CN116251037A - Hydrolysis sodium hyaluronate self-assembled structure, and preparation method and application thereof - Google Patents
Hydrolysis sodium hyaluronate self-assembled structure, and preparation method and application thereof Download PDFInfo
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- CN116251037A CN116251037A CN202111502112.3A CN202111502112A CN116251037A CN 116251037 A CN116251037 A CN 116251037A CN 202111502112 A CN202111502112 A CN 202111502112A CN 116251037 A CN116251037 A CN 116251037A
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- sodium hyaluronate
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- 229920002385 Sodium hyaluronate Polymers 0.000 title claims abstract description 190
- 229940010747 sodium hyaluronate Drugs 0.000 title claims abstract description 190
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 title claims abstract description 184
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- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 2
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
- A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18
Abstract
The invention discloses a self-assembled structure containing hydrolyzed sodium hyaluronate, which has an average particle size of 300-2000nm, wherein the polymerization degree of the hydrolyzed sodium hyaluronate is 2-20, and the hydrolyzed sodium hyaluronate can form a self-assembled structure when being dissolved in a polyalcohol aqueous solution, so that the phenomenon that the hydrolyzed sodium hyaluronate is obviously yellowing when being dissolved in water at high temperature can be well relieved. The self-assembled structure of sodium hyaluronate provided by the invention can be applied to various skin care products such as water, cream, essence and the like, so that the problem of yellowing of products caused by yellowing of small molecular sodium hyaluronate is relieved.
Description
Technical Field
The invention belongs to the field of cosmetics, and particularly relates to a self-assembled structure of hydrolyzed sodium hyaluronate, and a preparation method and application thereof.
Background
Sodium Hyaluronate (HA), also known as sodium hyaluronate, is a natural polymeric linear mucopolysaccharide formed by repeatedly connecting D-glucuronic Acid and N-acetylglucosamine as disaccharide units, and is widely used in animal tissues and body fluids, such as joint fluid, vitreous humor, umbilical cord, skin and the like. Sodium hyaluronate has excellent viscoelasticity and excellent water-retaining property due to its unique structure, important physiological function and biological action, excellent histocompatibility and non-immunogenicity, and thus has wide application. At present, the application field of sodium hyaluronate in China is mainly concentrated in the industries of medicine, clinical diagnosis and treatment and cosmetics, and the sodium hyaluronate accounts for more than 98% of the total dosage. In the fields of medicine and clinical diagnosis and treatment, the medicine is widely applied to various ophthalmic operations, such as crystal implantation, cornea transplantation, glaucoma resistant operation and the like, and can also be used for treating arthritis and accelerating wound healing; the product can be used in cosmetics to protect skin, keep skin moist, smooth, fine, tender and elastic, resist wrinkle, care skin, and recover skin physiological function.
Hyaluronic acid and its salt (HA for short) widely exist in nature, are important components of human and animal skin, vitreous body, joint synovial fluid and cartilage tissue, are formed by repeatedly connecting disaccharide units of (1-beta-4) D-glucuronic acid (1-beta-3) N-acetamido glucose, and are chain polyanion macromolecular mucopolysaccharide. Is widely applied to the fields of medical treatment, daily chemicals and food. HA HAs good biocompatibility and few side effects, and research shows that the biological activity of HA HAs obvious M r (relative molecular weight) lazy.
According to the study in the literature, the biological activity of sodium hyaluronate is related to the size of molecular weight, and the smaller the molecular weight is, the smaller the polymerization degree is, and the higher the biological activity is. In the cosmetic field, it is common to apply sodium hyaluronate with different molecular weights to cosmetics with different effects. The macromolecular hyaluronic acid can form a layer of breathable film on the surface of skin to make the skin smooth and moist, and can prevent invasion of foreign bacteria, dust and ultraviolet rays and protect the skin from invasion; the medium molecular hyaluronic acid can tighten skin and keep moisture for a long time; the small molecular hyaluronic acid can penetrate into dermis, has the effects of slightly dilating capillary vessels, increasing blood circulation, improving intermediate metabolism, promoting skin nutrition absorption, and has strong wrinkle eliminating function, and can increase skin elasticity and delay skin aging.
