CN107998437A - Nanometer cross-linking hyaluronic acid sodium gel and its preparation method and application - Google Patents
Nanometer cross-linking hyaluronic acid sodium gel and its preparation method and application Download PDFInfo
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Abstract
The invention discloses nanometer cross-linking hyaluronic acid sodium gel and its preparation method and application, the particle diameter of the nanometer cross-linking hyaluronic acid sodium gel is 100nm~500nm.The nanometer cross-linking hyaluronic acid sodium gel of the present invention can enter deep skin by skin barrier, and hyaluronic acid is constantly decomposed at deep skin, deep skin is fully moistened, and can fill microgroove and make skin repair, recover elastic；Dressing, facial mask and the skin care compositions of the present invention can play moisturizing and repair skin function be by enter the cross-linking hyaluronic acid sodium of deep skin it is outer by inner, skin surface hyaluronic acid by outer and in collective effect and produce, to the long action time of skin, moisturizing and smoothing wrinkle repairing effect are more preferably.
Description
Technical field
The present invention relates to cross-linking hyaluronic acid sodium, and in particular to a kind of nanometer cross-linking hyaluronic acid sodium gel and its preparation side
Method and application, the medical dressing containing nanometer cross-linking hyaluronic acid sodium gel, the guarantor containing nanometer cross-linking hyaluronic acid sodium gel
Wet facial mask and Essence.
Background technology
Hyaluronic acid（Hyaluronic acid, hereinafter referred to as HA）For a kind of polysaccharide, its structure is by β -1,3- glucose
Acetamide（β -1,3-N-acetylglucosamine）With β-Isosorbide-5-Nitrae-gluconic acid（β-Isosorbide-5-Nitrae-glucuronic acid）With β-
1-4 is bonded to form disaccharide recurring unit, this disaccharide recurring unit is bonded with β -1-3 repeats to link again, the straight chain polymer of formation
Polymer.Commodity Sodium Hyaluronate（Sodium hyaluronate, hereinafter referred to as SH）For the sodium-salt form of HA.Hyaluronic acid is wide
General to be distributed in animal and human connective tissue extracellular matrix, its random coil state in the solution and its fluid move
Mechanics feature makes it have height viscoplasticity, plasticity, permeability and good biocompatibility.
Hyaluronic acid is naturally present in the polymer with water retaining function in human skin, be in the world it is generally acknowledged most
Good moisturizer；The water retention value of HA is about 80mL/g in connective tissue, than other any natural or synthesis polymer all
With stronger water holding capacity, it is referred to as natural moisturizing factor.In addition, HA can also become the egg of molecular weight bigger with protein binding
White polysaccharide molecule, proteoglycan molecule are to maintain the important component of moisture in loose connective tissue.It is distributed in connective tissue
Proteoglycan is combined by glycosaminoglycan with water, and the gel that this HA- protein-water is formed together, plays cell adhesion
Normal cell metabolism effect and tissue water retention, protection cell prevent from infecting, skin is had one from invading pathogens
Fixed toughness and elasticity.Based on the above-mentioned performance of hyaluronic acid, it is widely used in beautifying face, preserving moisture facial mask and medical dressing.
Either as beauty mask or medical dressing, the hyaluronic acid of straight chain is in vivo easily because of enzyme such as hyalomitome
The effect of sour hydrolase and free radical and degrade, therefore the holdup time in vivo is short.
Such as 103705971 B of Chinese patent literature CN（Application number 201310697149.5）Disclose a kind of compound
Bright matter acid wound dressing, including nonwoven layer and hyaluronic acid dressing layer, hyaluronic acid dressing layer by hyaluronic acid, vaseline,
Beeswax and carbomer composition.The dressing uses noncrosslinking hyaluronic acid, and degraded is fast in vivo, and skin wound is protected
Shield and the action time repaired are short, and moistening effect is poor, and effective time is short；And vaseline when component using when skin have greasy feeling,
Use uncomfortable.
It is crosslinked the bioactivity for not only having remained hyaluronic acid to hyaluronic acid, but also improves hyaluronic acid in vivo
Residence time.Cross-linked-hyaluronic acid has the biocompatibility identical with hyaluronic acid, and the residence time is long and with the time in vivo
Passage and be ultimately breaks down into carbon dioxide and water.Due to the crosslinking HA of the water-insoluble of cross-linked-hyaluronic acid, out of the human body portion
It can not penetrate into skin, cross-linked-hyaluronic acid need to be needed to be injected into dermal layer of the skin could play filling effect, therefore limit
The application range of cross-linked-hyaluronic acid.
