CN115804730A - Sodium hyaluronate composition and preparation method and application thereof - Google Patents
Sodium hyaluronate composition and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a sodium hyaluronate composition and a preparation method and application thereof. The composition comprises a chitosan derivative and sodium hyaluronate, wherein the chitosan derivative comprises: (1) a chitosan backbone; (2) a group a linked to the main chain by an ether bond; and (3) a group B attached to the backbone via an amide bond, wherein the group a has one or more hydroxyethyl groups and the group B has one or more acyl groups and one or more amino groups. The composition provided by the invention has high sodium hyaluronate transdermal permeability and wide application prospect in the field of skin care products.
Description
Technical Field
The invention relates to a sodium hyaluronate composition and a preparation method and application thereof.
Background
It is known that the skin condition of a person changes with age and environment, and the skin condition also changes obviously, such as: the skin becomes dull, wrinkled, sensitive, pigmented, etc. To improve the condition of the skin, a number of skin care methods have been developed. Among these skin care methods, skin moisturization is the most basic and important. The currently common skin care and moisturizing way is to apply effective ingredients with moisturizing function, such as: glycerin, polysaccharide, sodium hyaluronate, and oil phase ingredients such as: shea butter, jojoba oil, cetostearyl alcohol, and the like. Among these moisturizing ingredients, substantially all of the moisturizing and moisturizing of the stratum corneum remains. However, 70% of the water in the skin is in the dermis, so how to achieve deep moisturizing of the dermis is important for moisturizing the skin. Currently, for moisturizing deep skin, the adopted method is limited, and the most common method is to directly introduce moisturizing ingredients into a real cortex layer by microneedle injection, or to penetrate the skin by using a roller pin or introduce the moisturizing ingredients into the skin by using a skin patch, so as to achieve the effect of deep moisturizing. However, the use of the above method causes pain to the user, and the long-term use causes skin sensitivity. If the problem of deep water replenishing can be solved by a smearing mode, the water replenishing and moisturizing cream has important significance for the water replenishing and the moisturizing of the skin.
Of the many moisturizing ingredients, sodium hyaluronate is of greater interest. Sodium hyaluronate is an inherent component and widely exists in tissues and organs such as articular cartilage and skin dermis. Therefore, has good biocompatibility and safety. On the other hand, sodium hyaluronate is the best humectant due to its unique property of absorbing the highest moisture at low relative humidity and the lowest moisture at high relative humidity, as compared with other humectants.
Sodium hyaluronate currently in use is generally classified into high molecular weight (> 100 ten thousand Da), medium molecular weight (20-40 ten thousand Da), low molecular weight (< 3 ten thousand Da), and smaller molecular weight (< 1 ten thousand Da). The water absorption capacity and the molecular weight of the sodium hyaluronate are closely related. The greater the molecular weight, the greater the water uptake. Therefore, the high molecular weight sodium hyaluronate has better moisturizing effect. However, it is difficult to directly permeate the skin because of its high molecular weight.
Research shows that sodium hyaluronate nano microspheres are formed by crosslinking sodium hyaluronate, so that the transdermal efficiency of sodium hyaluronate is improved [ CN113388168A; CN107998437B ]. On the other hand, the prepared cross-linked sodium hyaluronate is dissolved in water to prepare nano-scale sodium hyaluronate particles, and the nano-scale sodium hyaluronate particles are used in skin care products to realize transdermal absorption of sodium hyaluronate [ CN110559261A ]. Crosslinking sodium hyaluronate into sodium hyaluronate nanoparticles by using an ionic crosslinking agent, thereby promoting transdermal absorption of the drug [ CN105232449B; CN104958251B; CN107998437A ]. However, hyaluronic acid prepared by crosslinking is susceptible to the metabolic rate after entering the body due to the use of a crosslinking agent.
Disclosure of Invention
In order to solve one of the above-mentioned technical problems of the prior art, the present applicant prepared a complex by combining sodium hyaluronate with the high charge of a chitosan derivative based on the synthesis of the derivative, and formed nano sodium hyaluronate. And the resistance caused by the compact structure of the horny layer is reduced by utilizing the functional modification of the surface of the chitosan nano-particles, so that the percutaneous absorption of the sodium hyaluronate is promoted, and the anti-aging effect of sodium hyaluronate functional substances is further exerted. To this end, the present application is presented.