Disclosure of Invention
Small molecule hyaluronic acid, such as sodium hyaluronate with repeating units of 2-20, is sensitive to temperature and is easy to yellow in high temperature environment, so that the operation temperature and storage condition of the small molecule hyaluronic acid are limited greatly. In the practical application process, the application of the small-molecule hyaluronic acid is limited, and the full play of the characteristics of the small-molecule hyaluronic acid is not facilitated, so that the expected use effect is achieved.
In view of the above, the invention provides a self-assembled structure containing hydrolyzed sodium hyaluronate, which can relieve yellowing of small molecular sodium hyaluronate, improve the activity exertion of the small molecular sodium hyaluronate and widen the use scene of the small molecular sodium hyaluronate.
Specifically, the invention adopts the following technical scheme
1. A self-assembled structure comprising hydrolyzed sodium hyaluronate, wherein the average particle size is 300 to 2000nm.
2. The self-assembled structure according to item 1, wherein the degree of polymerization of the hydrolyzed sodium hyaluronate in the self-assembled structure is 2 to 20.
3. The self-assembled structure according to item 1 or 2, wherein the self-assembled structure is formed by dispersing sodium hyaluronate hydrolyzed in an aqueous solution of a polyhydric alcohol,
preferably, the mass ratio of the sodium hyaluronate to the polyol is 1:1-1:30, and more preferably, the mass ratio of the sodium hyaluronate to the polyol is 1:5-1:20.
4. The self-assembled construction according to claim 3, wherein the polyol is selected from one or more of butanediol, pentanediol, and propanediol, preferably one or more of butanediol and pentanediol,
further preferably, the polyol is a combination of two of pentanediol and butanediol, and the mass ratio of butanediol to pentanediol is 1:10-10:1, and further preferably, the mass ratio is 1:5-3:1.
5. The self-assembled structure according to any one of claims 1 to 4, wherein the self-assembled structure consists of hydrolyzed sodium hyaluronate.
6. The self-assembled structure according to any one of claims 1 to 5, further comprising sodium hyaluronate, preferably having a molecular weight of 20 to 100kDa, more preferably having a molecular weight of 20 to 50kDa.
7. The self-assembled structure according to item 6, wherein the mass ratio of hydrolyzed sodium hyaluronate to acetylated sodium hyaluronate is 1:4 to 10:1, preferably 1:2 to 10:1.
8. The self-assembled structure according to item 6 or 7, characterized in that it consists of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate.
9. A method for preparing a hydrolyzed sodium hyaluronate self-assembled structure, comprising the steps of:
weighing sodium hyaluronate and polyalcohol according to the mass ratio or weighing sodium hyaluronate, polyalcohol and sodium hyaluronate according to the mass ratio;
dissolving sodium hyaluronate and polyalcohol in water to form a mixed solution or dissolving sodium hyaluronate in water to form phase A, mixing sodium hyaluronate with dihydric alcohol to form phase B, and mixing phase A and phase B to form a mixed solution;
stirring the mixed solution until the mixed solution is completely dissolved;
standing and cooling the completely dissolved solution;
preferably, the mixed solution is heated before being stirred, and more preferably, the heating temperature is 30 to 60 ℃ and the holding time is 25 to 50 minutes.
10. The small molecule sodium hyaluronate self-assembled structure prepared according to the method of item 9 is the self-assembled structure of any one of items 1 to 8.
11. The self-assembled structure according to any one of items 1 to 8 or the self-assembled structure prepared by the method according to any one of items 9 to 10, for use in alleviating yellowing of small molecule sodium hyaluronate.
12. The self-assembled construction according to any one of items 1 to 8 or the self-assembled construction prepared by the method according to any one of items 9 to 10, for use in skin care products,
preferably, the skin care product is water, cream, ointment, or cream.
13. A skin care product comprising the self-assembled structure according to any one of claims 1 to 8.
Effects of the invention
1. The self-assembled structure of sodium hyaluronate provided by the invention can effectively relieve the phenomenon that the small molecular sodium hyaluronate is high Wen Bianhuang in aqueous solution.
2. According to the invention, through reasonable compounding of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate, a sodium hyaluronate self-assembly structure is further formed, and the particle size of the self-assembly structure can be reduced, so that the yellowing problem of small molecular sodium hyaluronate is better relieved.
3. The self-assembled structure of sodium hyaluronate provided by the invention can be applied to skin care products such as water, cream and the like, and can be used for relieving the problem of yellowing of products caused by small-molecule sodium hyaluronate.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art. Wherein:
FIG. 1 is a nanostructure formed by self-assembly of hydrolyzed sodium hyaluronate;
FIG. 2 shows the self-assembled nano-structure of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate.
