR

Eliminates existing Eliminates existing fat!fat!

Clinically Clinically demonstrateddemonstrated

⇒ Fats is “burned” and recycled into cellular energy (ATP)

ADIPOSLIM:ADIPOSLIM:

1.1. INHIBITION OF FAT STORAGEINHIBITION OF FAT STORAGE

AdipocytesAdipocytes on a diet!on a diet!

3364/GB/01/ JULY 2006 - 8

ADIPOSLIM: ADIPOCYTES ON A DIET VIA A “FAT STORAGE” INHIBITION !

Triglycerides

FFALIP

OG

EN

ESIS

Lipoprotein lipase (LPL)ADIPOSLIM -

+ Glycerol

Gycerol +

ADIPOSLIM + Lipase

Adipocyte

Adenylate cyclase

5'-AMP

cAMP

α2 receptor(anti-lipolytic)

β receptor(lipolytic)

+

_

Phosphodiesterase 3 (PDE3)ADIPOSLIM -

Activates Activates ELIMINATION ELIMINATION

of of FAT STORAGEFAT STORAGE

-

+

ATP

FFA

mitochondria

ADIPOSLIM +

FOOD

TG

ADIPOSLIM -

LIPOLYSIS

Inhibits Inhibits FAT FAT

STORAGESTORAGE

(diet)(diet)

FAA entry

FFA OXIDATION => ATP

+

FFA

EXIT (removal)

Glucose

FFA

ADIPOSLIM +

+ ADIPOSLIM

ADIPOSLIM +

ADIPOSLIM -

3364/GB/01/ JULY 2006 - 9

ADIPOSLIM: ADIPOCYTES ON A DIET VIA A “FAT STORAGE” INHIBITION !

ADIPOSLIM inhibits the entry of FFA into mature adipocytes, thus putting them on a diet !

This fat storage reduction is reinforced by the inhibition of the Lipoprotein Lipase (-22% at 0.1%am).

Protocol: measurement of a non-metabolizable fluorescent fatty acid entry (5 methyl-BDY-dodecanoic acid) into mature adipocytes (3T3) with or without ADIPOSLIM (positive control = insulin and negative control = cold)

05000

10000150002000025000300003500040000

Entry offatty acids

(fluorescence unit/mg

of proteins)

Control Cold Insulin150 nM

0.0125 0.025

ADIPOSLIM (% am)

*

*

*

*

*: p<0.05

1. INHIBITS THE ENTRY OF FFA INTO ADIPOCYTES:

- 90%

- 47%

+37%

-64%

% relative to control

am: active matter


2. Activates ELIMINATION of 2. Activates ELIMINATION of FAT STORAGEFAT STORAGE

forfor “top model” shape “top model” shape adipocytesadipocytes !!

3364/GB/01/ JULY 2006 - 11

ADIPOSLIM: “TOP MODEL” SHAPE ADIPOCYTES VIA AN ELIMINATION OF FAT STORAGE !

Triglycerides

FFALIP

OG

EN

ESIS


+ Glycerol

Gycerol +

ADIPOSLIM + Lipase

Adipocyte

Adenylate cyclase

5'-AMP

cAMP



+

_

Phosphodiesterase 3 (PDE3)

ADIPOSLIM -

Activates Activates ELIMINATIONELIMINATION

of FAT of FAT STORAGESTORAGE

-

+

ATP

FFA

mitochondria

ADIPOSLIM +

FOOD

TG

ADIPOSLIM -

LIPOLYSIS


STORAGESTORAGE

((dietdiet))

FAA entry


+

FFA

EXIT (removal)

Glucose

FFA

ADIPOSLIM +

+ ADIPOSLIM

ADIPOSLIM +

ADIPOSLIM -

3364/GB/01/ JULY 2006 - 12

ADIPOSLIM: “TOP MODEL” SHAPE ADIPOCYTES VIA AN ELIMINATION OF FAT STORAGE !

