CN107998437B - Nano cross-linked sodium hyaluronate gel and preparation method and application thereof - Google Patents

Nano cross-linked sodium hyaluronate gel and preparation method and application thereof Download PDF

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CN107998437B
CN107998437B CN201610928636.1A CN201610928636A CN107998437B CN 107998437 B CN107998437 B CN 107998437B CN 201610928636 A CN201610928636 A CN 201610928636A CN 107998437 B CN107998437 B CN 107998437B
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hyaluronic acid
sodium hyaluronate
gel
linked sodium
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王慧
何浩明
管汉良
朱杰
高坚杰
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Changzhou Institute Of Materia Medica Co ltd
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Abstract

The invention discloses a nano cross-linked sodium hyaluronate gel and a preparation method and application thereof, wherein the particle size of the nano cross-linked sodium hyaluronate gel is 100-500 nm. The nano cross-linked sodium hyaluronate gel can enter the deep layer of the skin through the skin barrier, and is continuously decomposed into hyaluronic acid at the deep layer of the skin, so that the deep layer of the skin is fully moistened, and fine wrinkles can be filled to repair the skin, and the elasticity is recovered; the dressing, the mask and the skin care composition have the functions of moisturizing and repairing the skin, are generated by the combined action of the cross-linked sodium hyaluronate entering the deep layer of the skin from inside to outside and the action of the hyaluronic acid on the surface of the skin from outside to inside, have long action time on the skin and have better moisturizing, wrinkle removing and repairing effects.

Description

Nano cross-linked sodium hyaluronate gel and preparation method and application thereof
Technical Field
The invention relates to cross-linked sodium hyaluronate, and in particular relates to nano cross-linked sodium hyaluronate gel, a preparation method and application thereof, a medical dressing containing the nano cross-linked sodium hyaluronate gel, and a moisturizing mask and essence containing the nano cross-linked sodium hyaluronate gel.
Background
Hyaluronic Acid (HA) is a polysaccharide, and its structure is composed of beta-1, 3-glucosyl acetamide (beta-1, 3-N-acetylglucosamine) and beta-1, 4-gluconic acid (beta-1, 4-glucosyl acetamide) bonded by beta-1-4 bonds to form disaccharide repeating units, which are then repeatedly linked by beta-1-3 bonds to form a linear high molecular polymer. Commercial sodium hyaluronate (hereinafter abbreviated as SH) is a sodium salt form of HA. Hyaluronic acid is widely distributed in the extracellular matrix of connective tissues of animals and human bodies, and the irregular rolling state of hyaluronic acid in solution and the hydrodynamic characteristics of hyaluronic acid make hyaluronic acid have high viscoelasticity, plasticity and permeability and good biocompatibility.
Hyaluronic acid is a polymer with a water-retaining function naturally existing in human skin, and is the best humectant internationally recognized; the water retention value of HA in connective tissue is about 80mL/g, with a greater water retention capacity than any other natural or synthetic polymer, known as a natural moisturizing factor. In addition, HA can also be combined with proteins into larger molecular weight proteoglycan molecules, which are important components in retaining water in loose connective tissue. Proteoglycan distributed in connective tissue is combined with water through aminopolysaccharide, and the gel formed by HA-protein-water can adhere cells together, exert normal cell metabolism and tissue water retention, protect cells from pathogenic bacteria, prevent infection, and make skin have certain toughness and elasticity. Based on the above properties of hyaluronic acid, it is widely used in beauty moisturizing masks and medical dressings.
In both the beauty mask and the medical dressing, the straight-chain hyaluronic acid is easily degraded in the organism due to the action of enzymes such as hyaluronic acid hydrolase and free radicals, so that the residence time in the organism is short.
For example, chinese patent document CN 103705971B (application No. 201310697149.5) discloses a composite hyaluronic acid wound dressing comprising a nonwoven fabric layer and a hyaluronic acid dressing layer, the hyaluronic acid dressing layer being composed of hyaluronic acid, vaseline, beeswax and carbomer. The dressing uses non-crosslinked hyaluronic acid, is degraded quickly in a living body, has short action time on protecting and repairing skin wound surfaces, has poor moisturizing effect and short effective time; the components such as vaseline have greasy feeling when used, and are uncomfortable to use.