Detailed Description
The following description of the embodiments of the present invention will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the invention are shown. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that certain terms are used throughout the description and claims to refer to particular components. Those of skill in the art will understand that a person may refer to the same component by different names. The specification and claims do not identify differences in terms of components, but rather differences in terms of the functionality of the components. As referred to throughout the specification and claims, the terms "include" or "comprising" are used in an open-ended fashion, and thus should be interpreted to mean "include, but not limited to. The description hereinafter sets forth a preferred embodiment for practicing the invention, but is not intended to limit the scope of the invention, as the description proceeds with reference to the general principles of the description. The scope of the invention is defined by the appended claims.
The invention provides a self-assembled structure containing hydrolyzed sodium hyaluronate.
The average grain diameter of the self-assembled structure provided by the invention is 300-2000nm.
The average particle diameter as used herein means a D50 particle diameter, and the D50 particle diameter is a particle diameter (particle diameter) corresponding to a cumulative particle size distribution percentage of a sample of 50%, and is also referred to as a median diameter or median particle diameter. The method of measuring the average particle diameter D50 of the present invention includes, but is not limited to, measurement using a measuring instrument such as a particle size analyzer, dynamic laser light scattering instrument, laser particle size analyzer, and the like.
In one embodiment of the present invention, the average particle size described herein is measured using a NanoBrook 90Plus PALS dynamic laser light scattering instrument.
The self-assembled structures of the invention have an average particle size of 300-2000nm, for example 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, 1000nm, 1100nm, 1200nm, 1300nm, 1400nm, 1500nm, 1600nm, 1700nm, 1800nm, 1900nm, 2000nm.
The hydrolyzed sodium hyaluronate is high-activity ultra-small molecular sodium hyaluronate, has higher transdermal absorptivity than common macromolecular sodium hyaluronate, is more deeply moisturized, improves the moisture content of skin, and can repair damaged skin and improve the activity of cells so as to reduce the damage of the environment to skin cells. The polymerization degree of the hydrolyzed sodium hyaluronate refers to the number of disaccharide units consisting of glucuronic acid and N-acetamido glucose in sodium hyaluronate molecules, the molecular weight range of the hydrolyzed sodium hyaluronate can be measured by using an Ubbelohde viscometer to measure the relative viscosity, and the average molecular weight is calculated according to a formula.
The self-assembled structure refers to an ordered structure formed spontaneously by basic structural units (molecules, nanomaterials, substances of micrometer or larger scale). During self-assembly, the basic building blocks spontaneously organize or aggregate into a stable, regular geometric appearance under non-covalent based interactions. The structure and number of self-assembled components and the solvent have an effect on the structure of the self-assembled aggregates.
In the self-assembled structure of the hydrolyzed sodium hyaluronate, the polymerization degree of the hydrolyzed sodium hyaluronate is 2 to 20.
The degree of polymerization is a measure of the molecular size of the polymer. The average value of the number of repeating units contained in the polymer macromolecular chain is represented by n based on the number of repeating units.
The degree of polymerization of the hydrolyzed sodium hyaluronate as described above may be 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20.
Further, the self-assembled structure of the hydrolyzed sodium hyaluronate is formed by dissolving in an aqueous solution of a polyhydric alcohol.
Further, the mass ratio of the hydrolyzed sodium hyaluronate to the polyol is 1:1-1:30, for example, the mass ratio may be 1:2-1:29, 1:3-1:28, 1:3-1:27, 1:4-1:26, 1:4-1:25, 1:5-1:24, 1:5-1:23, 1:5-1:22, 1:5-1:21, 1:5-1:20, 1:6-1:20, 1:7-1:18, 1:8-1:17, etc.
Preferably, the ratio of the hydrolyzed sodium hyaluronate to the polyol is 1:5-1:20.
Further, in the self-assembled structure of the hydrolyzed sodium hyaluronate, the polyhydric alcohol is selected from any one or a combination of several of propanol, isopropanol, propylene glycol, 1, 3-propylene glycol, dipropylene glycol, glycerin, diglycerin, butylene glycol, 1, 3-butylene glycol, 1, 2-butylene glycol, 1, 4-butylene glycol, 2, 3-butylene glycol, pentylene glycol, 1, 2-pentylene glycol, 1, 5-pentylene glycol, t-butanol, diethylene glycol, triethylene glycol, hexanol, 1, 2-hexylene glycol, 1, 6-hexylene glycol, nonylene glycol, 1, 9-nonylene glycol, lactitol, octanediol, and ethylene glycol.
