Post on 31-Jan-2022
公司名称更改 CHANGE OF COMPANY NAME
华熙福瑞达生物医药有限公司BLOOMAGE FREDA BIOPHARM CO. LTD
山东福瑞达生物医药有限公司
SHANDONG FREDA BIOPHARM CO. LTD
NEW
股东组成 SHARE HOLDERS
华熙国际BLOOMAGE
INTERNATIONAL
华熙生物科技(HK00963)BLOOMAGE
BIOTECH
华熙福瑞达生物医药有限公司BLOOMAGE
FREDA BIOPHARM
山东福瑞达医药集团SHANDONG
FREDA
PHARMACEUTICAL
GROUP
95% 5%
Bloomage Freda
A professional manufacturer with over 20 years experience in sodium
hyaluronate (HA) industry
Providing high purity HA products, including injection grade, medical
grade, cosmetic grade and food grade.
The largest HA manufacturer in the world, with 60 tons of annual output.
Over 70% market share in China
The products have been exported to more than 40 countries, including Europe, Asia, North America.
A Business office was established in USA.
2011年HA销量比例
Marketing Overview
Bloomage
Freda’s 2 CONTRIBUTIONS TO HA INDUSTRY
1990, first developed bacteria fermentation for HA manufacture in China, which lead to the large quantity,
high quality and low cost manufacture of HA, and wide application of HA in cosmetics, pharmaceuticals and
health foods.
2011, first developed ENZYME CUT TECH for oligo‐HA manufacture in the world, which lead to the
innovation of miniHATM
(纳诺HATM)
1.8M 1M 10K
HA‐OligoHA (high Mw)
N<25
Physical property:
moisture retention
viscoelasticity
lubricity
Bioactivity:promoting angiogenesispromoting cell proliferationinitiating wounded healingantioxidant activity.
molecular weight (Da)
HA (middle Mw) HA (low Mw)
Physical property:moisture retention
400
high purity, no structural
changes
No.1
reaction conditions:
moderate, neutral pH,
35‐50℃
No.2
environment
friendly
No.3
Advantage of enzymatic degradation
Bloomage Freda Biopharm is the first and only manufacturer in the world to use enzymatic degradation in large scale production of HA‐Oligo.
15
Enzyme
miniHATM
(纳诺HATM) 10~20nm
bacteria A
bacteria B
HA
Manuf. process of miniHA Patent pending…
Test Specification
Appearance White powder
Infared spectrum comparable with Ph. Eur. reference spectrum of sodium
hyaluronate
Molecular weight 3,000~10,000
pH 6.0~8.0
Purity ≥95%
Specifications of miniHATM
(纳诺HATM)
Why do we choose miniHATM
(纳诺HATM)?
High purity, keep the integrity of HA structure
High safety
Transdermal absorption
Similar moisturizing effect as HA
High antioxidation activity
Strong effect for after sun repair
Sample Degradation method
purity(cabazole method)/%
miniHATM-1 Hyaluronidase 98.58
miniHATM-2 Hyaluronidase 99.71
miniHATM-3 Hyaluronidase 99.23
miniHATM-4 hyaluronidase 98.62
HA-Oligo-C1 Chemical 96.12
HA-Oligo-C2 Chemical 96.44
HA-Oligo-C3 Chemical 95.51
purity(HPLC method) /%
97.66
98.02
98.52
97.79
62.35
67.65
63.23
High purity
Wave number (cm‐1)Wave number (cm‐1)
Ph. Eur.
reference
spectrum of
sodium
hyaluronate
HA‐Oligo by
chemical
degradation
miniHATM
common HA
The infared spectrum of
miniHATM
was confirmed
with Ph. Eur. reference
spectrum of sodium
hyaluronate
, while that of HA‐Oligo
by chemical degradation
was obviously different.
Complete structure
Method
According to method of the cytotoxicity test
(GB/T16886.5, GB/T14233.2), this test was carried out.