The cross-linking of the hyaluronic acid not only maintains the biological activity of the hyaluronic acid, but also improves the retention time of the hyaluronic acid in the body. Cross-linked hyaluronic acid has the same biocompatibility as hyaluronic acid, has a long residence time in the body and is finally decomposed into carbon dioxide and water with the passage of time. Due to the water-insolubility of the cross-linked hyaluronic acid, the cross-linked HA outside the human body cannot permeate into the skin, and the cross-linked hyaluronic acid needs to be injected into the dermal layer of the skin to play a filling role, thereby limiting the application range of the cross-linked hyaluronic acid.
Chinese patent document CN 102895699 a (application No. 201210464125.0) discloses a method for preparing a composite hydrogel dressing for skin wound repair, which comprises chemically crosslinking hyaluronic acid and type I collagen under alkaline conditions with sodium trimetaphosphate as a crosslinking agent, and cleaning the crosslinked product to obtain the composite hydrogel.
Chinese patent document CN 104497345 a (application No. 201510003731.6) discloses a method for preparing a hyaluronic acid-chitosan degradable dressing, which comprises preparing a hyaluronic acid solution and a chitosan solution, mixing hyaluronic acid and chitosan, adding a cross-linking agent to react to obtain hyaluronic acid-chitosan gel, and further processing the gel to obtain the dressing.
The crosslinked products disclosed in the above documents act only on the surface layer of the skin and do not enter the interior of the skin.
Disclosure of Invention
The invention aims to solve the technical problem of providing a nano cross-linked sodium hyaluronate gel and a preparation method and application thereof.
The technical scheme for realizing the purpose of the invention is nano cross-linked sodium hyaluronate gel, and the particle size of the nano cross-linked sodium hyaluronate gel is 100 nm-500 nm.
The preparation method of the nano cross-linked sodium hyaluronate gel comprises the following steps:
firstly, adding the crosslinked sodium hyaluronate dry powder into 25-45% acetone aqueous solution which is 15-25 times of the weight of the crosslinked sodium hyaluronate dry powder at the temperature lower than 40 ℃, and fully and uniformly stirring to obtain suspension.
Secondly, sending the suspension obtained in the step one into a high-pressure homogenizer for homogenizing for 1-3 times, and controlling the temperature of the material to be less than or equal to 45 ℃ in the homogenizing process.
And thirdly, sending the homogenized material into a dialysis bag of 3500-7000 MWCO, and immersing the dialysis bag in flowing deionized water for 2-3 days to complete dialysis.
Fourthly, the materials in the dialysis bag after dialysis in the third step are sent to a centrifuge for centrifugal separation, the supernatant is removed, and the sediment at the lower layer is taken out to obtain the nano cross-linked sodium hyaluronate gel.
The application of the nano cross-linked sodium hyaluronate gel in hyaluronic acid dressings, moisturizing masks and skin care compositions of two types of medical instruments.
Optionally, the skin care composition comprises nano cross-linked sodium hyaluronate gel and an acceptable excipient in a skin care product, and the content of the nano cross-linked sodium hyaluronate gel is 0.1wt% -1.0 wt%.
The skin care composition is cream, lotion, gel, essence, mask, aqua, powder or lotion.
The medical dressing containing the nano cross-linked sodium hyaluronate gel comprises a carrier layer and a repair liquid, wherein the carrier layer is soaked by the repair liquid, and the repair liquid comprises 0.1-1 wt% of hyaluronic acid composition and the balance of PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked sodium hyaluronate gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
Further, the repair liquid also comprises 0.05-0.3% of carbomer.
The facial mask containing the nano cross-linked sodium hyaluronate gel comprises a carrier layer and essence, wherein the essence permeates the carrier layer, and the weight percentage of each component in the essence is 0.1-1% of hyaluronic acid composition, 0.05-0.3% of carbomer and the balance of PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
Furthermore, the mask is a moisturizing and repairing mask, and also comprises 0.1-0.5% of collagen, 0.001-0.01% of CGF, 0.001-0.01% of EGF, 0.1-0.5% of gamma-polyglutamic acid and 4-5% of glycerol.