In a first aspect, the present invention provides a sodium hyaluronate composition comprising a chitosan derivative and sodium hyaluronate, said chitosan derivative comprising: (1) a chitosan backbone; (2) a group a linked to the main chain by an ether bond; and (3) a group B attached to the backbone via an amide bond, wherein the group a has one or more hydroxyethyl groups and the group B has one or more acyl groups and one or more amino groups.
According to an embodiment of the invention, the weight ratio of chitosan derivative to sodium hyaluronate molecules is 1:0.01-10, such as 1:0.01,1:0.1,1:0.2,1:0.5,1:1,2:1,3:1,4:1 or 5:1.
according to an embodiment of the invention, said chitosan derivative and said sodium hyaluronate form a nanoparticle. Sodium hyaluronate of various molecular weights may be used in the present invention. In some embodiments, the sodium hyaluronate has an average molecular weight of 1000 to 300 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of 1000 to 100 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of 2 to 100 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of 100 to 300 million Da. In some embodiments, the sodium hyaluronate has an average molecular weight of 10 to 50 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of 20 to 40 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of <3 ten thousand Da. In some embodiments, the sodium hyaluronate has an average molecular weight of <1 million Da.
According to an embodiment of the present invention, the chitosan derivative has at least one of the following structural units 1,2, and 3:
wherein in the structural units 1,2 and 3, A represents the group A, and B represents the group B.
In some embodiments, the chitosan derivative has the structural units 1 and 2. In some embodiments, the chitosan derivative has the structural unit 3. In some embodiments, the chitosan derivative has the structural units 1,2, and 3.
According to an embodiment of the invention, the group a is a polyethylene glycol group. The polyethylene glycol group may have an average molecular weight of 164-5000Da. In some embodiments, the polyethylene glycol group may have an average molecular weight of 200Da, 500Da, 1000Da, 1500Da, 2000Da, 2500Da, 3000Da, 3500Da, 4000Da, 4500Da, 5000Da, or a range between any two of these values.
According to an embodiment of the invention, the group a has the following structure:
m≥1。
according to an embodiment of the invention, m ranges from 1 to 100, such as 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or a range between any two of these values.
According to an embodiment of the invention, the group B is a group formed by an amino acid or polypeptide molecule minus one hydroxyl group. Preferably, the amino acid is selected from one or more of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and histidine. Preferably, the polypeptide is selected from one or more of a dipeptide, tripeptide or tetrapeptide.
According to an embodiment of the invention, the group B has the following structure:
，
wherein carbonyl C = O is attached to the chitosan backbone.
According to an embodiment of the invention, the group B is
。
According to an embodiment of the invention, the chitosan derivative has an average molecular weight of 500-18000Da, preferably 537-18000Da, in some embodiments the chitosan derivative may have an average molecular weight of 550Da, 600Da, 650Da, 800Da, 900Da, 1000Da, 1200Da, 1500Da, 2000Da, 2500Da, 3000Da, 3500Da, 4000Da, 4500Da, 5000Da, 6000Da, 8000Da, 9000Da, 10000Da or a range between any two of these values.
According to an embodiment of the present invention, the method for preparing the chitosan derivative comprises the steps of:
(a) Reacting chitosan with a compound containing a group A to obtain chitosan grafted with the group A;
(b) And carrying out condensation reaction on the chitosan with the grafting group A and a compound containing a group B to obtain the chitosan derivative.
In some embodiments of the invention, the compound containing group a is methoxypolyethylene glycol oxirane. Preferably, the methoxypolyethylene glycol oxirane has an average molecular weight of 176-5000Da. In some embodiments, the methoxypolyethylene glycol oxirane has an average molecular weight of 1000-2500Da. In some embodiments, the methoxypolyethylene glycol oxirane has an average molecular weight of 1500-2000Da.
In some embodiments of the invention, the group B-containing compound is an amino acid or polypeptide, preferably the amino acid is selected from one or more of the group consisting of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and histidine. Preferably, the polypeptide is selected from one or more of a dipeptide, tripeptide or tetrapeptide.
In some embodiments of the invention, the compound containing group B is arginine or histidine. In some embodiments, the compound containing group B is arginine.
In some embodiments of the invention, in step (a), the temperature of the reaction is up to 0-95 ℃, preferably 0-4 ℃; and/or for a period of 0.5 to 24 hours.
In some embodiments of the invention, in step (a), the molar ratio of chitosan to methoxypolyethylene glycol oxirane is from 1.1 to 1.