In some embodiments, the polyol is one or more of butanediol, pentanediol, and propanediol,
preferably, the polyol is butanediol, pentanediol or propylene glycol;
preferably, the polyol is pentanediol or propylene glycol;
preferably, the polyol is butanediol or propylene glycol;
preferably, the polyol is butanediol or pentanediol;
preferably, the polyol is butanediol;
preferably, the polyol is pentanediol.
In the self-assembled structure of the hydrolyzed sodium hyaluronate, when the polyhydric alcohol is a combination of two of pentanediol and butanediol, the mass ratio of butanediol to pentanediol is 1:10-10:1, for example, the mass ratio can be 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1.
Preferably, the mass ratio of the butanediol to the pentanediol is 1:5-3:1.
In certain embodiments of the invention, the self-assembled structure consists of hydrolyzed sodium hyaluronate. That is, only one component of sodium hyaluronate is hydrolyzed in the self-assembled structure.
Furthermore, the self-assembled structure of the hydrolyzed sodium hyaluronate provided by the invention also comprises acetylated sodium hyaluronate.
The sodium hyaluronate is obtained by acetylation reaction of sodium hyaluronate, and the introduction of acetyl makes the sodium hyaluronate have hydrophilicity and lipophilicity, can play roles in double moisturizing, repairing stratum corneum barrier, improving bioactivity such as skin elasticity and the like, and simultaneously makes the sodium hyaluronate have targeting property due to the lipophilic property. The molecular weight range of the sodium hyaluronate can be obtained by measuring the relative viscosity by using an Ubbelohde viscometer and calculating according to a formula.
Further, the molecular weight of the acetylated sodium hyaluronate in the hydrolyzed sodium hyaluronate self-assembled structure as described above may be in the range of 20 to 100kDa, for example, the molecular weight may be 20 to 99kDa, 20 to 98kDa, 20 to 95kDa, 20 to 90kDa, 20 to 88kDa, 20 to 85kDa, 20 to 83kDa, 20 to 80kDa, 20 to 78kDa, 20 to 76kDa, 20 to 70kDa, 20 to 65kDa, 20 to 60kDa, 20 to 55kDa, 20 to 50kDa, 20 to 40kDa, 20 to 30kDa.
Preferably, the molecular weight of the acetylated sodium hyaluronate is 20-50 kDa.
Further, in the hydrolyzed sodium hyaluronate self-assembled structure as described above, the mass ratio of the hydrolyzed sodium hyaluronate to the acetylated sodium hyaluronate is 1:4 to 10:1, for example, the mass ratio may be 1:4, 1:3, 1:2, 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1.
Preferably, the mass ratio of the hydrolyzed sodium hyaluronate to the acetylated sodium hyaluronate is 1:2-10:1.
In certain embodiments of the invention, the self-assembled structure consists of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate. Namely, the self-assembled structure has only two components of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate.
The invention further provides a method for preparing the self-assembled structure of the hydrolyzed sodium hyaluronate, which is characterized by comprising the following steps of:
weighing sodium hyaluronate and polyalcohol according to the mass ratio or weighing sodium hyaluronate, polyalcohol and sodium hyaluronate according to the mass ratio;
dissolving sodium hyaluronate and polyalcohol in water to form a mixed solution or dissolving sodium hyaluronate in water to form phase A, mixing sodium hyaluronate with dihydric alcohol to form phase B, and mixing phase A and phase B to form a mixed solution;
stirring the mixed solution until the mixed solution is completely dissolved;
standing and cooling the completely dissolved solution;
preferably, the mixed solution is heated before being stirred, and the heating temperature may be 30 to 60 ℃, for example, 30 ℃, 32 ℃, 35 ℃, 38 ℃, 40 ℃, 43 ℃,45 ℃, 48 ℃, 50 ℃, 55 ℃, 60 ℃. The heating time is kept between 25 and 50 minutes.
Preferably, the heating temperature is 45 ℃ and the holding time is 30 minutes.
Further, the self-assembled structure of sodium hyaluronate prepared by any one of the preparation methods is any one of the self-assembled structures of sodium hyaluronate provided by the invention as described above.