ADIPOSLIM efficiently “eliminates” fats (FFA) from male or female adipocytes => “Caffeine-like” lipolytic activity

2.1 ACTIVATES LIPOLYSIS (= FAT REMOVAL) IN THE ADIPOCYTES

0

100

200

300

400

Lipo

lytic

act

ivity

: %re

lativ

e to

con

trol

0

200

400

600

800

Lip

oly

tic

acti

vity

:%

rel

ativ

e to

co

ntr

ol

FEMALE ADIPOCYTES (13 donors) MALE ADIPOCYTES (1 donor)

0.01% am Caffeine

0.01% am Caffeine

0.0025 % am ADIPOSLIM

0.0025% am ADIPOSLIM

+ 392% + 385% + 719%+ 674 %

Protocol: measurement of triglycerides lipolysis by assay of free fatty acids (FFA) expelled of normal human adipocytes (obtained from male and female abdominal cosmetic surgery) with or without ADIPOSLIM (Positive control = CAFFEINE)

am: active matter

* * **

* P < 0.05

3364/GB/01/ JULY 2006 - 13

ADIPOSLIM: LIPOLYSIS VIA THE cAMP PATHWAY

Triglycerides

FFALIP

OG

EN

ESIS


+ Glycerol

Gycerol +

ADIPOSLIM + Lipase

Adipocyte

Adenylate cyclase

5'-AMP

cAMP



+

_




-

+

ATP

FFA

mitochondria

ADIPOSLIM +

FOOD

TG

ADIPOSLIM -

LIPOLYSIS


STORAGESTORAGE

((dietdiet))

FAA entry


+

FFA

EXIT (removal)

Glucose

FFA

ADIPOSLIM +

+ ADIPOSLIM

ADIPOSLIM +

ADIPOSLIM -

3364/GB/01/ JULY 2006 - 14


ADIPOSLIM increases cAMP level, a KEY substance in the elimination of fat (more effective than caffeine):

How ?

⇒Via a PDE3 inhibition (-96% at 0.025% am ADIPOSLIM ) => cAMP accumulation

⇒Via an adrenergic receptor regulation (stops inhibition of lipolysis induced by an α adrenergic agonist or by a ß adrenergic antagonist) = cAMP accumulation = ACTIVATION OF LIPOLYSIS

2.1.1. Lipolysis activation via an increase in a key substance = cAMP

Protocol: measurement of cAMPlevels in normal humanadipocytes (8 donors)

0

100

200

incr

ease

in c

AM

P

leve

l in

% r

elat

ive

to c

on

tro

l

0.01% am Caffeine 0.0025% am ADIPOSLIM

+ 86 %

+ 201%

* P < 0.05*

*

am: active matter

3364/GB/01/ JULY 2006 - 15


ADIPOSLIM inhibits PDE3, thus inducing the intracellular cAMP accumulation in the adipocytes (“caffeine-like” inhibition of PDE3) => EXPULSION of FFAs.

Protocol: measurement of PDE3 in vitro activity with a radioactive cAMP.

-100

0

% in

hib

itio

n o

f P

DE

3 re

lati

ve t

o

con

tro

l

0.1% am Caffeine 0.025% am ADIPOSLIM

* P < 0.05

* *

2.1.1.1. cAMP via Inhibition of PDE 3: (phosphodiesterase 3):

-100 % -96 %

2.1.1. Lipolysis activation via an increase in a key substance = cAMP

am: active matter

3364/GB/01/ JULY 2006 - 16


2.1.1.2. cAMP via regulation of adrenergic receptors:

0

10

20

30

40

50

60

70

LIPO

LYSI

S (N

EFA

µg/

ml)

Control BRIMONIDINE10-6 M

PHENTOLAMINE (10-5 M)

ADIPOSLIM (0.0025% am)

-85%

+ BRIMONIDINE 10-6 M

**

*

*: p<0.05 (relative to the Brimonidine group)

0

20

40

60

80

100

120

140

Control PROPRANOLOL(10-5 M)

ISOPROTERENOL(10-4 M)

ADIPOSLIM (0.0025% am)

-18%

LIPO

LYSI

S (N

EFA

µg/

ml) + PROPRANOLOL

10-5 M

*

*

*

*: p<0.05 (relative to the PROPRANOLOL group)