In some embodiments of the invention, EDC and NHS are used as condensing agents in step (b).
Preferably, the molar ratio of the group B-containing compound to the EDC is 1:1-1.5.
Preferably, the molar ratio of the group B-containing compound to the NHS is 1:1-1.5.
In some embodiments of the invention, in step (b), the condensation reaction is at a temperature of 0 to 4 ℃ and/or for a time of 0.1 to 24 hours.
In some embodiments of the invention, in step (a), the chitosan has an average molecular weight of 537-18000Da and in some embodiments, the chitosan may have an average molecular weight of 550Da, 600Da, 650Da, 800Da, 900Da, 1000Da, 1200Da, 1500Da, 2000Da, 2500Da, 3000Da, 3500Da, 4000Da, 4500Da, 5000Da, 6000Da, 8000Da, 9000Da, 10000Da or a range between any two of them, such as 1000-10000da,1000-5000Da, or 1000-3000Da.
In some embodiments of the present invention, the chitosan used in step (a) is obtained by a preparation method comprising the steps of: a1, hydrolyzing chitin to obtain a deacetylated product; and a2, carrying out oxidative degradation on the deacetylation product to obtain the chitosan.
In some embodiments of the invention, in step a1, the hydrolysis conditions comprise dissolving chitin in an acidic solution, followed by adjustment to basic (e.g. pH to 8-10) with the addition of a base such as (sodium hydroxide solution). The acidic solution may be a hydrochloric acid or acetic acid solution, preferably having a pH between 0 and 4.
In some embodiments of the invention, in step a1, the solid-to-liquid ratio of the chitin to the acidic solution is 1:5-100.
In some embodiments of the invention, the preparation of chitosan comprises: dissolving chitin in acidic solution (hydrochloric acid, acetic acid) with pH of 0-4, wherein the solid-to-liquid ratio of the chitin to the acidic solution is 1:5-100; adding sodium hydroxide solution (20-60%) into the acidic solution of chitin, and adjusting pH to 8-10 to obtain precipitate 1; carrying out filter pressing, water washing and other steps on the obtained precipitate 1 to obtain a precipitate 2; adding the obtained white precipitate 2 into a reaction kettle, adding a sodium hydroxide solution, and adjusting the pH value to 8-9; then adding hydrogen peroxide solution; adjusting the temperature to 0-95 ℃, and reacting for 0.5-24 hours to obtain a suspension; the suspension is centrifuged, washed with water, centrifuged, etc. to obtain precipitate 3.
In some embodiments of the present invention, the preparation of the chitosan derivative comprises: dissolving chitosan in water, and adjusting pH to 8-10; adding methoxy polyethylene glycol ethylene oxide, adjusting the reaction temperature to 0-95 ℃, and reacting for 0.5-24 hours to obtain transparent liquid; adjusting the pH value of the transparent liquid to 2-4 by using an acid solution, dialyzing (MW-3000 Da), and freeze-drying to obtain a product 1; the molar ratio of the chitosan to the methoxypolyethylene glycol oxirane is 1.1-1;
dissolving amino acid or polypeptide in PBS (0.05M-1M) with pH of 2-6, adding EDC and NHS, activating at 0-4 deg.C for 0.1-4 hr, adding product 1, and reacting at controlled temperature for 0-24 hr; after the reaction is finished and dialyzed (MW-3000 Da), a product 2 is obtained after freeze drying; wherein the molar ratio of the amino group or the polypeptide to EDC and NHS is 1 to 1.5.
In the embodiment of the application, chitin with different molecular weights is prepared through oxidative degradation, and hydroxyethyl is modified on the surface of the chitin, so that the compatibility of the chitin with lipid in the skin stratum corneum is improved; the positive charge quantity of amino acid (such as arginine and histidine) is increased by modifying the amino group, so that the charge content is improved, and the chitosan derivative with adjustable structure and adjustable load quantity is obtained.
According to an embodiment of the invention, water is also included in the composition. The weight ratio of the total weight of chitosan derivative and sodium hyaluronate to water may be (0.01-10): 100.
in a second aspect, the present invention provides a method for preparing a sodium hyaluronate composition as described above, comprising the steps of:
dissolving chitosan derivative in solvent to obtain solution A;
dissolving sodium hyaluronate in a solvent to obtain a solution B;
mixing the solution A and the solution B.
According to an embodiment of the invention, the solvent is water.
