miniHATM

New Generation Oligo

Sodium Hyaluronate

GUO XUEPING   CSOBLOOMAGE FREDA BIOPHARM CO.LTD

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)

Main content

What’s oligo

sodium hyaluronate?

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

What’s miniHATM

(纳诺HATM)?

Chemical degradation Common HA‐Oligo

H+ OH‐

OH‐OH‐

Disadvantage of chemical degradation

High specific cleavage of glycosidic bonds 

Enzymatic degradation  miniHATM

(纳诺HATM)

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

The cell proliferation ratio of cytotoxicity test

TM

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

TM

TM

Synergistic moisturizing effect of 

the combination of  miniHATM

and common HA.

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)

Thank  you!