The essence containing the nano cross-linked sodium hyaluronate gel comprises 0.1-1 wt% of hyaluronic acid composition, 0.1-0.5 wt% of collagen, 0.001-0.01 wt% of CGF, 0.001-0.01 wt% of EGF, 0.1-0.5 wt% of gamma-polyglutamic acid and the balance of PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
The invention has the positive effects that: (1) the particle size of the nano cross-linked sodium hyaluronate gel is 100-500 nm, the cross-linked sodium hyaluronate gel with the particle size can enter the deep layer of the skin through a skin barrier and is continuously decomposed into hyaluronic acid at the deep layer of the skin, so that the deep layer of the skin is fully moistened, fine wrinkles can be filled to repair the skin, and the elasticity is recovered; the cross-linked sodium hyaluronate has long action time on skin and better moisturizing, wrinkle removing and repairing effects.
(2) The dressing, the mask or the skin care composition containing the nano cross-linked hyaluronic acid comprises a hyaluronic acid composition, wherein the hyaluronic acid composition comprises nano cross-linked sodium hyaluronate gel, hyaluronic acid with the molecular weight of less than 30 ten thousand and hyaluronic acid with the molecular weight of more than 30 ten thousand; the dressing, the mask or the skin care composition can play a role in moisturizing and repairing the skin, and is generated by the combined action of cross-linked sodium hyaluronate entering the deep layer of the skin from inside to outside and hyaluronic acid on the surface of the skin from outside to inside. The nanometer cross-linked sodium hyaluronate and hyaluronic acid with various molecular weights act synergistically to achieve the optimal moisturizing effect and the skin repairing effect.
In addition, the dressing, the mask and the skin care composition containing the nano-crosslinked sodium hyaluronate do not contain other organic solvents, so that the problems such as skin dryness, red swelling and irritation are not caused. In addition, the problem of uniform dispersion of liquid is solved without containing organic solvent.
(3) The cross-linked hyaluronic acid gel with the average grain diameter of less than 500nm is obtained by adopting the preparation method of the nano cross-linked hyaluronic acid gel. The preparation method is simple and reliable.
Drawings
Fig. 1 is a particle size distribution diagram of the nano-crosslinked hyaluronic acid gel prepared in example 1.
FIG. 2 is a graph showing the molecular weight and the distribution of the molecular weight of hyaluronic acid used in example 3.
Detailed Description
(example 1)
The average particle size of the nano-crosslinked hyaluronic acid gel of the present example was 364 nm.
The preparation method of the nano cross-linked hyaluronic acid gel comprises the following steps:
firstly, adding the crosslinked sodium hyaluronate dry powder into 25-45% (40 wt% in the embodiment) of acetone aqueous solution which is 15-25 times (20 times in the embodiment) of the weight of the crosslinked sodium hyaluronate dry powder at the temperature lower than 40 ℃, and fully and uniformly stirring to obtain suspension.
The cross-linked sodium hyaluronate dry powder is prepared by the method disclosed by Chinese patent document CN 103923328A (application No. 201410153564.9) named as high-quality cross-linked sodium hyaluronate gel and preparation method thereof, and then the gel is dried in vacuum at the temperature lower than 30 ℃ to obtain dry powder for later use.
And secondly, sending the suspension obtained in the step one into a high-pressure homogenizer for homogenizing for 1-3 times (2 times in the embodiment). The pressure of the high-pressure homogenizer in this example was 180 MPa. During each homogenization treatment, the high-pressure suspension rapidly passes through the high-pressure homogenization cavity under the action of pressurization.
The temperature of the materials is controlled to be less than or equal to 45 ℃ all the time in the homogenizing process.
The high-pressure homogenizer used was a Microfluidizer model high-pressure Microfluidizer, MFIC corporation, usa.