Furthermore, the invention provides application of any of the hydrolyzed sodium hyaluronate self-assembled structures in relieving yellowing of small molecule sodium hyaluronate. Including but not limited to, yellowing due to improper storage, yellowing due to temperature changes, yellowing due to excessive time, and yellowing due to other factors.
Further, the invention provides the use of any of the hydrolyzed sodium hyaluronate self-assembled structures described above in a skin care product.
Such applications include, but are not limited to, the addition of the hydrolyzed sodium hyaluronate self-assembled structures provided herein to skin care products, use in direct combination with skin care products, use in indirect combination with other skin care products.
The skin care products include, but are not limited to, water, creams, ointments, creams, essences, sunscreens, oils, body-refreshing, bathing, periocular skin care, facial masks, facial washes, cleansing, foundations, foundation pads, rouges, body-applied make-up, eyebrows, eye shadows, eyelids, eye hair, eye makeup removers, lip balms, lip gloss oils, general lip balms, lip pencil.
Further, the skin care product is a product in the forms of water, cream, ointment, cream and the like.
The invention further provides a skin care product comprising any of the hydrolyzed sodium hyaluronate self-assembled structures as described above.
The beneficial effects are that:
1. compared with sodium hyaluronate dissolved in the solution, the self-assembled structure of the hydrolyzed sodium hyaluronate provided by the invention has stronger thermal stability because the self-assembled structure is a supermolecule aggregate in the solution, and effectively relieves the yellowing phenomenon of small molecule sodium hyaluronate caused by the rise of temperature in the aqueous solution.
2. The invention further provides a hydrolyzed sodium hyaluronate self-assembled structure prepared by reasonably compounding hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate, wherein the acetylated sodium hyaluronate has certain lipophilic capacity while having hydrophilicity, so that the amphipathy of a system can be enhanced, the formed hydrolyzed sodium hyaluronate self-assembled structure has a denser nanoparticle structure, the particle size of particles is smaller, the hyaluronic acid units are more fully wrapped, and the sodium hyaluronate is prevented from being oxidized and yellowing at high temperature, so that the problem of yellowing of micromolecular sodium hyaluronate is better relieved.
3. The hydrolyzed sodium hyaluronate self-assembled structure provided by the invention can be applied to various skin care products such as water, cream, ointment, cream, essence and the like, so that the problem of yellowing of products caused by yellowing of small molecular sodium hyaluronate is relieved.
Examples
The following description of the embodiments of the present invention will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the invention are shown. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified. Wherein the sodium hyaluronate used has a polymerization degree of 10-15, and is obtained from Kaschin Biotech Co., ltd (trade name: ximen repair) TM Super-active hyaluronic acid, lot number: 19122443 Sodium hyaluronate having a molecular weight of 20-30kDa, purchased from the china-xi biotechnology company (trade name: hymagic TM AcHA, lot number: 20081322 A) is provided; the butanediol used was 1, 3-butanediol and the pentanediol used was 1, 2-pentanediol.
Table 1 component tables of examples and comparative examples
Comparative example 1
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding water to 100g, maintaining at 45deg.C for 30min, and stirring to dissolve completely.
Comparative example 2
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, 0.17g of acetylated sodium hyaluronate, adding 99.33g of water, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 1
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 8.0g of butanediol, dispersing uniformly to obtain phase B, slowly adding phase A into phase B, maintaining at 45deg.C for 30min, and stirring to dissolve completely.
Example 2
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 8.0g of pentanediol, dispersing uniformly to obtain phase B, slowly adding phase A into phase B, maintaining at 45deg.C for 30min, and stirring to dissolve completely.
Example 3
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 7.0g of butanediol and 1.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 4
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 5
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 4.0g of butanediol and 4.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 6
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 1.0g of butanediol and 6.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 7
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 98.2g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 0.5g of butanediol and 0.3g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 8
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 97.4g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 1.0g of butanediol and 0.6g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 9
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 89g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 6.25g of butanediol and 3.75g of pentanediol, dispersing uniformly to obtain phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 10
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 92.6g of water to dissolve into phase A, adding 0.5g of acetylated sodium hyaluronate, adding 4g of butanediol and 2.4g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 11
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 86.5g of water to dissolve into phase A, adding 5.0g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 12
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 89.5g of water to dissolve into phase A, adding 2.0g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until the phase A is completely dissolved.