102895699 A of Chinese patent literature CN（Application number 201210464125.0）A kind of skin that is used for is disclosed to create
Hinder the preparation method for the composite hydrogel dressing repaired, be that hyaluronic acid and type i collagen exist by crosslinking agent of sodium trimetaphosphate
It is chemically crosslinked under alkaline condition, composite hydrogel is obtained after cross-linking products cleaning.
104497345 A of Chinese patent literature CN（Application number 201510003731.6）Disclose a kind of hyaluronic acid-
The preparation method of the degradable dressing of chitosan, first prepares hyaluronic acid solution and chitosan solution, by hyaluronic acid and chitosan
Mixing, adds crosslinking agent and reacts to obtain hyaluronic acid-chitosan gel, gel is obtained dressing after further treatment.
Cross-linking products can only work in skin surface disclosed in above-mentioned document, it is impossible into inside skin.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of nanometer cross-linking hyaluronic acid sodium gel and preparation method thereof
And application.
The technical solution for realizing the object of the invention is a kind of nanometer cross-linking hyaluronic acid sodium gel, and the nanometer cross-linking is transparent
The particle diameter of matter acid sodium gel is 100nm~500nm.
A kind of preparation method of nanometer cross-linking hyaluronic acid sodium gel as described above, comprises the following steps：
1. by cross-linking hyaluronic acid sodium dry powder under conditions of less than 40 DEG C, input is the 25%~45% of 15~25 times of its weight
In aqueous acetone solution, stir to obtain suspension.
2. 1. suspension that step is obtained is sent into homogeneous 1~3 time, control material temperature in homogenizing process in high pressure homogenizer
≤ 45 DEG C of degree.
3. by after homogeneous material be sent into 3500~7000MWCO bag filter in, by the bag filter flowing go from
Submergence places 2 days to 3 days and completes dialysis in sub- water.
Centrifuged 4. the material 3. step is dialysed after in bag filter is sent into centrifuge, remove the clear liquid on upper strata, will
The precipitation of lower floor is taken out, and obtains nanometer cross-linking hyaluronic acid sodium gel.
A kind of nanometer cross-linking hyaluronic acid sodium gel as described above is in two class medical instrument hyaluronic acid dressings, moisturizing face
Application in film and skin care compositions.
Alternatively, skin care compositions includes acceptable tax in nanometer cross-linking hyaluronic acid sodium gel and skin care item
Shape agent, the content of nanometer cross-linking hyaluronic acid sodium gel is 0.1wt%~1.0wt%.
The skin care compositions is cream, lotion, gel, Essence, facial mask, aqua, pulvis or lotion.
A kind of medical dressing containing nanometer cross-linking hyaluronic acid sodium gel as described above, including carrier layer and reparation liquid,
To repair liquid and be impregnated with carrier layer, the weight percentage for repairing each component in liquid is 0.1 %~1% of hyaluronic acid compositions,
PBS surpluses；Hyaluronic acid compositions include 25%~30% nanometer cross-linking hyaluronic acid sodium gel and the hyaluronic acid of surplus
Gel, the hyaluronic acid derivatives are high by hyaluronic acid derivatives of 10%~20% molecular weight less than 300,000 and 80%~90% molecular weight
Hyaluronic acid derivatives in 300,000 form.
Further, repair in liquid and further include carbomer 0.05%~0.3%.
A kind of facial mask containing nanometer cross-linking hyaluronic acid sodium gel as described above, including carrier layer and Essence, elite
Liquid is impregnated with carrier layer, and the weight percentage of each component is hyaluronic acid compositions 0.1%~1% in Essence, carbomer 0.05%
~0.3%, PBS surplus；Hyaluronic acid compositions include 25%~30% nanometer cross-linking hyaluronic acid derivatives and surplus it is saturating
Bright matter acid gel, the hyaluronic acid derivatives are by hyaluronic acid derivatives of 10%~20% molecular weight less than 300,000 and 80%~90% point
Hyaluronic acid derivatives of the son amount higher than 300,000 form.
