A xylan tocopherol derivative, its preparation method and application

Abstract

This invention provides a xylan tocopherol derivative, its preparation method, and its application. The structure of the xylan tocopherol derivative is shown in Formula I: where m ≥ 1; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both simultaneously -H; R 12 The xylan-tocopherol derivative has good stability and water solubility, and can exert antioxidant, moisturizing, anti-aging, spot-removing and skin-improving effects, and can be used to make cosmetics and pharmaceuticals.

Description

Technical Field

[0001] This application relates to the fields of pharmaceuticals and cosmetics, specifically to a xylan tocopherol derivative, its preparation method, and its application. Background Technology

[0002] Any discussion of prior art throughout the specification should not be construed as an admission that such prior art is well-known or constitutes part of common general knowledge in the art.

[0003] Tocopherol is a fat-soluble vitamin and one of the body's most important antioxidants. Tocopherol and its derivatives effectively prevent skin oxidative aging and are important active ingredients in cosmetics. However, in simple tocopherol, the hydroxyl groups in its molecular structure are exposed, making it easily oxidized and resulting in poor stability. The prevalence of high-concentration tocopherol cosmetics on the market stems from the fact that tocopherol is easily oxidized and deactivated, necessitating the addition of large quantities to maintain its activity. Tocopherol appears as a golden-yellow or pale-yellow oily liquid and is easily oxidized to a dark red color, affecting its aesthetic appeal as a cosmetic ingredient.

[0004] Heparin-like products possess anti-inflammatory, anti-allergic, and microcirculation-improving bioactive properties, as well as softening, moisturizing, cell-promoting, and wound-healing effects. They benefit skin nutrition and waste excretion, providing excellent skin care and maintenance. Used in products for reducing dark circles and eye bags, they offer repairing, moisturizing, and superior skin feel, suitable for lotions, creams, masks, and serums. Heparin-like substances have similar effects to heparin, improving skin microcirculation, reducing blood viscosity, and promoting blood microcirculation to achieve significant skin-revitalizing and beautifying effects. Xylan polysulfate is a heparin-like substance prepared by chemically sulfonating and then depolymerizing plant-derived macromolecular xylan. It is used as a pharmaceutical for the treatment of interstitial cystitis, arthritis, and other inflammatory conditions.

[0005] Fagus (Geochelone aurea) is widely distributed in Asia, Europe, and North America, and is one of the main constituent tree species of temperate broad-leaved deciduous trees. Trees need to be pruned annually to ensure proper branching and sufficient nutrition. The pruned branches and leaves are generally disposed of through methods such as burning, making organic fertilizer, or using them in mosquito coils, among other low-value processes. Summary of the Invention

[0006] This invention provides a xylan tocopherol derivative, its preparation method, and its applications. The xylan tocopherol derivative of this invention contains both a hydrophobic tocopherol structure and a hydrophilic xylan polysulfate structure, which are covalently linked by ester bonds. This results in excellent stability and water solubility, improving the problem of tocopherol's easy oxidation and color darkening. Furthermore, the xylan tocopherol derivative of this invention also has good moisturizing, antioxidant, anti-aging, spot-removing, and skin-improving effects. In addition, the raw material source for the xylan tocopherol derivative of this invention can be waste branches and leaves from beech pruning. For example, xylan can be extracted from waste branches and leaves of beech pruning, purified, degraded, and sulfonated, and then coupled with tocopherol through ester bonds to obtain the product, achieving high-value recycling of waste branches and leaves.

[0007] Specifically, the present invention provides the following technical solutions.

[0008] In a first aspect of the present invention, a xylan-tocopherol derivative is provided, the structure of which is shown in Formula I: ; Where m≥1; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both of them are -H; R 12 for .

[0009] In some embodiments of the present invention, R 12 The degree of substitution in Formula I is 0.04-1.0; preferably 0.1-0.4.

[0010] In some embodiments of the present invention, the average molecular weight is 1~40kDa; preferably 4kDa-10kDa.

[0011] In a second aspect of the invention, a method for preparing the xylan tocopherol derivative described in the first aspect is provided, comprising: covalently bonding tocopherol with pentosan sulfate to form an ester bond.