Alpha 2 receptor: Like phentolamine (alpha 2 antagonist), ADIPOSLIM totally stops the inhibition of lipolysisinduced by brimonidine (α 2 agonist) => ACTIVATION OF LIPOLYSIS

2.1.1. Lipolysis via an increase in a key substance = cAMP

Beta 2 receptor: Like lisoproterenol (beta 2 agonist), ADIPOSLIM totally stops the inhibition of lipolysis induced by propranolol (β 2 antagonist) => ACTIVATION OF LIPOLYSIS

am: active matter

3364/GB/01/ JULY 2006 - 17

ADIPOSLIM: RECYCLING of FFAs produced by LIPOLYSIS into ENERGY (ATP)

Triglycerides

FFALIP

OG

EN

ESIS


+ Glycerol

Gycerol +

ADIPOSLIM + Lipase

Adipocyte

Adenylate cyclase

5'-AMP

cAMP



+

_




-

+

ATP

FFA

mitochondria

ADIPOSLIM +

FOOD

TG

ADIPOSLIM -

LIPOLYSIS


STORAGESTORAGE

((dietdiet))

FAA entry


+

FFA

EXIT (removal)

Glucose

FFA

ADIPOSLIM +

+ ADIPOSLIM

ADIPOSLIM +

ADIPOSLIM -

3364/GB/01/ JULY 2006 - 18

ADIPOSLIM: MELTING OF ADIPOCYTES VIA AN ELIMINATION OF FAT STORAGE !

Fat is “burned” and recycled into available cellular energy ATP.

Therefore, FFAs are not stored as Triglycerides again.

Adipocytes are effectively “emptied” of all their fat.

2.2. RECYCLES FATS INTO ENERGY (= ATP)

5600

5800

6000

6200

% increase in intracellular

ATP relative to the control

Protocol: measurement of intra-adipocytIC ATP with or without ADIPOSLIM (incubation = 2 hours).

Done on normal human adipocytes.

+5794%

+6062%

0.25 ppm am ADIPOSLIM

25 ppm am ADIPOSLIM

*

*

=> Becoming of FFAs released by lipolysis ?

* P < 0.05

(= 0.000025%) (= 0.0025%)

am: active matter


3. Cellulite corrector3. Cellulite corrector

In vivo efficacyIn vivo efficacy

3364/GB/01/ JULY 2006 - 20

ADIPOSLIM: CELLULITE CORRECTOR

- Adiposlim at 3% as(formula 7028) vs placebo => cancelled massage effect

- 19 volunteers

- 1 month of treatment on the thighs

⇒ 1. Visual improvement of cellulite (dermatological scoring) + topological illustration (skin relief print )

⇒ 2. Measurement of anti-orange peel effect (reduction in fat infiltration).

Cream-gel tested No. 7028 (without caffeine)

3.1. CLINICAL TEST PROTOCOL:

• SEPINOV EMT10 (Hydroxyethyl acrylate & Sodiumacryloyldimethyl taurate copolymer – SEPPIC)

3.00 %

• Water / Aqua Qsp 100%• Glycerin 10.00 %• Isononyl isonanoate 4.00 %• Cyclopentasiloxane 2.00 %• Phenoxyethanol 0.35 %• Methyl paraben 0.15 %• Ethyl paraben 0.15 %• Ethanol 30.00%• Chlorphenesin 0.20 %• Fragrance 0.20 %• ADIPOISLIM (Sorbitan laurate and lauroyl Proline – SEPPIC) 3.00 %• NAOH (12% solution) Qs pH= 5.2

3364/GB/01/ JULY 2006 - 21


3.2. VISUAL IMPROVEMENT OF CELLULITE ON D30 :

-15-13-11-9-7-5-3-11

% visual reduction of

cellulite (D28 -D0

score)

=> Dermatological scoring:

Formula with 3% ADIPOSLIM (as) Placebo

Positive effect obtained for 71%

of volunteers

** P < 0.05

ADIPOSLIM significantly and visually corrects cellulite without any massage effect.