According to an embodiment of the invention, the chitosan derivative is present in the solution a in a mass concentration of 0.001% to 50%, such as 0.001%, 0.01%, 0.05%, 0.1%, 0.2%, 0.5%, 1.0%, 2%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45%.
According to an embodiment of the invention, the mass concentration of sodium hyaluronate in solution B is 0.001% to 50%,0.001%, 0.01%, 0.05%, 0.1%, 0.2%, 0.5%, 1.0%, 2%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45%.
According to an embodiment of the invention, the conditions of the mixing comprise: the stirring speed is 10-2000 rpm, and the stirring time is 0.1-48h.
In a third aspect, the present invention also provides a skin care product comprising the sodium hyaluronate composition according to the first aspect of the present invention. The skin care product can be water, milk, cream, etc.
The sodium hyaluronate composition provided by the invention can effectively promote the transdermal absorption of sodium hyaluronate, and has a wide application prospect in the field of skin care products.
Drawings
FIG. 1 is a hydrogen spectrum of the chitosan derivative prepared in example 1.
FIG. 2 is a hydrogen spectrum of hydroxyethyl chitosan prepared in example 1.
FIG. 3 is an IR spectrum of CS, QYJ-CS, JAS-CS, a chitosan derivative, prepared in example 1.
FIG. 4 is a photograph of a fluorescence image of the skin test of an animal using the sample of example 1.
FIG. 5 is a statistical plot of the fluorescence imaging results of FIG. 4.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The specific embodiments described herein are merely illustrative of the invention and do not constitute any limitation on the invention.
Example 1 synthesis of chitosan derivatives: step one, dissolving 10g of chitin in 400ml of 10% hydrochloric acid solution, adjusting the pH value to 3, and stirring for dissolving; 50% NaOH aqueous solution was added thereto, and the pH was adjusted to 8.5 to obtain a white precipitate. Washing the white precipitate, performing pressure filtration, pouring into a three-neck flask, adding 30g of hydrogen peroxide and 170mL of water, adjusting the temperature to 80 ℃, reacting for 6 hours to obtain milky white liquid, and performing centrifugation, water washing and other steps to obtain the white precipitate Chitosan (CS).
And step two, dissolving the white precipitate in 100mL, adjusting the pH value to 9, then adding 0.1g of methoxy PEG ethylene oxide, adjusting the reaction temperature to 60 ℃, reacting for 6 hours, then adjusting the pH value to =4 by using a 10% HCl solution, dialyzing (MW =3000 Da), and freeze-drying to obtain QYJ-CS 8.5g of the product hydroxyethyl chitin.
Step three, 0.712g arginine was dissolved in a buffer solution of pH =4.0 (0.1M), and 0.88g EDC and 0.46g NHS were added in an ice-water bath (0 ℃) and kept for 2h in the ice-water bath.
And adding 4g of the above freeze-dried material hydroxyethyl chitin, reacting at room temperature for 12h, dialyzing (MW =3000 Da), and freeze-drying to obtain the final product chitosan derivative (arginine hydroxyethyl chitin, JAS-CS for short).
FIG. 1 is of JAS-CS of step three 1 HNMR spectrum, FIG. 2 is of QYJ-CS of step two 1 HNMR spectra, FIG. 3 shows Chitosan (CS) in step one, QYJ-CS in step two, and JAS-CS infrared spectra in step three. Example 2:
dissolving 10g of chitin in 400ml of 10% hydrochloric acid solution, adjusting the pH value to 3, and stirring for dissolving; 50% NaOH aqueous solution was added thereto, and the pH was adjusted to 8.5 to obtain a white precipitate. Washing the white precipitate, performing filter pressing, pouring the white precipitate into a three-neck flask, adding 30g of hydrogen peroxide and 170mL of water, adjusting the temperature to 80 ℃, reacting for 6 hours to obtain milky white liquid, and performing centrifugation, water washing and other steps to obtain the white precipitate. The white precipitate was dissolved in 100mL, adjusted to pH 9, then 0.1g methoxy PEG ethylene oxide was added, the reaction temperature was adjusted to 60 ℃, reacted for 6 hours, then adjusted to pH =4 using 10% HCl solution, dialyzed (MW =3000 Da), and freeze dried to give 8.5g product.
