Presentación de PowerPoint · eczema and psoriasis IL-10 Controls: Exaggerated immunological reactions (inhibits macrophages and Langerhans cells reactivity) Pro-inflammatory mediators

Physavie®

Natural soothing for the skin

Skin stress

Immune System

Inflammation

Aging Pathologies

Eczema, Dermatitis,

Psoriasis, Rosacea

UV, IIR, VL Microorganisms Pollution

Skin Immune System

• Activated by keratinocytes or direct contact with Langerhans cells (in the case of microorganisms)

• Pro-inflammatory mediators release – recruit other cells of the skin immune system such as neutrophils, macrophages and lymphocytes – releasing other pro-inflammatory mediators

Langerhans

cells Neutrophils Lymphocytes Macrophages

Pro-inflammatory mediators

IL-1

Stimulate:

IL-4, IL-5, IL-10, INF- (interferon gama) and

TNF- (tumor necrosis factor gama)

Keratinocytes and

macrophages

IL-1 TNF- Stimulate:

IL-1, IL-6, IL-8 and eicosanoides (COX-2 e PGE2)

Cause fever and ECM destruction (MMPs) and

increase vascular permeability (edema)

Atopic dermatitis

and psoriasis

ECM – Extracellular Matrix

MMPs- Metalloproteinases


IL-6

Stimulate:

Antibody production, acute phase proteins and

angiogenesis

Many cells

INF- TNF- Stimulate:

IL-2 and IL-4 and activate macrophages

(phagocytosis)

Free radicals, impair structures

psoriasis

eczema and

psoriasis

INF- - Interferon gama

TNF- - Tumor necrosis factor gama


NF-

Activates:

Cytokins and growth factors, but it posess

cyto-protective functions

Histamine

Increase:

• Allergic and atopic dermatites and sensitive skin

• Vasodilatation, edema, pruritus, pain

Atopic dermatitis,

eczema and psoriasis

IL-10 Controls:

Exaggerated immunological reactions (inhibits

macrophages and Langerhans cells reactivity)


Edema, hyperpigmentation

Vasodilatation, edema,

erythema, pain and pruritus

Growth Factors

TGF-

Stimulate:

Immune system cells migration to the region, but it

reduces the cytokine production, phagocytosis and

Langerhans cells activation

Keratinocytes, Fibroblasts

and Lymphocytes

TGF- GM-CSF Maintenance of capillary integrity and regulates

tissue repair through proliferation of fibroblasts

and synthesis of ECM components

pro- and anti-

inflammatory

action

GM-CSF - granulocyte and macrophage stimulatory factor

TGF- - tissue growth factor alfa

ECM – extracellular matrix

Aging

UVC UVB UVA

VISIBLE

IR-A IR-B IR-C

INFRARED ULTRA-VIOLET

100 nm 280 320 400 760 1mm 1400 3000

HEAT

15 min of midday sun exposition – increases

the skin temperature to 40-43ºC

6.8% 38.9% 54.3%

Source: Seo & Chung, J Dermatol Sci Suppl (2006) 2, S13-S22

Aging • Heat and visible light causes similar damages to those found in photoaging:

• MMPs

• free radicals

• inflammatory mediators

MMPs- Metalloproteinases

Physavie®

• Supercritical extract of Physalis angulata • Plant found in high solar incidence region

• Soothing properties similar to corticoids without side effects (inhibition of growth factors and acceleration of aging)

• Indicated for sensitive or sensitized skin

• Presents antiaging properties

Physavie® • In vitro tests

• Inflammatory mediators • Growth factors • Antioxidant property • Extracellular matrix

• Ex vivo tests • Extracellular matrix

• Clinical trials • Preventive study - temperature, microcirculation and TEWL • Curative study – TEWL, erythema and subjective analysis • SPF – non interference in the SPF • Permeation

Physavie® In vitro – inflammatory mediators

0

500

1.000

1.500

2.000

2.500

Controle HCTS

(0.025%)

Physavie

(0.025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

IL-6

*

*

#

&

0

200

400

600

800

1.000

1.200

Controle HCTS(0.025%)

Physavie(0.025%)

LPS(10ng/mL)

LPS +HCTS

(0.025%)

LPS +Physavie(0.025%)

pg/

mL

IL1-alfa

*

*

#

&

@ @

Keratinocytes – 48hs of incubation. LPS = bacterial lipopolysaccharides; HCTS = hydrocortisone

* p <0.001, in relation to baseline control; # p <0.05, in relation to baseline control and

HCTS; & p <0.001, relative to LPS; p <0.001, relative to LPS control and p <0.05, relative to HCTS + LPS.