Example 13
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 90.5g of water to dissolve into phase A, adding 1.0g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 14
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.5g of water to dissolve into phase A, 5.0g of butanediol and 3.0g of pentanediol, mixing uniformly to obtain phase B, slowly adding phase A into phase B, maintaining at 45deg.C for 30min, and stirring to dissolve completely.
Example 15
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.25g of water to dissolve into phase A, adding 0.25g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 16
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.33g of water to dissolve into phase A, adding 0.17g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 17
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.365g of water to dissolve into phase A, adding 0.125g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 18
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.4g of water to dissolve into phase A, adding 0.1g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 19
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.45g of water to dissolve into phase A, adding 0.05g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Example 20
Precisely weighing 0.5g of hydrolyzed sodium hyaluronate, adding 91.48g of water to dissolve into phase A, adding 0.02g of acetylated sodium hyaluronate, adding 5.0g of butanediol and 3.0g of pentanediol, dispersing uniformly to form phase B, slowly adding phase A into phase B, maintaining at 45 ℃ for 30min, and stirring until completely dissolving.
Test examples
1. Color change measurement
The prepared samples are respectively placed in a room temperature and 55 ℃ oven, taken out after 10 days, and the samples stored at 55 ℃ are compared with the samples stored at room temperature to observe the color change. And each sample was tested 3 times at 435nm wavelength using an ultraviolet spectrophotometer, and the average was taken, the greater the absorbance at this wavelength, the more pronounced the color yellowing, and the test results are shown in table 2.
Degree of color change= (a 435 -55℃-A 435 -RT)*1000
Table 2 color change degree table of examples and comparative examples
As can be seen from the data in the table, the color of each example and the sample of the comparative example did not change significantly after ten days at room temperature, but the color of each example began to be darkened to yellow to a different extent after ten days at a high temperature of 55 ℃, wherein the sodium hyaluronate hydrolysate alone of comparative example 1 was dissolved in water and the yellowing was more significant after standing at high temperature, and the sodium hyaluronate hydrolysate and sodium hyaluronate hydrolysate of comparative example 2 were simultaneously dissolved in water and the yellowing of the solution formed by the self-assembled structures of sodium hyaluronate hydrolyzed according to the present invention was also more significant, and the yellowing of the solution formed by the self-assembled structures of sodium hyaluronate hydrolyzed according to the present invention had very significant alleviation effect relative to the yellowing of the sodium hyaluronate hydrolysate alone, particularly, examples 4, 5, 9, 13, 15, 16, 17, 18, 19, which showed little difference in color after storing at room temperature and at a high temperature of 55 ℃.
2. Particle size characterization
The average particle size and particle size distribution of the samples of the above comparative examples and examples were measured 3 times for each sample particle size using a NanoBrook 90Plus PALS dynamic laser light scattering instrument, and the average was taken. The test results are shown in Table 3.
According to the data in the table, the independent hydrolyzed sodium hyaluronate is dissolved in water at room temperature and high temperature of 55 ℃ to form no self-assembled structure, the particle size can not be measured, the self-assembled structure of the hydrolyzed sodium hyaluronate provided by the invention can be observed under a dynamic laser light scattering instrument, and according to the measurement, at room temperature, the self-assembled structure of different particle sizes is formed in the sample of the embodiment of the invention, the particle size of the self-assembled structure in the sample of each embodiment does not become particularly obvious at high temperature of 55 ℃, so that the self-assembled structure provided by the invention is very stable at high temperature and is not easy to damage, and from the particle size distribution of the embodiment, the smaller the particle size of the embodiment sample is, the less obvious the color yellowing is, namely the better relieving effect on the color yellowing at high temperature is provided.
Table 3 particle size change table for each of examples and comparative examples
3. Microstructure characterization
The morphology of the samples obtained in example 14 and example 15 was characterized by using Hitachi S-4800FE-SEM, and the samples were added dropwise to a silicon wafer in an appropriate amount, dried in the air, subjected to a metal spraying treatment, and then observed in morphology as shown in FIG. 1 and FIG. 2. As can be seen from fig. 1, under the preparation conditions of the present invention, hydrolyzed sodium hyaluronate forms a self-assembled structure in a polyol solution, unlike sodium hyaluronate solution which is completely dissolved in water. In fig. 2, it can be seen that the self-assembled structure formed by the hydrolyzed sodium hyaluronate and the acetylated sodium hyaluronate has a smaller and denser particle size, and the hyaluronic acid units are more fully wrapped, so that the hyaluronic acid units are prevented from being oxidized and yellowing at high temperature.