Arginine (0.712 g) was dissolved in a buffer solution of pH =4.0 (0.1M), and EDC (0.88 g) and NHS (0.46 g) were added under ice-water bath (0 ℃) and kept for 2h under ice bath. And adding 4g of the freeze-dried product obtained in the previous step, reacting at room temperature for 12h, dialyzing (MW =3000 Da), and freeze-drying to obtain the final product, namely the chitosan derivative. Example 3:
dissolving 15g of chitin in 400ml of 30% acetic acid solution, adjusting the pH value to 1, and stirring for dissolving; adding 20% NaOH aqueous solution, and adjusting pH to 8.5 to obtain white precipitate. Washing the white precipitate, performing pressure filtration, pouring the white precipitate into a three-neck flask, adding 50g of hydrogen peroxide and 250mL of water, adjusting the temperature to 50 ℃, reacting for 8 hours to obtain milky white liquid, and performing centrifugation, water washing and other steps to obtain the white precipitate. The white precipitate was dissolved in 300mL, pH adjusted to 8.5, then 1g methoxy PEG ethylene oxide was added, reaction temperature was adjusted to 45 ℃, reaction was performed for 2 hours, then pH =5.5 was adjusted using 20% HCl solution, and product 12g was obtained after dialysis (MW =3000 Da), freeze drying.
Arginine 0.174g was dissolved in a buffer solution of pH =5.5 (0.1M), and EDC 0.24g and NHS 0.138g were added under ice-water bath (0 ℃), and kept for 2h under ice-bath. And adding 2g of the freeze-dried product obtained in the previous step, reacting at room temperature for 24h, dialyzing (MW =3000 Da), and freeze-drying to obtain the final product, namely the chitosan derivative. Example 4:
5g of the chitosan derivative prepared in example 1 was dissolved in 100mL of water as solution A; 5g of sodium hyaluronate (average molecular weight 130 ten thousand Da) is dissolved in 100mL of water to be used as a solution B; adding the solution B into the solution A at room temperature under the stirring of 200rpm to prepare a chitosan/sodium hyaluronate compound; the obtained compound can be directly used as an effect substance in skin care products after high-temperature sterilization. Example 5:
dissolving 0.5g of chitosan in 100mL of water to obtain solution A; 0.1g of sodium hyaluronate (average molecular weight of 30 ten thousand Da) is dissolved in 100mL of water to be used as a solution B; adding the solution B into the solution A at room temperature under the stirring of 200rpm to prepare a chitosan/sodium hyaluronate compound; the obtained compound can be directly used as an effect substance in skin care products after high-temperature sterilization. Example 6:
dissolving 0.1g of chitosan in 100mL of water to obtain solution A; 0.05g of sodium hyaluronate (average molecular weight 2 ten thousand Da) is dissolved in 100mL of water to be used as a solution B; adding the solution B into the solution A at room temperature under the stirring of 200rpm to prepare a chitosan/sodium hyaluronate compound; the obtained compound can be directly used as an effect substance in skin care products after high-temperature sterilization. Example 7:
0.1g of chitosan/sodium hyaluronate composite prepared in example 5 is dissolved in 5ml of water solution to obtain functionalized sodium hyaluronate.
1. Heating 30g of glycerol, 0.5g of ice crystals, 0.5g of carbomer, 4g of Hojoba wax PEG-120 esters, 4g of PEG-20 methyl glucose sesquistearate, 2g of p-hydroxyacetophenone and 923.9g of deionized water to 85 ℃, and mixing and homogenizing to obtain a mixture;
2. after the temperature is reduced to 45 ℃, adding the functionalized sodium hyaluronate into the solution, and stirring to fully dissolve the functionalized sodium hyaluronate;
adding 10g of 1.2-pentanediol into the solution, fully stirring to obtain essence a, cooling to room temperature, discharging and standing. Example 8:
0.1g of the chitosan derivative/sodium hyaluronate composite prepared in example 5 was dissolved in 5ml of aqueous solution to obtain functionalized sodium hyaluronate.
1. Heating emulsifier CBG 15g, SF1202 40g and caprylic/capric triglyceride 5g to 85 ℃ to prepare a mixture A;
2. putting 1g of bioglycasin, 1g of xanthan gum, 4g of carbomer, 5g of p-hydroxyacetophenone and 5363 g of deionized water 611.5 into a stirring pot, stirring for dissolving while heating to 85-95 ℃ for fully dissolving, and keeping the temperature for 15-20 minutes to obtain a mixture B;
3. adding the mixture A into the mixture B, and stirring for 40min to obtain a mixture C;
4. cooling the mixture C to 40-45 ℃, adding 8g of triethanolamine to prepare 0.5g of functionalized sodium hyaluronate, and stirring for dissolving to prepare a mixture D;
5. adding 10g of 1.2-glycol-free solution into the mixture D at the temperature of 40-45 ℃, fully stirring to obtain emulsion c, cooling to room temperature, discharging and standing.