Control Control



* p <0.001, in relation to baseline control; # p <0.05, in relation to baseline control; & p <0.001, in relation to baseline control and

p <0.01, in relation to HCTS; @ p <0.001, relative to LPS; £p<0.001, relative to LPS and p <0.01, relative to HCTS + LPS; $p

<0.001, in relation to LPS and p <0.05, in relation to HCTS + LPS.

0

200

400

600

800

1.000

1.200

1.400

1.600

1.800

2.000

Controle HCTS

(0.025%)

Physavie

(0.025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

TNF-alfa

0

100

200

300

400

500

600

700

800

900

Controle HCTS

(0.025%)

Physavie

(0.025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

IFN- gama

*

*

#

*

#

@ @

£

$

Control Control



. * p <0.001, in relation to baseline control; # p <0.001, relative to LPS; @P <0.001, relative to HCTS + LPS.

0

50

100

150

200

250

300

350

400

450

500

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS (10ng/mL) LPS + HCTS

(0.025%)

LPS + Physavie

(0.025%)

pg/

mL

IL-10

*

#

@

Control



* p<0,001, em relação ao controle basal; # p<0,001, em relação ao controle basal e HCTS; &p<0,001 em relação ao LPS; @P<0,001,

em relação a LPS e HCTS + LPS.

0

5

10

15

20

25

30

Controle HCTS

(0.025%)

Physavie

(0.025%)


(0.025%)

LPS + Physavie

(0.025%)

pg/

mL

Phospholipase A2

*

*

#

&

@

Control



* p <0.001, in relation to baseline control; # p <0.001, relative to LPS; & p <0.01, relative to LPS and HCTS + LPS..

0

5

10

15

20

25

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

COX-2

0

50

100

150

200

250

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

PGE-2

*

*

*

*

#

*

#

& &

Control Control



* p <0.001, in relation to baseline control; # p <0.001, in relation to baseline control and HCTS; @ p <0.001, relative to LPS; $ p <0.001,

in relation to the LPS and HCTS + LPS control..

0

5

10

15

20

25

30

35

40

45

50

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

LOX

0

200

400

600

800

1.000

1.200

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

LTB4

*

*

*

*

#

# @ @

$ $

Control Control



* p <0.001, in relation to baseline control; # p <0.001, in relation to baseline control and HCTS; @p <0.001, relative to LPS; $ p <0.001,

in relation to the LPS and HCTS + LPS control.

0

1

2

3

4

5

6

Controle HCTS (0,025%) Physavie

(0,025%)


(0.025%)

LPS + Physavie

(0.025%)

pg/

mL

Histamine

* #

*

@

$

Control



* p <0.001, in relation to baseline control; # p <0.001, in relation to the LPS control; @p <0.001, relative to LPS and HCTS + LPS.

-30

-25

-20

-15

-10

-5

0

5

10

15

20

HCTS (0,025%) Physavie

(0,025%)


(0.025%)

LPS + Physavie

(0.025%)

% r

ela

tcio

nad

o a

o c

ontr

ole

bas

al

NF-kB

*

*

*

# @

Physavie® In vitro – Growth factors


* p <0.001, in relation to baseline control; # p <0.001, in relation to baseline control and HCTS; #p <0.001, in relation to baseline

control and P <0.05, in relation to HCTS; @p <0.001, relative to LPS; $p <0.001, in relation to LPS control and HCTS + LPS..

0

500

1.000

1.500

2.000

2.500

3.000

Controle HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

TGF-beta

0

10

20

30

40

50

60

70

80

90

100

Control HCTS

(0,025%)

Physavie

(0,025%)

LPS

(10ng/mL)

LPS +

HCTS

(0.025%)

LPS +

Physavie

(0.025%)

pg/

mL

GM-CSF

*

*

#

* *

@ @

$

$

Control Control

Physavie® In vitro – antioxidant property

Keratinocytes – 48hs of incubation. HCTS = hydrocortisone; IIR/VL = infrared irradiation and visible light

* p <0.001, in relation to baseline control; # p <0.001, in relation to control and HCTS; & p <0.001, relative to IIR/VL; @ p <0.001, in

relation to the IIR/VL and IIR/VL + HCTS control..