[0012] In some embodiments of the present invention, the method includes reacting tocopherol and pentosan sulfate in an alkaline environment. For example, in one embodiment, the method includes: adding pentosan sulfate to a solvent (e.g., dimethylformamide) and stirring until dissolved; adding tocopherol, a condensing agent (e.g., 1-propyl cyclophosphine) and a base (e.g., triethylamine), stirring at 20-30°C, and after the reaction is complete, adding to purified water and then post-processing to obtain the product; in some embodiments, the post-processing procedure includes filtration, washing, and drying, for example, ultrafiltration through a nanofiltration membrane (molecular weight cutoff 500 Da), washing, and lyophilization to obtain the xylan-tocopherol derivative.

[0013] In some embodiments of the present invention, the structure of the pentosan sulfate is shown in Formula II: ; Where m≥1; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both of them are -H; In some embodiments of the present invention, the pentosan sulfate is obtained by sulfation of xylan structures derived from beech pruning branches and leaves.

[0014] In one embodiment, the preparation method of the pentosan sulfate includes: crushing, drying, and pulverizing the pruned branches and leaves of *Fagus stenoptera*; adding the pulverized pruned branches and leaves to an alkaline hydrogen peroxide solution and treating at 85-90°C; filtering the mixture treated with the alkaline solution and collecting the filtrate; cooling the filtrate to room temperature and adjusting the pH to 6-7 with concentrated hydrochloric acid, adding 95% ethanol and allowing it to settle; filtering the precipitated mixture, collecting the filter cake, and recrystallizing the filter cake; drying the recrystallized product in a vacuum drying oven at 50-55°C to obtain xylan; adding the xylan to dimethylformamide, adding chlorosulfonic acid below 10°C, and reacting at 25-30°C; adding the reacted mixture to anhydrous ethanol and allowing it to stand; filtering and collecting the solid; adding the collected solid to purified water, stirring to dissolve, adjusting the pH to 6-7 with 10% NaOH solution; adding to 95% ethanol, allowing it to stand, filtering, and drying to obtain the final product.

[0015] In a third aspect of the invention, a composition is provided comprising the xylan-tocopherol derivative described in the first aspect above.

[0016] In a fourth aspect of the invention, a formulation is provided comprising the xylan-tocopherol derivative described in the first aspect above and at least one excipient.

[0017] Unless otherwise stated, the xylan tocopherol derivatives of this invention are for oral, topical, or injectable use. Those skilled in the art can select appropriate excipients according to conventional methods to prepare the compositions of this invention into suitable dosage forms or usage formats. Such dosage forms include injections, ointments, powder injections, liniments, dressings, liquid formulations, etc. When used as cosmetics, the compositions can include, but are not limited to, toners, lotions, serums, gels, foundations, creams, and masks, etc., and the applications of these cosmetics include, but are not limited to, facial cleansing and care, body cleansing and care, and hair cleansing and care, etc. The xylan tocopherol derivatives of this invention can be used to formulate cosmetics with functions such as sun protection, moisturizing, skin nourishment, anti-inflammation, anti-oxidation, wrinkle reduction, anti-aging, and skin repair.

[0018] In a fifth aspect of the invention, a hydrogel formulation is provided, comprising the xylan-tocopherol derivative, solvent, thickener, viscosity modifier, penetration enhancer, and preservative described in the first aspect above.

[0019] In one embodiment of the present invention, the raw materials of the hydrogel formulation are composed of xylan tocopherol derivative, magnesium chloride (viscosity modifier), xanthan gum (thickener), laurocapram (penetration enhancer), phenoxyethanol (preservative), methylparaben (preservative) and water; wherein the content of the xylan tocopherol derivative in the gel formulation is 200-400 μg / mL.

[0020] In one embodiment of the present invention, the hydrogel formulation may further comprise sodium hyaluronate and glucosamine hydrochloride.

[0021] For example, in one embodiment, the raw material composition of the hydrogel formulation is: 200-400 μg / mL xylan tocopherol derivative, 0.5-1.5% sodium hyaluronate (200~400 kDa), 3.0-9.0% glucosamine hydrochloride, 0.5-1.5% magnesium chloride, 0.5-1.5% xanthan gum, 0.5-1.5% laurocapram, 0.3-0.7% phenoxyethanol, 0.05-0.15% methylparaben, with the balance being water, all of which are mass percentages.