Application example 1: 1. test sample preparation
5mL of an aqueous solution A containing 1% CSNPs (chitosan derivative prepared in example 1) was prepared.
1g of sodium hyaluronate and sodium hyaluronate (average molecular weight of 30 ten thousand Da) was dissolved in pH5.5 (0.1M PBS), 0.05g of fluorescein was added thereto at room temperature, and after 12 hours of reaction, unreacted fluorescein was removed by a dialysis method (MW =300 Da); obtaining the sodium hyaluronate and sodium hyaluronate marked by fluorescein. And (4) freeze-drying to obtain the finished product of sodium hyaluronate and sodium hyaluronate marked by fluorescein.
And (3) dissolving 0.1g of prepared fluorescein-labeled sodium hyaluronate in 5mL of aqueous solution to obtain a fluorescein-labeled sodium hyaluronate product B.
0.1g of the prepared fluorescein-labeled sodium hyaluronate was dissolved in 5mL of an aqueous solution containing 1% CSNPs (chitosan derivative prepared in example 1), to obtain fluorescein-labeled sodium hyaluronate product C.
0.1g of the prepared fluorescein-labeled sodium hyaluronate was dissolved in 5mL of an aqueous solution containing 1% of CMCS (carboxymethyl chitin) to obtain fluorescein-labeled sodium hyaluronate product D.
0.1g of the prepared fluorescein-labeled sodium hyaluronate was dissolved in 5mL of an aqueous solution containing 1% of HPCS (hydroxypropyl chitin) to obtain fluorescein-labeled sodium hyaluronate product E.
2. Transdermal experiment: 60C 57BL/6 mice were randomly divided into six groups of 10 mice each, i.e., control group, A, B, C, D, E.Each mouse was shaved with 5 x 5cm of hair using an electric razor to expose the skin, and then 0.5mL of the prepared blank solution (ultrapure water, control), A, B, C, D, E, was applied to each of the 2 skin portions thus shaved. After eight hours, after the mice were sacrificed by anesthesia, the skin smeared with the blank solution (ultrapure water, control), a, B, C, D, E was routinely prepared paraffin sections and subjected to fluorescence imaging as shown in fig. 4.
3. The fluorescent quantitative statistical method comprises the following steps: data were analyzed using SPSS13.0 statistical software. The interpretation result comparison of the frozen section direct immunofluorescence staining method adopts x 2 Examination ofWith P<A difference of 0.05 is statistically significant. The results are shown in FIG. 5. In fig. 5, CS represents the absorption amount of the chitosan derivative in a; HA represents the absorption amount of sodium hyaluronate in B; HA @ CSNPs indicates the amount of sodium hyaluronate absorbed in C; HA @ CMCS indicates the amount of sodium hyaluronate absorbed in D; HA @ HPCS indicates the amount of sodium hyaluronate absorbed in E.
4. As a result: as can be derived from fig. 5, the chitosan derivative of the present invention can significantly promote the transdermal absorption of sodium hyaluronate, about 2 times as much as the monomer (sodium hyaluronate alone) at 2 hours; the uptake after 8 hours was about 2.5 times that of the monomer (sodium hyaluronate alone); carboxymethyl chitin and hydroxypropyl chitin do not have the effect of promoting transdermal absorption on sodium hyaluronate.
The technical solution of the present invention is not limited to the limitations of the above specific embodiments, and all technical modifications made according to the technical solution of the present invention fall within the protection scope of the present invention.
Claims (10)
1. A sodium hyaluronate composition comprises chitosan derivative and sodium hyaluronate,
the chitosan derivative includes: (1) a chitosan backbone; (2) a group a linked to the main chain by an ether bond; and (3) a group B attached to the backbone via an amide bond, wherein the group a has one or more hydroxyethyl groups and the group B has one or more acyl groups and one or more amino groups.
2. The sodium hyaluronate composition of claim 1, wherein the chitosan derivative and sodium hyaluronate molecules are present in a weight ratio of 1:0.01-10, and/or the chitosan derivative and the sodium hyaluronate form nanoparticles, and/or the sodium hyaluronate has an average molecular weight of 1000Da-300 ten thousand Da.