And thirdly, sending the homogenized material into a dialysis bag of 3500-7000 MWCO (the specification of the dialysis bag used in the embodiment is 3500 MWCO), and immersing the dialysis bag in flowing deionized water for 2-3 days to complete dialysis. The flowing deionized water is constantly replenished with fresh deionized water.
Fourthly, the materials in the dialysis bag after dialysis in the third step are sent into a centrifuge for centrifugal separation, the supernatant fluid is removed, the sediment of the lower layer is taken out and filtered, and the nano cross-linked sodium hyaluronate gel is obtained when no water drops drop.
The nano cross-linked hyaluronic acid gel prepared in the example was tested as follows:
particle size measurements were carried out using a Mastersizer model 2000 particle size analyzer from Malvern, uk.
0.1g of the prepared cross-linked sodium hyaluronate gel is sent into a particle size analyzer for detection, the measured particle size distribution is shown in figure 1, and the average particle size of the prepared nano cross-linked hyaluronic acid gel is 364 nm.
(example 2)
The average particle size of the nano-crosslinked hyaluronic acid gel of this example was 486 nm.
The preparation method of the nano cross-linked hyaluronic acid is the same as the preparation method of the nano cross-linked hyaluronic acid of example 1 except that:
in the step (I), a 30% acetone aqueous solution is used.
And step two, sending the suspension obtained in the step one into a high-pressure homogenizer for homogenizing for 2 times, wherein the pressure of the high-pressure homogenizer is 150 MPa.
(example 3 nanometer crosslinked sodium hyaluronate medical dressing)
The nano cross-linked sodium hyaluronate dressing of the embodiment belongs to two types of medical devices, and comprises a carrier layer and repair liquid, wherein the carrier layer is soaked by the repair liquid, and the repair liquid contains 0.1-1 wt% (0.2 wt% in the embodiment) of a hyaluronic acid composition and the balance of PBS; the hyaluronic acid composition comprises 25-30% (28% in the embodiment) of 100-500 nm nano cross-linked sodium hyaluronate gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% (15% in the embodiment) of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% (85% in the embodiment) of hyaluronic acid gel with the molecular weight higher than 30 ten thousand, and the contents refer to mass percentage contents.
The molecular weight and molecular weight distribution of the hyaluronic acid used in this example were analyzed by HPLC + GPC, and the results of measurement using a WATERS 2414 parallactic refractometer were shown in FIG. 2.
The GPC results were as follows:
Figure DEST_PATH_IMAGE001
the GPC distribution Table is as follows:
Figure 16552DEST_PATH_IMAGE002
Figure DEST_PATH_IMAGE003
Figure 579033DEST_PATH_IMAGE004
(example 4 nanometer crosslinked sodium hyaluronate dressing)
The nano cross-linked sodium hyaluronate dressing of this example was otherwise the same as example 3, except that: the repair liquid also comprises 0.05-0.3% of carbomer (0.15% in the embodiment).
Example 5 Nano Cross-Linked sodium hyaluronate moisturizing mask
The nano cross-linked sodium hyaluronate facial mask comprises a carrier layer and essence, wherein the essence permeates the carrier layer, and the weight percentage of each component in the essence is 0.1-1% (0.25% in the embodiment) of a hyaluronic acid composition, 0.05-0.3% (0.2% in the embodiment) of carbomer, and the balance of PBS; the hyaluronic acid composition comprises 25-30% (25% in the embodiment) of 100-500 nm nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% (16% in the embodiment) of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% (84% in the embodiment) of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
Example 6 Nano Cross-Linked sodium hyaluronate moisturizing mask
The rest of the nano cross-linked sodium hyaluronate facial mask of the present example is the same as that of example 4, except that the essence further comprises collagen, CGF, EGF, gamma-polyglutamic acid and glycerol; wherein the weight percentage of the collagen in the essence is 0.1-0.5%, the weight percentage of the CGF is 0.001-0.01%, the weight percentage of the EGF is 0.001-0.01%, the weight percentage of the gamma-polyglutamic acid is 0.1-0.5%, and the weight percentage of the glycerol is 4-5%.