Further, which repairs facial mask for moisturizing, wherein further including collagen 0.1%~0.5%, CGF0.001%
~0.01%, EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, glycerine 4%~5%.
A kind of Essence for including nanometer cross-linking hyaluronic acid sodium gel as described above, the weight of each component in Essence
Percentage composition is hyaluronic acid compositions 0.1%~1%, collagen 0.1%~0.5%, CGF0.001%~0.01%,
EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, PBS surpluses；Hyaluronic acid compositions include 25%~30%
The hyaluronic acid derivatives of nanometer cross-linking hyaluronic acid derivatives and surplus, the hyaluronic acid derivatives are less than by 10%~20% molecular weight
The hyaluronic acid derivatives of 300000 hyaluronic acid derivatives and 80%~90% molecular weight higher than 300,000 form.
The present invention has positive effect：（1）The present invention nanometer cross-linking hyaluronic acid sodium gel particle diameter for 100nm~
500nm, the cross-linking sodium hyaluronate gel of this particle diameter can enter deep skin by skin barrier, at deep skin not
It is disconnected to be decomposed into hyaluronic acid, deep skin is fully moistened, and microgroove can be filled to make skin repair, recover elasticity；Crosslinking
Sodium Hyaluronate is to the long action time of skin, and moisturizing and smoothing wrinkle repairing effect are more preferably.
（2）The dressing containing nanometer cross-linking hyaluronic acid of the present invention, include hyaluronic acid in facial mask or skin care compositions
Composition, the hyaluronic acid compositions include the hyalomitome of nanometer cross-linking hyaluronic acid sodium gel, molecular weight less than 300,000
Acid and molecular weight are higher than 300,000 hyaluronic acid；Above-mentioned dressing, facial mask or skin care compositions can play moisturizing and repair skin function
Be by enter the cross-linking hyaluronic acid sodium of deep skin it is outer by inner, skin surface hyaluronic acid by outer and in collective effect
And produce.The hyaluronic acid of nanometer cross-linking Sodium Hyaluronate and various molecular weight synergistic effect reach optimal moisture-keeping efficacy and
Repair the effect of skin.
In addition, have in the dressing of the invention containing nanometer cross-linking Sodium Hyaluronate, facial mask and skin care compositions without other
Solvent, therefore such as dry skin, red and swollen and the problem of stimulate will not be brought.In addition, accomplished not only not containing solvent, but also
Solve the problems, such as that liquid is homogeneous scattered.
（3）The preparation method of nanometer cross-linking hyaluronic acid derivatives using the present invention obtained average grain diameter for 500nm with
Under cross-linked hyaluronic acid gel.The preparation method of the present invention is simple, reliable.
Brief description of the drawings
Fig. 1 is the particle size distribution figure of nanometer cross-linking hyaluronic acid derivatives prepared by embodiment 1.
Fig. 2 is the molecular weight and graph of molecular weight distribution of the hyaluronic acid used in embodiment 3.
Embodiment
（Embodiment 1）
The average grain diameter of the nanometer cross-linking hyaluronic acid derivatives of the present embodiment is 364nm.
The preparation method of above-mentioned nanometer cross-linking hyaluronic acid derivatives comprises the following steps：
1. by cross-linking hyaluronic acid sodium dry powder under conditions of less than 40 DEG C, input is 15~25 times of its weight（In the present embodiment
For 20 times）25%~45%（It is 40wt% in the present embodiment）Aqueous acetone solution in, stir to obtain suspension.
The cross-linking hyaluronic acid sodium dry powder is first using entitled《High quality cross-linking sodium hyaluronate gel and
Its preparation method》Chinese patent literature CN 103923328A（Application number 201410153564.9）It is prepared by disclosed method
Cross-linking sodium hyaluronate gel is obtained, then gel is dried in vacuo to obtain dry powder spare under conditions of less than 30 DEG C.
2. 1. suspension that step is obtained is sent into homogeneous 1~3 time in high pressure homogenizer（The present embodiment is 2 times）.This reality
The pressure for applying the high pressure homogenizer of example is 180Mpa.Each time during homogenization, under pressurization, high pressure suspension is rapidly
Pass through high-pressure homogeneous chamber.
Control material temperature is all the time≤45 DEG C in homogenizing process.
High pressure homogenizer used is equal for the high pressure microjet nanometer of the Microfluidizer models of MFIC companies of the U.S.
