with New data / Short version

Alpinia Katsumadai Seed Extract

ICHIMARU PHARCOS CO.,LTD.

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1st Edition on January 21, 2010
Revised on Sep 11, 2012
1
Mechanism

Melanogenetic Balance
Accelerator Brake

Homeostasis
Cellular functions

Positive signals Negative signals

Cell

Melanocytes

2
Mechanism

Melanogenetic Balance
Melanogenic
Melanogenic Stimulators
Stimulators
from
from UV-irradiared
UV-irradiared keratinocytes
keratinocytes
Brake
ET-1 -MSH
SCF NO
Negative
Intracellular
signals

Positive
Intracellular Step on
Signals Accelerator (PLD1
(PLD1 signal)
signal)

Melanin Synthesis Cell

Melanocytes

3
Mechanism

Melanogenetic Balance
Positive Step on Brake
Intracellular
Signals
Accelerator
Negative
Intracellular
signals
Melanin
Melanin Synthesis
Synthesis

Cell (PLD1
(PLD1 signal)
signal)

Melanocytes

4
Mechanism

PLD-mTOR-S6K1 signaling
participates in the negative
Stimulators of melanogenesis regulation of melanogenesis through
(MSH,
MSH, ET, SCF, PGEs,
PGEs, NO etc)
Keratinocytes the down-regulating expression of
melanogenic enzymes
Down-regulation
R
S6K1 PA
Melanocytes mTOR PLD1 Activation
Mitf-M

Melanogenic enzymes
Tyrosinase, Tyrp1, Dct

(Ohguchi,
Melanin biosynthesis J. Cell Physiology,
2005)

5
Mechanism

PLD Novel strategy for whitening skin

through the activation of PLD1
PA Activation signaling in melanin synthesizing cell.
mTOR
ALPINIAWHITE activated PLD1-
S6K1
mTOR-S6K1 signaling in B16.
Tyrosinase (mRNA)
phospho-p70S6K1
Tyrosinase (protein)

Tyrosinase (activity)
0 0.25 0.5 (%)
Melanogenesis
Alpinia katsumadai seed extract

6
Origin / Active substance

Alpinia katsumadai Seed

Alpinia katsumadai is a member of the ginger family,
which has green, diamond-shaped leaves and round yellow
fruit, which changes color from green to yellow as it ripens.
The parts of the plant used in herbal preparations are the
seeds. After the fruit is gathered and dried in the sun, the
seeds are removed from the fruit, then smashed or ground
into a powder.
In traditional Chinese medicine, katsumadai seed has
pungent and warm properties, and is associated with the
Spleen and Stomach meridians. Its main functions are to
promote circulation of GI tract.
Alpinia katsumadai seed is used to treat conditions such
as stomachache, diarrhea and nausea. It is often used with Alpinia katsumadai
other herbs such as cinnamon bark and ginger.

7
Origin / Active substance

Cardamonin / Purification
HO OH Purification
Before After

O O
CH3 CAS No. : 19309-14-9
Molecular Formula: C16H14O4
Molecular Weight: 270.284

Cardamonin (2',4'-dihydroxy-6'-methoxychalcone), one Crude Extract

of the main constituents from Alpinia katsumadai seeds,
belongs to chalcone with its antibacterial, anti- Cardamonin
inflammatory and other important therapeutic activities 100 micro-g/mL 100 micro-g/mL
of significant potency and low systemic toxicity.

8
Test in vitro (B16)

ALPINIAWHITE suppressed expression of tyrosinase

mRNA (A) and protein (B) in B16 melanoma cells

(A) (B)

Tyrosinase Tyrosinase

0 0.25 0.5
G3PDH

0 0.25 0.5

9
Test in vitro (B16)

Inhibitory Effect of
B16 Melanoma Cells
Control
ALPINIAWHITE
25μg/mL Arbutin

0.25% Alpiniawhite
0.5% Alpiniawhite

0 0.5 1 1.5 2
ABS 420 nm control
ALPINIAWHITE diminished melanin content
in B16 melanoma cells

10
Test in vitro (B16)

ALPINIAWHITE showed much less melanin-synthesis

than other cosmetic ingredients in B16 melanoma cells

Control α-Arubutin Tranexamic acid

Sample dose:0.5%

11
Test in vitro (Human Melanocyte)

Inhibitory Effect of
Human Melanocytes
Control Human melanocytes
were incubated with
50μg/mL Arbutin ALP for 72hr in
0.25% Alpiniawhite melanocyte growth
medium (Cell
0.5% Alpiniawhite APPLICATIONS, INC.).