The mask of the invention has the functions of moisturizing and repairing the skin, and is generated by the combined action of cross-linked sodium hyaluronate entering the deep layer of the skin from inside to outside and hyaluronic acid on the surface of the skin from outside to inside. The masks of examples 5 and 6 do not contain other organic solvents, and thus do not cause problems such as skin dryness, redness and irritation. In addition, the problem of uniform dispersion of the essence is solved.
Example 7 skin care composition of Nano Cross-Linked sodium hyaluronate
The skin care composition of the embodiment comprises 0.1-1.0 wt% of hyaluronic acid composition, 0.05-0.3% of carbomer and acceptable excipients in skin care products.
(example 8, Nano crosslinked sodium hyaluronate essence)
The essence comprises, by weight, 0.1% -1% of a hyaluronic acid composition, 0.1% -0.5% of collagen, 0.001% -0.01% of CGF, 0.001% -0.01% of EGF, 0.1% -0.5% of gamma-polyglutamic acid, and the balance PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
(test example 1, Nano crosslinked sodium hyaluronate dressing clinical test)
A total of 120 skin wound patients meeting the indication of the product to be tested are selected in the dermatology department of the first people hospital in Changzhou city and the dermatology department of the second people hospital in Changzhou city. The indications of the product to be tested are: superficial skin wound surface caused by skin problems such as dermatitis, eczema and acne.
Firstly, a using method.
The wound surface of the patient is applied with the nano cross-linked sodium hyaluronate dressing of example 3 for 10-15 min each time, and the nano cross-linked sodium hyaluronate dressing is continuously applied for two weeks every day and is applied every other day after two weeks. .
And II, evaluating effectiveness.
The recovery of the wound surface is observed after the dressing is used for 7 +/-1, 14 +/-3 and 28 +/-3 days, and the judgment standard is as follows.
The effect is shown: the wound surface recovers or shrinks more than 2/3 (namely the recovery rate is 66.7%), and compared with the normal skin, the wound surface is obviously improved and is close to the normal skin.
The method has the following advantages: the wound surface is reduced by more than 1/3 (namely the recovery rate is 33.7%), and the wound surface is improved after treatment, but the wound surface is not close to normal skin.
And (4) invalidation: delayed recovery or no apparent change of the wound surface was marked as ineffective, and the wound surface was unchanged.
And thirdly, evaluating safety.
1. And (4) safety indexes.
1-1, vital signs.
1-2, laboratory examination: blood regulation, liver and kidney function (ALT, AST, ALP, BUN, Cr), and urine regulation.
2. The time is recorded.
2-1, vital signs: before the treatment, 7 +/-1, 14 +/-3 and 28 +/-3 days after the first use.
2-2, laboratory examination: examination was recorded once 28. + -.3 days before group entry and after first use.
And fourthly, testing results.
7 ± 1 day after first use (V1): the wound surface recovery effectiveness evaluation has the significant efficiency of 58.3 percent, the effective rate of 91.7 percent and the ineffective rate of 8.3 percent.
14 ± 3 days after first use (V2): the wound surface recovery effectiveness evaluation has the significant efficiency of 58.3 percent, the effective rate of 93.3 percent and the ineffective rate of 6.7 percent.
28 ± 3 days after first use (V3): the wound surface recovery effectiveness evaluation has the significant efficiency of 62.5 percent, the effective rate of 94.2 percent and the ineffective rate of 5.8 percent.
Vital signs: the test period is normal.
Laboratory examination: no abnormality was found 28. + -.3 days before group entry and after first use.