-12%

-6%

Before treatment (D0):

=> Thigh print:

After treatment (D28) of the formula with 3% Adiposlim: surface appearance is smoothed

cp: commercial product

3364/GB/01/ JULY 2006 - 22


3.3. REDUCTION OF ORANGE PEEL EFFECT

-15-13-11-9-7-5-3-11

% reduction of fat infiltration

(D28 -D0)

=> Ultrasound measurement of dermal density (= inversely proportional to fat infiltration)

Formula with 3% ADIPOSLIM (cp) Placebo

Positive effect obtained for 71% of

volunteers

*

* P < 0.05

ADIPOSLIM significantly limits dermal fat infiltration. It thus reduces the “orange peel” appearance of the skin.

-11%

-8%

cp: commercial product

3364/GB/01/ JULY 2006 - 23

ADIPOSLIM: “TOP MODEL” SHAPE ADIPOCYTES VIA A FAT STORAGE INHIBITION AND ELIMINATION !

ADIPOSLIMADIPOSLIM

=> “Decoy” function + LPL inhibition

Activates Lipolysis

Recycles fat

3.3. Eliminates existing Eliminates existing fat !fat !

Clinically demonstrated :Clinically demonstrated :Improvement in surface Improvement in surface

appearance appearance –– reduction in orange reduction in orange peel effectpeel effect

⇒ Fats is “burned” and transformed into cellular energy (ATP)

Adiposlim > Caffeine

⇒ Increase of cAMP via a PDE-3 inhibition and a regulation of adrenergic receptors

Inhibits the entry of FFAs

into adipocytes

2. ELIMINATION of 2. ELIMINATION of FAT STORAGEFAT STORAGE

A slimming treatment for A slimming treatment for adipocytesadipocytes ……

1. INHIBITION OF FAT 1. INHIBITION OF FAT STORAGE STORAGE

AdipocytesAdipocytes on aon adiet …diet …


4. Tolerance4. Tolerance

3364/GB/01/ JULY 2006 - 25

ADIPOSLIM - TOLERANCE

ADIPOSLIM has an excellent tolerance profile :

.Very well tolerated when topically applied

. Non-sensitizing

. Non-mutagenic

Recommended dose for total safety: up to 3% in topical cosmetic applications


5. Formulation guidelines5. Formulation guidelines

3364/GB/01/ JULY 2006 - 27

ADIPOSLIM can be incorporated up to ADIPOSLIM can be incorporated up to 3%3% in all types of in all types of topical formulas. It can be easily incorporated into slimming topical formulas. It can be easily incorporated into slimming projects:projects:

Yellow opalescent liquid Lipophilic

Color and odor stable over time.

Non sensitive to heat and shearing – Compatible with cold process.

Incorporation before emulsion (in the heated oily phase) or after emulsion, while still hot.

May generate electrolytes during neutralization => Use of SEPIPLUS range polymers recommended.

Compatible with caffeine, ethanol.

ADIPOSLIM: FORMULATION GUIDELINES

Suitable for White emulsions or cream-gels (with or without fragrance).

3364/GB/01/ JULY 2006 - 28

CELLULITE CORRECTION CARE – CAFFEINE FREE –PROVEN EFFICACY - 7028

Cream gel with ADIPOSLIM tested in vivo on 19 volunteers. Visual cellulite improvement obtained on 71% of volunteers after only one month of treatment.

Formula

A • SEPINOV EMT10 (Hydroxyethyl acrylate & Sodium acryloyldimethyl taurate copolymer – SEPPIC)

3.00 %

• Water Qsp 100% B • Glycerin 10.00 % C • Isononyl isonanoate 4.00 % • Cyclopentasiloxane 2.00 % • Phenoxyethanol 0.35 % • Methyl paraben 0.15 % • Ethyl paraben 0.15 %

D • Ethanol 30.00% • Chlorphenesin 0.20 % • Fragrance 0.20 %

E • ADIPOSLIM (Sorbitan laurate and Lauroyl Proline – SEPPIC) 3.00 % F • NAOH ( 12% solution) Qs pH= 5.2

3364/GB/01/ JULY 2006 - 29

INVISIBLE LIQUID SLIMMING AND FIRMING PATCH - 7025

Original formula for a second-skin treatment combining ADIPOSLIM with SEPILIFT DPHP (firming action) and SESAFLASH (rapid improvement in

surface appearance).