3. The composition according to claim 1 or 2, characterized in that the sodium hyaluronate has an average molecular weight of 2-100 ten thousand Da.
4. The sodium hyaluronate composition of claim 1 or 2, wherein the chitosan derivative has at least one of the following structural units 1,2, and 3:
wherein in the structural units 1,2 and 3, A represents the group A, and B represents the group B.
5. The sodium hyaluronate composition according to claim 1 or 2,
the group a is a polyethylene glycol group; and/or
The group a has the following structure:
m is more than or equal to 1; and/or the group B is a group formed by removing one hydroxyl group from an amino acid or polypeptide molecule.
6. The sodium hyaluronate composition of claim 5, wherein the amino acid is selected from one or more of glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, and histidine; and/or the polypeptide is selected from one or more of dipeptide, tripeptide, tetrapeptide, pentapeptide and hexapeptide.
7. The sodium hyaluronate composition of claim 1 or 2, wherein the group B has the following structure:
，
wherein carbonyl C = O is attached to the chitosan backbone; and/or
The group B is
；
And/or the group a has the following structure:
，
m is 1 to 100;
the chitosan derivative has an average molecular weight of 500-18000Da; and/or
The chitosan derivative has an average molecular weight of 537-18000Da.
8. The method of preparing the sodium hyaluronate composition of any one of claims 1 to 7, comprising the steps of:
dissolving chitosan derivative in solvent to obtain solution A;
dissolving sodium hyaluronate in a solvent to obtain a solution B;
mixing the solution A and the solution B.
9. The method according to claim 8,
the solvent is water;
the mass concentration of the chitosan derivative in the solution A is 0.001% -50%;
the mass concentration of the sodium hyaluronate in the solution B is 0.001% -50%;
the mixing conditions include: the stirring speed is 10-2000 rpm, and the stirring time is 0.1-48h.
10. A skin care product comprising the sodium hyaluronate composition of any one of claims 1 to 7.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116574281A (en) * | 2023-05-29 | 2023-08-11 | 中科厚朴(广州)科技发展有限公司 | Hydroxyethyl chitosan-based linked sodium hyaluronate penetration-promoting skin delivery system and preparation and application thereof |
| CN116496429B (en) * | 2023-05-29 | 2024-02-06 | 中科厚朴(广州)科技发展有限公司 | Hydroxyethyl chitosan-based self-assembled transdermal delivery system and preparation and application thereof |
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| CN108175727A (en) * | 2017-12-28 | 2018-06-19 | 广州蜜妆生物科技有限公司 | A kind of anti-acne print Face-protecting mask patch and preparation method thereof |
| CN109984950A (en) * | 2018-12-06 | 2019-07-09 | 上海益好纳米科技有限公司 | A series of disposable hypersorption type nanofiber functional masks and preparation method thereof |
| CN111568792A (en) * | 2020-04-20 | 2020-08-25 | 帅发(厦门)投资有限公司 | Skin-whitening and freckle-removing mask containing coenzyme Q10 and preparation method thereof |
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| DE3632030A1 (en) * | 1986-09-20 | 1988-03-31 | Wella Ag | Thickened cosmetic composition for setting the hairstyle |
| CN108175727A (en) * | 2017-12-28 | 2018-06-19 | 广州蜜妆生物科技有限公司 | A kind of anti-acne print Face-protecting mask patch and preparation method thereof |
| CN109984950A (en) * | 2018-12-06 | 2019-07-09 | 上海益好纳米科技有限公司 | A series of disposable hypersorption type nanofiber functional masks and preparation method thereof |
| CN111568792A (en) * | 2020-04-20 | 2020-08-25 | 帅发(厦门)投资有限公司 | Skin-whitening and freckle-removing mask containing coenzyme Q10 and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116574281A (en) * | 2023-05-29 | 2023-08-11 | 中科厚朴(广州)科技发展有限公司 | Hydroxyethyl chitosan-based linked sodium hyaluronate penetration-promoting skin delivery system and preparation and application thereof |
| CN116496429B (en) * | 2023-05-29 | 2024-02-06 | 中科厚朴(广州)科技发展有限公司 | Hydroxyethyl chitosan-based self-assembled transdermal delivery system and preparation and application thereof |
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| CN115804730B (en) | 2023-04-21 |
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