Claims (10)

1. A nano cross-linked sodium hyaluronate gel is characterized in that: the particle size of the nano cross-linked sodium hyaluronate gel is 100-500 nm; the nano cross-linked sodium hyaluronate gel is swollen nano cross-linked sodium hyaluronate hydrogel;
the nano cross-linked sodium hyaluronate gel is prepared by the following method:
firstly, putting the cross-linked sodium hyaluronate dry powder into 25-45% acetone aqueous solution which is 15-25 times of the weight of the cross-linked sodium hyaluronate dry powder at the temperature lower than 40 ℃, and fully and uniformly stirring to obtain suspension;
sending the suspension obtained in the step one into a high-pressure homogenizer for homogenizing for 1-3 times, and controlling the temperature of the material to be less than or equal to 45 ℃ in the homogenizing process;
thirdly, feeding the homogenized material into a dialysis bag of 3500-7000 MWCO, and immersing the dialysis bag in flowing deionized water for 2-3 days to complete dialysis;
fourthly, the materials in the dialysis bag after dialysis in the third step are sent to a centrifuge for centrifugal separation, the supernatant is removed, and the sediment at the lower layer is taken out to obtain the nano cross-linked sodium hyaluronate gel.
2. A method for preparing nano cross-linked sodium hyaluronate gel according to claim 1, characterized by comprising the following steps:
firstly, putting the cross-linked sodium hyaluronate dry powder into 25-45% acetone aqueous solution which is 15-25 times of the weight of the cross-linked sodium hyaluronate dry powder at the temperature lower than 40 ℃, and fully and uniformly stirring to obtain suspension;
sending the suspension obtained in the step one into a high-pressure homogenizer for homogenizing for 1-3 times, and controlling the temperature of the material to be less than or equal to 45 ℃ in the homogenizing process;
thirdly, feeding the homogenized material into a dialysis bag of 3500-7000 MWCO, and immersing the dialysis bag in flowing deionized water for 2-3 days to complete dialysis;
fourthly, the materials in the dialysis bag after dialysis in the third step are sent to a centrifuge for centrifugal separation, the supernatant is removed, and the sediment at the lower layer is taken out to obtain the nano cross-linked sodium hyaluronate gel.
3. The use of the nano cross-linked sodium hyaluronate gel of claim 1 in the preparation of hyaluronic acid dressings, moisturizing masks and skin care compositions of medical devices of two types.
4. The use according to claim 3, wherein the skin care composition comprises nano cross-linked sodium hyaluronate gel and acceptable excipients in skin care products, and the content of the nano cross-linked sodium hyaluronate gel is 0.1-1.0 wt%.
5. Use according to claim 4, characterized in that: the skin care composition is cream, lotion, gel, essence, mask, aqua, powder or lotion.
6. A medical dressing comprising the nano cross-linked sodium hyaluronate gel of claim 1, characterized in that: the repair liquid soaks the carrier layer, and the weight percentage of each component in the repair liquid is 0.1-1% of hyaluronic acid composition, and the balance is PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked sodium hyaluronate gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
7. The medical dressing of nano cross-linked sodium hyaluronate gel according to claim 6, characterized in that: the repair liquid also comprises 0.05 to 0.3 percent of carbomer.
8. A facial mask comprising the nano cross-linked sodium hyaluronate gel of claim 1, which comprises a carrier layer and essence, wherein the essence is used for soaking the carrier layer, and is characterized in that the weight percentage of each component in the essence is 0.1-1% of hyaluronic acid composition, 0.05-0.3% of carbomer and the balance of PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
9. The mask according to claim 8, wherein the mask is a moisturizing and repairing mask, further comprising 0.1-0.5% of collagen, 0.001-0.01% of CGF, 0.001-0.01% of EGF, 0.1-0.5% of gamma-polyglutamic acid, and 4-5% of glycerol.
10. An essence comprising the nano cross-linked sodium hyaluronate gel of claim 1, wherein the essence comprises, by weight, 0.1% to 1% of a hyaluronic acid composition, 0.1% to 0.5% of collagen, 0.001% to 0.01% of CGF, 0.001% to 0.01% of EGF, 0.1% to 0.5% of gamma-polyglutamic acid, and the balance PBS; the hyaluronic acid composition comprises 25-30% of nano cross-linked hyaluronic acid gel and the balance of hyaluronic acid gel, wherein the hyaluronic acid gel consists of 10-20% of hyaluronic acid gel with the molecular weight lower than 30 ten thousand and 80-90% of hyaluronic acid gel with the molecular weight higher than 30 ten thousand.
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