Formula

A • Polyvinyl Alcohol (20% solution in water) 40.00%• Water Qsp 100%• Ethanol 30.00%• Chlorphenesin 0.20%• SEPINOV EMT10 (Hydroxyethyl Acrylate / Sodium Acryloyl dimethyl taurate

copolymer - SEPPIC)1.00%

• Xanthan gum 0.20%B • SESAFLASH (Glycerin & Acrylates copolymer & VP/ Polyglycol ester &

Hydrolyzed Sesam Protein PG-propyl Methylsilanediol - SEPPIC)3.00%

C • ADIPOSLIM(Sorbitan Laurate & N-Lauroyl Proline- SEPPIC) 3.00%D • SEPILIFT DPHP (Dipalmitoyl Hydraoxyproline - SEPPIC) 1.00%

• Water 10.00%

3364/GB/01/ JULY 2006 - 30

INTENSE LIPO-STOP SLIMMING CARE 7026

Formula

ADIPOSLIMTM associated with CAFFEINE for a powerful lypolytic effect.

A • SIMULSOL 165 (Glyceryl stearate and PEG-100 stearate - SEPPIC) 2.00 % • MONTANOV 202TM (Arachidyl alcohol & behenyl alcohol & arachidyl

glucoside - SEPPIC) 3.00 %

• Caprilic Capric triglyceride 15.00 % B • SEPIPLUS 400 (Polyacrylate 13 /Polyisobutene /Polysorbate 20 – SEPPIC) 0.20 % C • Chlorphenesin 0.20 % • Methyl paraben 0.30 % • Ethyl paraben 0.20 % • Caffeine 5.00 % • Water Qs 100 %

D • Ethanol 20.00 % E • ADIPOSLIM (Sorbitan Laurate & Lauroyl Proline- SEPPIC) 3.00 % • Fragrance 0.07 %


6. Summary of key benefits6. Summary of key benefits

3364/GB/01/ JULY 2006 - 32

ADIPOSLIM KEY BENEFITS

1. Lipo-aminated structure for targeted adipocytes efficacy (vectorization of titrated Lauroylproline) – SEPPIC PATENT

2. Dual action for “TOP MODEL” SHAPE ADIPOCYTES !

⇒ 1. Inhibition of Fat Storage => puts adipocytes on a diet by inhibiting the entry of free fatty acids

⇒ 2. Elimination of Fat Storage => fat is expelled from the adipocytes and recycled into energy

3. Cellulite corrector without massage: efficacy clinically demonstrated after 1 month of treatment (versus placebo)

4. Excellent tolerance for cosmetic applications (3%)

5. Perfect cosmetic stability – can be used in cream-gels & emulsions – compatible with caffeine and ethanol.

6. The “Plus Points” in comparison with caffeine:=> INHIBITION of FAT STORAGE / Greater ELIMINATION of FAT

STORAGE (improved Lipolysis + recycling of FFA into energy) / Formulation advantages (stability & ease of use) / Regulatory issue

ADIPOLESS:

Less adipocytes to maintain your “silhouette”!Anti-Adipogenesis innovation.

SEPPIC and Biopharmacopea patent


3364/GB/01/ JULY 2006 - 34

ADIPOLESS - STRUCTURE

INCI name: Butylene Glycol and Chenopodium Quinoa Seed Extract

ADIPOLESS, a very high-quality plant extract with new powers

QUINOA from CANADA - Organic crop

conforming with international

standards

=> No herbicides, pesticides or fertilizers

used. Original extraction process (patented) for

improved slimming efficacy

Composition and efficacy are guaranteed

for each batch: dilinoleoyl-glycero-3-

phosphocholine content titrated + guaranty of slimming innovation (anti-angiogenesis

effect tested)

3364/GB/01/ JULY 2006 - 35

ADIPOLESS - STRUCTURE

Chenopodium Quinoa from Canada

-Noble plant containing no gluten called the “rice of the Incas”,with a targeted nutritional value: rich in bioavailable minerals (iron, magnesium, zinc, manganese), vitamins, essential amino acids, etc.