Matter machine.
3. the material after homogeneous is sent into the bag filter of 3500~7000MWCO（The rule of bag filter used in the present embodiment
Lattice are 3500MWCO）It is interior, which is submerged into placement in the deionized water of flowing and completes dialysis within 2 days to 3 days.The flowing
Deionized water have fresh deionized water supplement always.
Centrifuged 4. the material 3. step is dialysed after in bag filter is sent into centrifuge, remove the clear liquid on upper strata, will
The precipitation of lower floor is taken out, and filtering, obtains nanometer cross-linking hyaluronic acid sodium gel when dripping there is no water droplet.
Nanometer cross-linking hyaluronic acid derivatives made from the present embodiment are detected as follows：
Granularity Detection is carried out using the 2000 type particle size analyzers of Mastersizer of Malvern companies of Britain.
Cross-linking sodium hyaluronate gel 0.1g obtained above is sent into particle size analyzer detection, the size distribution measured is shown in
Fig. 1, the average grain diameter of obtained nanometer cross-linking hyaluronic acid derivatives is 364nm.
（Embodiment 2）
The average grain diameter of the nanometer cross-linking hyaluronic acid derivatives of the present embodiment is 486nm.
Remaining preparation side with the nanometer cross-linking hyaluronic acid of embodiment 1 of the preparation method of above-mentioned nanometer cross-linking hyaluronic acid
Method is identical, and difference is：
Step 1. in it is used be 30% aqueous acetone solution in.
2. 1. suspension that step obtains step is sent into homogeneous 2 times, the pressure of high pressure homogenizer in high pressure homogenizer
150Mpa。
（Embodiment 3, nanometer cross-linking Sodium Hyaluronate medical dressing）
The nanometer cross-linking sodium hyaluronate dressing of the present embodiment belongs to two class medical instruments, including carrier layer and reparation liquid, repairs
Liquid is impregnated with carrier layer, and the weight percentage for repairing each component in liquid is hyaluronic acid compositions 0.1%~1%（This implementation
It is 0.2% in example）, surplus PBS；The hyaluronic acid compositions include 25%~30%（It is 28% in the present embodiment）'s
The nanometer cross-linking hyaluronic acid sodium gel of 100nm~500nm and the hyaluronic acid derivatives of surplus, the hyaluronic acid derivatives by
10%~20%（It is 15% in the present embodiment）Molecular weight is less than 300,000 hyaluronic acid derivatives and 80%~90%（It is in the present embodiment
85%）Hyaluronic acid derivatives of the molecular weight higher than 300,000 form, and above content refers both to mass percentage.
The molecular weight and molecualr weight distribution of hyaluronic acid used in the present embodiment is analyzed, molecular weight and molecular weight point
Cloth analysis uses HPLC+GPC methods, and detector uses 2414 refractive index detection devices of WATERS, measures that the result is shown in Fig. 2.
GPC results are as follows：
GPC distribution tables are as follows：
（Embodiment 4, nanometer cross-linking sodium hyaluronate dressing）
Remaining is same as Example 3 for the nanometer cross-linking sodium hyaluronate dressing of the present embodiment, and difference is：Repair in liquid also
Including carbomer 0.05%~0.3%（It is 0.15% in the present embodiment）.
（Embodiment 5, nanometer cross-linking Sodium Hyaluronate moisture saver mask）
The nanometer cross-linking Sodium Hyaluronate facial mask of the present embodiment includes carrier layer and Essence, and Essence is impregnated with carrier layer,
The weight percentage of each component is hyaluronic acid compositions 0.1%~1% in Essence（It is 0.25% in the present embodiment）, card ripple
Nurse 0.05%~0.3%（It is 0.2% in the present embodiment）, surplus PBS；The hyaluronic acid compositions include 25%~30%（This
It is 25% in embodiment）The nanometer cross-linking hyaluronic acid derivatives of 100nm~500nm and the hyaluronic acid derivatives of surplus, it is described
Bright matter acid gel is by 10%~20%（It is 16% in the present embodiment）Molecular weight is less than 300,000 hyaluronic acid derivatives and 80%~90%
（It is 84% in the present embodiment）Hyaluronic acid derivatives of the molecular weight higher than 300,000 form.