Cell strain
Mouse fibroblast L929
Sample
0.5% solution of HA‐Oligo
Operation Adding sample Cell culture
Detecting cell proliferation ratioObserving cell morphology
Cell culture
High safety ‐
Cytotoxicity test
Complete medium Complete medium+phenol
Complete medium+miniHATM
The micrographs of cytotoxicity test
Complete medium+HA-Oligo by chemical degradation
Degree Grade Cutaneous reaction Volunteers
‐ 0 negative 30
± 1 Weak erythema、Xerosis cutis、Wrinkle 0
+ 2 Erythema、Edema、Papula、Wheal、
Desquamation、Cracks0
++ 3 Obvious erythema、Edema、Phlycten 0
+++ 4 Severe erythema、Edema、Bleb、Erosion、
Hyperpigmentation or hypopigmentation、
Acne kind change
0
High safety –
skin patch test
30 healthy persons were as volunteers;
0.5ml of test sample(1.0% solution of miniHATM) was applied on the flexible
forearm (5×5cm2) twice a day for seven days.
(2) There are pores of sweat
glands, sebaceous glands and
hair follicle on skin surface.
Transdermal absorption
(1) The gap among cells of
human skin surface is about
40~50nm.
O
C O O H
HO H
H O H
H
H
H O
C H2 O H
H
H N H C O C H 3
H
O H H
H
OO
n
O
C O O H
HO H
H O H
H
H
H O
C H2 O H
H
H N H C O C H 3
H
O H H
H
OO
n
N<25
about 1 nm
Average molecule size: less than 25nm
Theoretically, miniHATM
can
penetrate
into
human skin.
0
5
10
15
20
25
30
35
40
45
Cor
neom
eter
val
ue (%
)
before 1 2 4 6 8
Time (h)Control HA (Mw:1,630,000)
05
1015202530354045
Cor
neom
eter
val
ue (%
)
before 1 2 4 6 8
Time (h)
Control nanoHAminiHATM
Similar moisturizing effect as HA
Method 3.0±0.1 mg/cm2 of control and test sample were respectively
applied on the left and right forearm (4×4cm2).
Samples The only difference between control and test samples is the
formula of test samples contain test ingredients.
Volunteers 30 healthy volunteers of 20~50 years old
20
25
30
35
40
45
50
55
before 1 2 4 6 8Time (h)
Cor
neom
eter
val
ue (%
)Cont rol0.1% nanoHA0.2% nanoHA0.5% nanoHA
The higher concentrations of miniHATM
is,
the better moisture retention.
miniHATM
miniHATM
miniHATM
0
5
10
15
20
25
30
35
40
DPP
H sc
aven
ging
rate
(%)
nanoHA 5 39 76 126
Molecular weight (×104Da)
miniHATM
0.000.050.100.150.200.250.300.350.400.450.50
Abs
orpt
ion
valu
e (7
00nm
)
nanoHA 5 39 76 126
Molecular weight (×104Da)
miniHATM
The lower the molecular weight of HA is,
the higher antioxidation activity.
High antioxidation activity
Cell strain
Mouse fibroblast L929
Samples
0.06% solution of HA with different molecular weight
Strong effect for after sun repair
Operation
Adding samples
Cell culture
Cell culture
Detecting cell proliferation ratio
Observing cell morphology
Ultraviolet irradiation
Not irradiation group
miniHA TM group HA-1.61M Da group
Irradiate group
The micrographs of after sun repair test
The result shows that miniHATM
can repair the cell injury by ultraviolet irradiation.
The cell proliferation ratio after UV irradiation
Application
Moisturizer, anti‐aging agent, after sun repair, sunblock
Dosage form
Aqueous solution, gels, cream, emulsion, etc.
Recommended usage
0.1~0.5%.
Much better efficacy when combined with common HA.
Use method
Good solubility in water,
good stability in any process of cosmetics manufacture.
Direction of miniHATM
(纳诺HATM)