- High-quality ORGANIC crops

Desaponified extract, without contaminants

Purification by mechanical abrasion, vigorous washing, drying and pasteurization

More efficient extraction

ADIPOLESS

- With a titrated DLP content (dilinoleoyl-glycero-3 phosphocholine )

- Slimming efficacy guaranteed (anti-angiogenesis effect)

Original extraction process(patented)

3364/GB/01/ JULY 2006 - 36

ADIPOLESS : ANTI ADIPOGENESIS INNOVATION

No fat storage

Fat storage

ADIPOLESS inhibits the formation of new fat thanks to its anti-adipogenesis effect.

3364/GB/01/ JULY 2006 - 37


ADIPOLESSADIPOLESS

Pre Pre --Adipocytes are on a Adipocytes are on a dietdiet

ANTIANTI--ADIPOGENESIS EFFECTADIPOGENESIS EFFECT

Prevents recruitment of new adipocytes thanks to its anti-

MMP9 effect (signal promoting formation of adipose tissue)

1. ANTI ANGIOGENESIS

Inhibits neo-vascularisation

Complementary Complementary effect with effect with

ADIPOSLIM to ADIPOSLIM to maintain the maintain the

«« silhouettesilhouette » ! » !

2. ANTI MATURATION 2. ANTI MATURATION

of adipocytesof adipocytes

Adipocytes are not Adipocytes are not functional and functional and cannot cannot store fats !store fats !

Innovation

ADIPOLESS ADIPOLESS

1.1. AntiAnti--AdipogenesisAdipogenesis

INNOVATIVE EFFECT

3364/GB/01/ JULY 2006 - 39

ADIPOLESS: LESS ADIPOCYTES TO MAINTAIN YOUR “SILHOUETTE”

1.1. ANTI-ANGIOGENESIS EFFECT ( neo-vascularization)SLIMMING

INNOVATION

-100

-50

0

% angiogenesis

inhibition / control

Protocol: Quantification of the number of capillary structures on a UVEC endothelial cell culture coming from cord ombelical (able to arrange themselves in blood vessels).

Fumagillin0.0015% de

ADIPOLESS 0.01% am

-50%

-90%

⇒ ADIPOLESS limits the neo-vascularization required to nourish and generate new adipocytes (adipogenesis). Therefore it effectively

inhibits the formation of new fat.

3364/GB/01/ JULY 2006 - 40

1.2. INHIBITION OF ADIPOCYTES MATURATION (differentiation)

0

0,5

1

1,5

2

2,5

differentiation of adipocytes

(perilipin labeling)

co ntro l TNF a lpha 1ng/ml ADIP OLESS 0.02% am

Protocol: Inhibition of differentiation of 3T3-L1 pre-adipocytes into adipocytes is quantified by fluorescent labelling of PERILIPIN (SPECIFIC labelling of lipid droplets ). Their metabolic activity is evaluated by assay of the activity of G6PDH, a key enzyme in differentiation.

The Inhibition of maturation is confirmed by the inhibition of the metabolic activity of adipocytes(G6PDH unit / mg proteins ): - 100% G6PDH compared to the control with 0.02% ADIPOLESS

-91% differentiation compared to the control

* *

* P < 0.05

Differentiated fluorescent adipocytes

Non-differentiated adipocytes

1.2.1. Non-functional adipocytes:


am: active matter

3364/GB/01/ JULY 2006 - 41

1.3. MODE OF ACTION OF THE ANTI-ADIPOGENESIS EFFECT ?

Protocol: MMP9 is a metalloproteinase secreted by the adipocytes which contributes to adipocytedifferentiation and neo-vascularization (formation of adipose tissue). Inhibition of human MMP9 activity is determined by fluoro-enzymatic assay.