0 0.05 0.1 0.15

ABS 420 nm

12
Test in vitro (Human Melanocyte)

Inhibitory Effect of
Human Melanocytes (3D moel)
Control

0.25% Alpiniawhite

0.5% Alpiniawhite

0 0.5 1 1.5
Control 0.25% 0.5% ABS 420 nm
DAY11 Melanin contents

13
Clinical Test #1

UV
Clinical Test #1
UV UV

DAY -2 -1 0 1 2 3 7 14 28 41 42

UV(1 MED:Minimum Erythema Dose)

Application of Sample (cream +/- 5% ALPINIAWHITE)
Observation with Mexameter (DAY14,28,42)
Solar Simulator
Volunteers
(n=13, men)

14
Clinical Test #1

Melanin Index between

Cream with Alpiniawhite and Placebo
ALPINIAWHITE prevented UV-induced hyperpigmentation
160 (*p<0.05)
* * *
150
Melanin index

140
130
120 cream (Contorl)

110 cream with 5% ALPINIAWHITE

N=13
100
0 7 14 21 28 35 42
DAY

15
Clinical Test #1

Application of Cream with

Alpiniawhite Prevented Suntanning
DAY42
Volunteer A:40s ♂

Control

DAY42
Volunteer B:30s ♂

Control

DAY42
Volunteer C:30s ♂

Control

16
Clinical Test #1

Alpiniawhite reduced Melanin

Particles in Cornified Layer
Cornified layer (Volunteer A) Day42

Control

Cornified
Cornified layers
layers at
at Day42
Day42 were
were tape-stripped
tape-stripped and
and stained
stained with
with gentian
gentian violet.
violet.

17
Clinical Test #2

Clinical Test #2
Period ： January 11 to February 10, 2012

Subject ： 20’s to 50’s (average 38.3 years old) 10 people /Male and Female

Sample : Lotion containing 1% ALPINIAWHITE

Control : Lotion containing 1% of BG 70% sol.

Method : Apply twice a day (Morning and Evening) on half face for one month

Evaluation :
-Clarity = Chroma Meter Difference with Colorimeter / CR-400 (Konica Minolta)
-Pigmented spot = VISIA™ Evolution（Canfield）

18
Clinical Test #2

Clarity improved by ALPINIAWHITE

103
ｐ＜0.1
(Rerated value)

102
L値（相対値）

コントロール
Control
101 ALPINIAWHITE 1%
アルピニアホワイト
L [Clarity]

100

99
0w 4w

19
Clinical Test #2

Pigmented spot decreased by ALPINIAWHITE

spot (Rerated value)

110
シミ面積（相対値）

コントロール
Control
100 ALPINIAWHITE 1%
アルピニアホワイト
Area of pigmented

Area of pigmented
spots decreased
90 6% in 4 weeks
0w 4w

20
Clinical Test #2

Pigmented spot decreased by ALPINIAWHITE

30’s / Male

0w 4w

21
Other tests in vitro

ALPINIAWHITE stimulated
Differentiation in Keratinocytes
CaCl2
0 0.125 0.25 0.5 1.2mM

TGase-1

Involcrin

22
Other tests in vitro

Inhibitory Effect of NO production

120
120 120
120

NO Concentration (%)
NO Concentration (%)

100
100 100
100
80
80 80
80
60
60 60
60
40
40 40
40
20
20 20
20
00 00
00 0.5
0.5 11
22 44 88 00 0.45
0.45 0.9
0.9 1.8
1.8
Cardamonin (μg/mL) (%)
LPS 2 micro-g/mL LPS 2 micro-g/mL
Anti-redness effect of ALPINIAWHITE can be
expected against sunburned skin.

23
Registration Status / Specification

Registration Status
Latin name : Alpinia katsumadai Hayata（Zingiberaceae）
Part of Use : Seed
INCI Name : Alpinia Katsumadai Seed Extract Water, Butylene Glycol
CAS Number : 1002122-29-3, 7732-18-5, 107-88-0
EC Number : 483-930-3, 231-791-2, 203-529-7
Japan status : Not for Cosmetic | QD additive (ICHIMARU’s application)
China status : Not listed in 2007 | Listed in 2010

24
Registration Status / Specification

Product Specification
Subject Specification
Appearance
･ Color Light yellow liquid
･ Odor Characteristic odor
Identification
･ Phenolic substance Positive
･ Cardamonin Positive
pH 4.5 - 6.5
Purity Test
･ Heavy Metals 20 ppm max.
･ Arsenic 2 ppm max.
Residue on Evaporation 0.3 w/v% max.
Composition
･ Butylene Glycol 69.9 %
･ Water 29.9 %
･ Alpinia katsumadai seed Extract 0.20 %

25