4. Use in skin care products
The hyaluronic acid composition can be applied to skin care products, and can alleviate the yellowing phenomenon of small molecular HA while exerting skin care effect, for example, 98.5g of the composition containing self-assembled structure obtained in example 15 is taken, 0.5g of the active ingredients of ectoin, 0.2g of trehalose, 0.2g of allantoin and 0.3g of xanthan gum are added to prepare essence, and the essence still HAs no obvious yellowing phenomenon after being placed at a high temperature of 55 ℃ for 10 days, and table 4 is an essence formula containing the sodium hyaluronate composition.
Table 4 essential liquid composition table
| Sequence number | Composition of the components | Quality of |
| 1 | The composition obtained in example 15 | 98.5g |
| 2 | Ikeduoyin | 0.5g |
| 3 | Trehalose | 0.2g |
| 4 | Allantoin | 0.2g |
| 5 | Xanthan gum | 0.3g |
Claims (13)
1. A self-assembled structure comprising hydrolyzed sodium hyaluronate, wherein the average particle size is 300 to 2000nm.
2. The self-assembled structure according to claim 1, wherein the degree of polymerization of the hydrolyzed sodium hyaluronate in the self-assembled structure is 2 to 20.
3. The self-assembled structure according to claim 1 or 2, wherein the self-assembled structure is formed by dispersing sodium hyaluronate hydrolyzed in an aqueous solution of a polyhydric alcohol,
preferably, the mass ratio of the sodium hyaluronate to the polyol is 1:1-1:30, and more preferably, the mass ratio of the sodium hyaluronate to the polyol is 1:5-1:20.
4. A self-assembled construction according to claim 3, wherein the polyol is selected from one or more of butanediol, pentanediol, and propanediol, preferably one or more of butanediol and pentanediol,
further preferably, the polyol is a combination of two of pentanediol and butanediol, and the mass ratio of butanediol to pentanediol is 1:10-10:1, and further preferably, the mass ratio is 1:5-3:1.
5. The self-assembled structure according to any one of claims 1 to 4, characterized in that it consists of hydrolyzed sodium hyaluronate.
6. The self-assembled structure according to any one of claims 1 to 5, further comprising sodium hyaluronate, preferably having a molecular weight of 20 to 100kDa, more preferably having a molecular weight of 20 to 50kDa.
7. The self-assembled structure according to claim 6, wherein the mass ratio of hydrolyzed sodium hyaluronate to acetylated sodium hyaluronate is 1:4 to 10:1, preferably 1:2 to 10:1.
8. The self-assembled structure according to claim 6 or 7, characterized in that it consists of hydrolyzed sodium hyaluronate and acetylated sodium hyaluronate.
9. A method for preparing a hydrolyzed sodium hyaluronate self-assembled structure, comprising the steps of:
weighing sodium hyaluronate and polyalcohol according to the mass ratio or weighing sodium hyaluronate, polyalcohol and sodium hyaluronate according to the mass ratio;
dissolving sodium hyaluronate and polyalcohol in water to form a mixed solution or dissolving sodium hyaluronate in water to form phase A, mixing sodium hyaluronate with dihydric alcohol to form phase B, and mixing phase A and phase B to form a mixed solution;
stirring the mixed solution until the mixed solution is completely dissolved;
standing and cooling the completely dissolved solution;
preferably, the mixed solution is heated before being stirred, and more preferably, the heating temperature is 30 to 60 ℃ and the holding time is 25 to 50 minutes.
10. The small molecule sodium hyaluronate self-assembled structure prepared according to the method of claim 9 is the self-assembled structure of any one of claims 1 to 8.
11. Use of a self-assembled structure according to any one of claims 1 to 8 or a self-assembled structure prepared by a method according to any one of claims 9 to 10 for alleviating yellowing of small molecule sodium hyaluronate.
12. The use of a self-assembled structure according to any one of claims 1 to 8 or a self-assembled structure prepared by a method according to any one of claims 9 to 10 in a skin care product,
preferably, the skin care product is water, cream, ointment, or cream.
13. A skin care product comprising the self-assembled structure of any one of claims 1 to 8.
Priority Applications (1)
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