1.2.2. Inhibition of MMP9 (signal inducing neo-vascularization and differentiation):

-90-80-70-60-50-40-30-20-10

00 0.001 0.002 0.003 0.004 0.005 0.006

% in

hib

itio

n o

f M

MP

9 ac

tivi

ty

rela

tive

to

th

e co

ntr

ol

ADIPOLESS % am

=> By inhibiting the activity of MMP9, ADIPOLESS limits the adipogenesis process (differentiation of adipocytes and neo-vascularization). It thus prevents the formation of new fat.


am: active matter

3364/GB/01/ JULY 2006 - 42


ADIPOLESSADIPOLESS

PrePre-- Adipocytes are on a Adipocytes are on a dietdiet

ANTIANTI--ADIPOGENESIS EFFECTADIPOGENESIS EFFECT

Prevents recruitment Prevents recruitment of new of new adipocytes adipocytes thanksthanks to to its its antianti--

MMP9 MMP9 effect effect (signal promoting formation of adipose tissue)

1. ANTI ANGIOGENESIS

Inhibits neo-vascularisation

Complementary Complementary effect with effect with

ADIPOSLIM to ADIPOSLIM to maintain the maintain the

«« silhouettesilhouette » ! » !

2. ANTI MATURATION 2. ANTI MATURATION

of adipocytesof adipocytes

Adipocytes are not Adipocytes are not functional and functional and cannot cannot store fats !store fats !

Innovation

ADIPOLESS ADIPOLESS

2. Tolerance2. Tolerance

3364/GB/01/ JULY 2006 - 44

ADIPOLESS - TOLERANCE

ADIPOLESS has an excellent tolerance profile:

.Very well tolerated when topically applied

. Non-sensitizing

. Non-mutagenic

Dose recommended for total safety: up to 10% in topical cosmetic applications

ADIPOLESS ADIPOLESS

3. Formulation guidelines3. Formulation guidelines

3364/GB/01/ JULY 2006 - 46

ADIPOLESS can be incorporated from ADIPOLESS can be incorporated from 1% to 3%1% to 3% in all types of in all types of formulas for topical use. It can be easily incorporated into formulas for topical use. It can be easily incorporated into slimming projects:slimming projects:

Colorless, clear lotions, toiletry products

Hydro-soluble yellow liquid With a titrated dilinoleoyl-glycero-3-phosphocholine content

Color and odor stable over time

Non sensitive to heat and shearing – Compatible with cold process. May be incorporated before or after emulsification. Introduction to the

aqueous phase.

Does not generate electrolytes.

Compatible with caffeine, ethanol.

ADIPOLESS : FORMULATION GUIDELINES

White emulsions or creams-gels

3364/GB/01/ JULY 2006 - 47

SOS SILOUHETTE GEL 7047

Formula:

Association of ADIPOSLIM and ADIPOLESS for a curative and preventive effect against cellulite. Cold process formula.

A • SEPINOV EMT10 (Hydroxyethyl acrylate & Sodium acryloyldimethyl taurate copolymer – SEPPIC)

3.00%

• Water / Aqua Qsp 100%B • Glycerin 10.00%C • Isononyl isonanoate 4.00%

• Cyclopentasiloxane 2.00%• Phenoxyethanol 0.35%• Methyl paraben 0.15%• Ethyl paraben 0.15%

D • Ethanol 30.0%• Chlorphenesin 0.20%• Fragrance 0.10%

E • ADIPOSLIM (Sorbitan laurate and lauroyl Proline – SEPPIC) 3.00%F • NAOH (12% solution) Qs pH= 5.2G • ADIPOLESS ( Butylene glycol and Chenopodium Quinoa Seed Extract – Seppic) –) 1.00%

.

ADIPOLESS ADIPOLESS

4. Summary of key benefits4. Summary of key benefits

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ADIPOLESS KEY BENEFITS

1. Specific extract of Canadian Quinoa using an original extraction process – High-quality extract with a titrated active substance (dilinoleoyl-glycero 3 phosphocholine) content and a guaranteed anti-angiogenesis efficacy – paraben-free – PATENTED

2. Anti-adipogenesis INNOVATION thanks to an ANTI MMP9 action to prevent the formation of new fat!

=> ANTI-ANGIOGENESIS ACTION => the adipocytes are isolated and put on a diet ( neo-vascularization)=> ANTI-DIFFERENTIATION ACTION => the adipocytes are no longer capable of storing fat

3. Excellent tolerance for cosmetic applications

4. Very easily formulated (hydrosoluble extract) in ALL cosmetic projects, including transparent lotions and toiletry products –can be used to formulate colorless formulas (use from 1 to 3%)

5. Perfect cosmetic stability - compatible with caffeine and ethanol.

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Food Triglycerides (TG)

Free fatty acids (FFA)

Pre-Adipocytes (no storage of fats)Adipocytes

+60% volume

ADIPOLESS:PREVENTS THE

RECRUITMENT OF NEW ADIPOCYTES

via AN ANTI-ADIPOGENESIS

ACTION

(anti-angiogenesis + anti-maturation).