（Embodiment 6, nanometer cross-linking Sodium Hyaluronate moisture saver mask）
Remaining is same as Example 4 for the nanometer cross-linking Sodium Hyaluronate facial mask of the present embodiment, and difference is being gone back in Essence
Including collagen, CGF, EGF, gamma-polyglutamic acid and glycerine；Wherein weight percentage of the collagen in Essence be
0.1%~0.5 %, CGF are 0.001%~0.01%, EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, and glycerine is
4%~5%.
It is by entering the cross-linking hyaluronic acid sodium of deep skin by inner that the facial mask of the present invention, which plays moisturizing and repairs skin function,
And it is outer, skin surface hyaluronic acid by outer and in collective effect and produce.In the facial mask of embodiment 5 and embodiment 6 not
Containing other organic solvents, therefore such as dry skin, red and swollen and the problem of stimulate will not be brought.In addition it is equal to also solve Essence
One it is scattered the problem of.
（Embodiment 7, nanometer cross-linking Sodium Hyaluronate skin care compositions）
The skin care compositions of the present embodiment includes hyaluronic acid compositions 0.1wt%~1.0wt%, carbomer 0.05%~0.3%
And acceptable excipient in skin care item.
（Embodiment 8, nanometer cross-linking Sodium Hyaluronate Essence）
The weight percentage of each component is hyaluronic acid compositions 0.1%~1% in the Essence of the present embodiment, collagen
0.1%~0.5%, CGF0.001%~0.01%, EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, PBS surpluses；Thoroughly
Bright matter acid composition includes 25%~30% nanometer cross-linking hyaluronic acid derivatives and the hyaluronic acid derivatives of surplus, described transparent
Matter acid gel is transparent higher than 300,000 by hyaluronic acid derivatives of 10%~20% molecular weight less than 300,000 and 80%~90% molecular weight
Matter acid gel forms.
（Test example 1, nanometer cross-linking sodium hyaluronate dressing clinical test）
In Changzhou First People's Hospital, dept. of dermatology and the selection of dept. of dermatology of the second the People's Hospital of Changzhou meet product to be tested and fit
That answers disease amounts to 120 skin trauma patients.The indication of the product to be tested refers to：The skins such as dermatitis, eczema and acne
The Dermal skin surface of a wound caused by skin problem.
First, application method.
Wounds apply the nanometer cross-linking sodium hyaluronate dressing of embodiment 3, and each 10min~15min, connects once a day
Continuous two weeks, after two weeks the next day use once..
2nd, efficiency evaluation.
As follows using dressing 7 ± 1, observation surface of a wound recovery situation after 14 ± 3,28 ± 3 days, criterion.
It is effective：The surface of a wound recovers or reduces more than 2/3（I.e. recovery rate is 66.7%）, while compared with itself normal skin, wound
Face improves substantially, close to normal skin.
Effectively：The surface of a wound reduces more than 1/3（I.e. recovery rate is 33.7%）, the surface of a wound makes moderate progress after treatment, but not yet close to just
Normal skin.
It is invalid：Surface of a wound delayed recovery is denoted as invalid without significant change, and the surface of a wound is unchanged.
3rd, safety evaluatio.
1st, safety indexes.
1-1, vital sign.
1-2, laboratory examination：Blood routine, hepatic and renal function（ALT、AST、ALP、BUN、Cr）, routine urinalysis.
2nd, the time is recorded.
2-1, vital sign：Before entering group, 7 ± 1,14 ± 3,28 ± 3 days after use first.
2-2, laboratory examination：28 ± 3 days each inspection records are once before entering group, after use first.
4th, result of the test.
First 7 ± 1 days after use（V1）：The surface of a wound recovers efficiency evaluation obvious effective rate 58.3%, and effective percentage 91.7% is invalid
Rate 8.3%.
First 14 ± 3 days after use（V2）：The surface of a wound recovers efficiency evaluation obvious effective rate 58.3%, and effective percentage 93.3% is invalid
Rate 6.7%.
First 28 ± 3 days after use（V3）：The surface of a wound recovers efficiency evaluation obvious effective rate 62.5%, and effective percentage 94.2% is invalid
Rate 5.8%.
Vital sign：Test period is normal.
Laboratory examination：Before entering group, after use first 28 ± 3 days it is without exception.