0

1

2

3

4

5

6

7

8

9

Controle HCTS

(0.025%)

Physavie

(0.025%)

IIV/LV IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

CA

T a

ctiv

ity

(U/m

L)

CAT

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

Controle HCTS

(0.025%)

Physavie

(0.025%)

IIV/LV IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

SOD

act

ivity

(U/m

L)

SOD

*

*

#

#

*

*

*

@

&

@

Control Control IIR/VL IIR/VL IIR/VL +

HCTS

(0.025%)

IIR/VL +

HCTS

(0.025%)

IIR/VL +

Physavie

(0.025%)

IIR/VL +

Physavie

(0.025%)

Physavie® In vitro – extracellular matrix

Fibroblasts – 24hs of incubation. HCTS = hydrocortisone; IIR/VL = infrared irradiation and visible light

Gene expression was considered relevant (or significant) when values obtained in the experiment were higher than 1.5 time (±

standard deviation) or lower than 0.5 time (± standard deviation) in relation to the control.

0

0,5

1

1,5

2

2,5

3

3,5

4

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

Gene e

xpre

ssio

n in r

ela

tion t

o t

he c

ontr

ol

Colligin

0

0,5

1

1,5

2

2,5

3

3,5

4

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

Gene e

xpre

ssio

n in r

ela

tion t

o t

he c

ontr

ol

Headpin

Control Control IIR/VL

IIR/VL

IIR/VL +

HCTS

(0.025%)

IIR/VL +

HCTS

(0.025%)

IIR/VL +

Physavie

(0.025%)

IIR/VL +

Physavie

(0.025%)


0

0,5

1

1,5

2

2,5

Controle HCTS(0,025%)

Physavie(0,025%)

IIV/LV(2J/cm2)

IIV/LV +HCTS

(0.025%)

IIV/LV +Physavie(0.025%)

Gene e

xpre

ssio

n in r

ela

tion t

o the c

ontr

ol

Pro-collagen


Gene expression was considered relevant (or significant) when values obtained in the experiment were higher than 1.5 time (±

standard deviation) or lower than 0.5 time (± standard deviation) in relation to the control.

Control IIR/VL

IIR/VL +

HCTS

(0.025%)

IIR/VL +

Physavie

(0.025%)



* p <0.001, in relation to baseline control; # p <0.001, in relation to control and HCTS; & p <0.001, relative to IIR/VL; @ p <0.001, in

relation to IIR/VL and IIR/VL + HCTS control.

0

5

10

15

20

25

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

pg/

mL

Collagen type I

0

1

2

3

4

5

6

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

ug/

mL

GAG

*

*

# #

*

* *

&

@

@


IIR/VL

IIR/VL +

HCTS

(0.025%)

IIR/VL +

HCTS

(0.025%)

IIR/VL +

Physavie

(0.025%)

IIR/VL +

Physavie

(0.025%)



* p <0.001, in relation to baseline control; # p <0.001, in relation to control and HCTS; & p <0.05 and @p <0.001 relative to IIR/VL;

$ p <0.001, in relation to IIR/VL and IIR/VL + HCTS control.

0

100

200

300

400

500

600

700

800

900

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

pg/

mL

MMP-1

0

10

20

30

40

50

60

70

80

90

100

Controle HCTS

(0,025%)

Physavie

(0,025%)

IIV/LV

(2J/cm2)

IIV/LV +

HCTS

(0.025%)

IIV/LV +

Physavie

(0.025%)

pg/

mL

PMN-elastase

*

*

#

* &

@

$

$


IIR/VL

IIR/VL +

HCTS

(0.025%)

IIR/VL +

HCTS

(0.025%)

IIR/VL +

Physavie

(0.025%)

IIR/VL +

Physavie

(0.025%)

Physavie® Ex vivo – extracellular matrix

Human skin fragment – exposition to IIR/VL (2J/cm2) or oven heat at 43º C for 90 minutes. IIR/VL = infrared irradiation and visible

light.

Green fluorescence = type I collagen. Blue fluorescence = nucleus (DAPI). Band size = 50μm.

Control

Heat (43C/90 min)

Physavie®

Heat (43C/90 min)

Control

IIR/VL (2J/cm2)

Physavie®

IIR/VL (2J/cm2)

Physavie® Clinical – Preventive Study

33 volunteers 18-60 years old

Phototype I to IV

Pannel Products

Microcirculation by Laser Doppler

Cutaneous temperature

TEWL

Evaluation

Placebo

Physavie 0.5%

Hydrocortisone 0.5%

Application

1X a day for 5 days 0.1% de methyl nicotinate on D5


0255075

100125150175200225250

0 5 10 20 40

Perf

usi

on u

nits

Time (minutes after application of MN on D5)

Blood flow

Physavie 0,5% HCTS 0,5% Placebo

HCTS = hydrocortisone; MN = methyl nicotinate.