ADIPOSLIM:INHIBITS and

ELIMINATES fat storage

Recruitment and Maturation

Storage of fat (TG)

Lipogenesis (fat storage)

INNOVATIVE

ACTION

ADIPOSLIM

ADIPOSLIM

ADIPOLESS

MMP9 signals

( nutrients, ADIPOGENESIS)

ADIPOLESS

Blood vessels

+ Blood vessels

Blood vessels

Angiogenesis = neovascularization

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SOS SILHOUETTE PROGRAM –ADIPOSLIM & ADIPOLESS WINNING DUO

ADIPOSLIM ADIPOLESS

INHIBITS and ELIMINATES FAT STORAGE to get rid of existing cellulite!

“SILHOUETTE” MAINTENANCE to prevent

new fat forming!

A WINNING SLIMMING DUO

CURATIVE action: for “top model”

shape adipocytes!

PREVENTIVE action: less functional adipocytes!

Nota

The analytical specifications warranted are only those mentioned on the certificate of analysis supplied with each delivery of the product.

Except as set forth above, SEPPIC* makes no warranties, whether express, implied or statutory, as to the product which is the subject of this document . Without limiting the generality of the foregoing, SEPPIC* makes no warranty of merchantability of the product or of the fitness of the product for any particular purpose. Buyer assumes all risk and liability resulting from the use or sale of the product, whether singly or in combination with other goods. The information set forth herein is furnished free of charge and is based on technical data that SEPPIC* believes to be reliable. It is intended for use by persons having technical skill and at their own discretion and risk. Since conditions of use are outside SEPPIC*'s control, SEPPIC* makes no warranties, express or implied, and assumes no liability in connection with any use of this information. Nothing herein is to be taken as a license to operate under or a recommendation to infringe any patents.

* SEPPIC being: And, depending on the country:

SEPPIC S.A. SEPPIC UK Ltd SEPPIC ITALIA Srl75, quai d’Orsay 50 Salisbury Road Via Quarenghi 2775321 Paris cedex 07 PO Box 338 - Hounslow 20151 MilanoFRANCE TW4 6SH - ENGLAND ITALYTel.: +33 (0) 1 40 62 55 55 Tel.: +44 208 577 8800 Tel.: +39 02 38009110Fax: +33 (0) 1 40 62 52 53 Fax: +44 208 570 2106 Fax: +39 02 38009140

GIVAUDAN LAVIROTTE S.A. SEPPIC Inc. SEPPIC China56, rue Paul Cazeneuve 30, Two Bridges Road, suite 210 Room 510 Jin Tai BuildingBP 8344 – 69008 Lyon Fairfield, New Jersey 07004-1530 58 South Mao Ming RoadFRANCE USA Shanghai 200020 CHINA Tel.: +33 (0) 4 78 61 55 00 Tel.: +1 973 882 5597 Tel.: +86 (21) 64 66 01 49Fax: +33(0) 4 72 05 60 89 Fax: +1 973 882 5178 Fax: +86 (21) 64 66 11 09

SEPPIC GmbH SEPPIC Belgium NVABC Tower Köln Nieuwe Weg 1Ettore - Bugatti - Str.6-14 Haven 105351149 Köln-Porz B – 2070 ZwijndrechtGERMANY BELGIUMTel.: +49 (0) 220 3890 3100 Tel.: +32 3 250 3911Fax: +49 (0) 220 3890 3199 Fax: +32 3 250 3912

www.seppic.com

Subsidiary of the AIR LIQUIDE Group

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Documents

ADIPOSLIM: “top model” shape adipocytes to correct ... · This fat storage reduction is reinforced by the inhibition of the Lipoprotein Lipase (-22% at 0.1%am). Protocol: measurement