Claims (10)
- A kind of 1. nanometer cross-linking hyaluronic acid sodium gel, it is characterised in that：The particle diameter of the nanometer cross-linking hyaluronic acid sodium gel For 100nm~500nm.
- A kind of 2. preparation method of nanometer cross-linking hyaluronic acid sodium gel as claimed in claim 1, it is characterised in that including with Lower step：1. by cross-linking hyaluronic acid sodium dry powder under conditions of less than 40 DEG C, input is the 25%~45% of 15~25 times of its weight In aqueous acetone solution, stir to obtain suspension；2. 1. suspension that step is obtained is sent into homogeneous 1~3 time in high pressure homogenizer, and control material temperature in homogenizing process≤ 45℃；3. by after homogeneous material be sent into 3500~7000MWCO bag filter in, by the bag filter flowing deionized water Middle submergence places 2 days to 3 days and completes dialysis；Centrifuged 4. the material 3. step is dialysed after in bag filter is sent into centrifuge, the clear liquid on upper strata is removed, by lower floor Precipitation take out, obtain nanometer cross-linking hyaluronic acid sodium gel.
- 3. a kind of nanometer cross-linking hyaluronic acid sodium gel as claimed in claim 1 two class medical instrument hyaluronic acid dressings, Application in moisture saver mask and skin care compositions.
- 4. skin care compositions according to claim 3, it is characterised in that including nanometer cross-linking hyaluronic acid sodium gel And acceptable excipient in skin care item, the content of nanometer cross-linking hyaluronic acid sodium gel is 0.1wt%~1.0wt%.
- 5. skin care compositions according to claim 4, it is characterised in that：The skin care compositions is cream, lotion, coagulates Glue, Essence, facial mask, aqua, pulvis or lotion.
- A kind of 6. medical dressing of the nanometer cross-linking hyaluronic acid sodium gel comprising described in claim 1, it is characterised in that：Including Carrier layer and reparation liquid, repair liquid and are impregnated with carrier layer, the weight percentage for repairing each component in liquid is hyaluronic acid group 0.1 %~1% of compound, PBS surpluses；Hyaluronic acid compositions include 25%~30% nanometer cross-linking hyaluronic acid sodium gel and The hyaluronic acid derivatives of surplus, the hyaluronic acid derivatives by 10%~20% molecular weight less than 300,000 hyaluronic acid derivatives and Hyaluronic acid derivatives of 80%~90% molecular weight higher than 300,000 form.
- 7. the medical dressing of nanometer cross-linking hyaluronic acid sodium gel according to claim 6, it is characterised in that：Repair in liquid Further include carbomer 0.05%~0.3%.
- 8. a kind of facial mask of the nanometer cross-linking hyaluronic acid sodium gel comprising described in claim 1, including carrier layer and Essence, Essence is impregnated with carrier layer, it is characterised in that in Essence the weight percentage of each component for hyaluronic acid compositions 0.1%~ 1%, carbomer 0.05%~0.3%, PBS surpluses；Hyaluronic acid compositions include 25%~30% nanometer cross-linking hyaluronic acid The hyaluronic acid derivatives of gel and surplus, the hyaluronic acid derivatives are less than 300,000 hyalomitome acid cure by 10%~20% molecular weight The hyaluronic acid derivatives of glue and 80%~90% molecular weight higher than 300,000 form.
- 9. nanometer cross-linking Sodium Hyaluronate facial mask according to claim 8, it is characterised in that the facial mask is moisturizing repair surface Film, wherein further including collagen 0.1%~0.5%, CGF0.001%~0.01%, EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, glycerine 4%~5%.
- A kind of 10. Essence of the nanometer cross-linking hyaluronic acid sodium gel comprising described in claim 1, it is characterised in that Essence The weight percentage of middle each component is hyaluronic acid compositions 0.1%~1%, collagen 0.1%~0.5%, CGF0.001%~ 0.01%, EGF0.001%~0.01%, gamma-polyglutamic acid 0.1%~0.5%, PBS surpluses；Hyaluronic acid compositions include 25% ~30% nanometer cross-linking hyaluronic acid derivatives and the hyaluronic acid derivatives of surplus, the hyaluronic acid derivatives are by 10%~20% point The hyaluronic acid derivatives of hyaluronic acid derivatives of the son amount less than 300,000 and 80%~90% molecular weight higher than 300,000 form.
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