37,2 37,5 37,6 37,8 37,3

37,3 37,8 39,1

40,6

38,4

37,3 37,9

39,9

42,2

40,7

34353637383940414243

0 5 10 20 40

Skin

tem

pera

ture

(C

)

Time (minutes after application of MN on D5)

Cutaneous temperature




0

1

2

3

4

5

D1 D5

Tra

nse

pid

erm

al w

ater

loss

(T

EW

L)

(g/m

h)

Time (days)

TEWL


P>0,05 P<0,05

-21%

+5,4% P<0,05

-5,8%


Physavie® Clinical – Curative Study


Phototype I to III

Pannel Products

Erythema by Mexameter

TEWL

Subjective evaluation

Evaluation

Placebo

Physavie 1%

Hydrocortisone 1%

Application

Tape stripping in the forearm

Lactic acid 10% at nasolabial region

One single application after insult

Physavie® Clinical – Curative Study Tape stripping

-35,00

-30,00

-25,00

-20,00

-15,00

-10,00

-5,00

0,00

T2h T6h T24h T48h T72h

% c

han

ge in t

he t

ranse

pid

erm

al w

ater

loss

TEWL

Placebo Physavie 1% HCTS 1%

*

*

HCTS = hydrocortisone

* p <0.001, relative to placebo and HCTS within the times assessed; # p <0.001, in relation to control

and HCTS; # p <0.05, relative to placebo..

#


HCTS = hydrocortisone

p <0.05, in relation to HCTS at the time evaluated.

-1,5

-1

-0,5

0

0,5

1

T2h T6h T24h T48h T72h

% c

han

ge in e

ryth

em

a Mexameter

Placebo Physavie 1% HCTS 1%

*


HCTS = hydrocortisone.

0

5

10

15

20

25

30

% Im

pro

vem

ent

Subjective Evaluation

HCTS 1% Physavie 1%

T2h T6h

Physavie® Clinical – Curative Study Lactic acid

p£ 0.001, relative to placebo and, p <0.05, over placebo at the time evaluated..

-2

-1,5

-1

-0,5

0

0,5

1

T1 T2 T4

% c

hange in r

ela

tion t

o p

lacebo

Erythema

-29

-28

-27

-26

-25

-24

-23

T1 T2 T4

% c

han

ge in

rel

atio

n t

o p

lace

bo

TEWL

*

*

*

#

70% of the panel stated that there was no very mild/mild

discomfort when tested and then treated with Physavie®

Physavie® Clinical – SPF


Phototype I to III

Pannel Products

Erythema by Chromameter

T0 and T24 hours after

exposition

Evaluation

Placebo

Physavie 1%

Hydrocortisone 1%

Application

1X before exposition to 6 different

doses of UVB

Physavie® Clinical SPF

Product Mean Minimal Erythema Dose

(unprotected skin)

Mean Minimal Erythema Dose

(protected skin)

Placebo 1,76 2,48

Physavie 1% 1,76 2,44

HCTS 1% 1,76 2,45

Physavie® does not interfere with erythema

measurement, necessary for determining the

sun protection factor.

HCTS = hydrocortisone.

Physavie® Clinical - Permeation

2 volunteers

Pannel Products

Raman spectroscopy

1-60 m depth

Standard: total phytosterols (

95% pure)

Evaluation

Placebo

Physavie 1%

Application

One single application

Physavie® Clinical - Permeation

30min 1h 2h 4h 24h 48h 72h

1% Physavie® 5,884 36,173 16,916 25,426 14,844 20,152 22,429

Permeation of the active ingredient (arbitrary unit) relative

to the concentration of total phytosterols and placebo

Physavie®

Benefits

• 100% biodegradable

• Has soothing properties equivalent to hydrocortisone without the adverse effects

• Has anti-pruritic and soothing properties, essential for sensitive and/or sensitized skin

• Regulates skin temperature and microcirculation, maintaining its baseline levels, even after external aggression

Physavie®

Benefits

• Biologically reduces damage from infrared radiation and visible light;

• Has proven Anti-Aging Thermal Action;

• Can be associated with photoprotectors, with the appeal of reducing the damages caused by rays in the infrared wavelength and visible light, without interfering in the formation of erythema, needed in Solar Protection Factor (SPF) determination

Physavie® Application • Oil phase at a maximum of 80°C (for up to 15 minutes)

• pH 4,5-7,5

• Emulsions, gels, serums, tonics, soaps, oils for sensitive or sensitized skin

• Compatible with formulations containing both chemical and physical sunscreens

• For transparent formulas, please order specific version

Concentration of use 0.5-1.0% (w/w)

Thank you!

Documents

Presentación de PowerPoint · eczema and psoriasis IL-10 Controls: Exaggerated immunological reactions (inhibits macrophages and Langerhans cells reactivity) Pro-inflammatory mediators