[0022] In a preferred embodiment, the hydrogel formulation comprises the following raw materials: 300 μg / mL xylan tocopherol derivative, 1% sodium hyaluronate (200~400 kDa), 6% glucosamine hydrochloride, 1% magnesium chloride, 1% xanthan gum, 1% laurocapram, 0.5% phenoxyethanol, 0.1% methylparaben, and the balance being water (all by weight percentage).

[0023] In a sixth aspect of the present invention, a method for preparing the hydrogel formulation described in the fifth aspect is provided, comprising: The thickener was added to water and stirred to dissolve, resulting in phase A solution; Xylan tocopherol derivatives, penetration enhancers, preservatives, and stabilizers were added to water and stirred until clear to obtain phase B solution; Phase B was stirred and added to the solution of phase A, stirred until homogeneous, and then cooled to obtain the hydrogel formulation. Preferably, when the hydrogel formulation contains sodium hyaluronate and glucosamine hydrochloride, the method includes: Thickener and hyaluronic acid were added to water and stirred to dissolve, resulting in phase A solution; Xylan tocopherol derivative, glucosamine hydrochloride, penetration enhancer, preservative and stabilizer were added to water and stirred until clear to obtain phase B solution; Phase B was stirred and added to the solution of phase A, stirred until homogeneous, and then cooled to obtain the hydrogel formulation.

[0024] For example, in one specific embodiment, the method for preparing the hydrogel formulation includes: Add 60% of the required amount of water to the reactor, add the thickener and sodium hyaluronate to the required amount of water, heat and stir until fully dissolved to obtain phase A solution; Add xylan tocopherol derivative, penetration enhancer, glucosamine hydrochloride, magnesium chloride and preservative to the remaining water, and stir until the solution is clear to obtain phase B solution; The B-phase solution was slowly added to the A-phase solution while stirring. After stirring until homogeneous, the solution was cooled to obtain a xylan-tocopherol derivative hydrogel.

[0025] In a seventh aspect of the invention, the use of the xylan-tocopherol derivatives described in the first aspect, the compositions described in the third aspect, or the formulations described in the fourth aspect in the preparation of pharmaceuticals or health products with antioxidant activity is provided. In some embodiments of the invention, the antioxidant activity includes, but is not limited to, scavenging reactive oxygen species (ROS).

[0026] In an eighth aspect of the invention, the use of the xylan tocopherol derivative described in the first aspect, the composition described in the third aspect, the formulation described in the fourth aspect, or the hydrogel formulation described in the fifth aspect in the preparation of cosmetic or medical aesthetic products having at least one of the following functions: 1) antioxidation; 2) moisturizing; 3) anti-aging; 4) freckle removal; and 5) skin tone improvement; and in the preparation of food products having at least one of the functions of antioxidation, moisturizing, and freckle removal.

[0027] In some embodiments of the present invention, the antioxidant effect includes, but is not limited to, scavenging reactive oxygen free radicals.

[0028] In some embodiments of the present invention, when the application is for the preparation of cosmetic or medical aesthetic products, the anti-aging includes, but is not limited to, reducing skin wrinkles.

[0029] In some embodiments of the present invention, the freckle removal includes, but is not limited to, reducing the area of ​​freckles.

[0030] In some embodiments of the present invention, when the application is to prepare cosmetic or medical aesthetic products, the improvement of skin tone includes, but is not limited to, whitening, evening out, and brightening of skin tone.

[0031] Compared with existing technologies, the advantages of this invention are: This invention provides a xylan tocopherol derivative derived from beech pruning branches and leaves, its preparation method, and its applications. The xylan tocopherol derivative derived from beech pruning branches and leaves of this invention has excellent moisturizing, hydrating, antioxidant, free radical scavenging, wrinkle-reducing, spot-removing, and skin-improving effects, and also possesses good water solubility and stability, showing promising application prospects. Attached Figure Description

[0032] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments and descriptions of this application are used to explain this application and do not constitute an undue limitation of this application. The embodiments of this application will be described in detail below with reference to the accompanying drawings, wherein: Figure 1 The NMR spectrum of the xylan-tocopherol derivative prepared in Example 1 is shown.

[0033] Figure 2 The figure shows a comparison of the water solubility test results of the xylan tocopherol derivative and tocopherol of the present invention.

[0034] Figure 3 The graph shows the change in the skin moisture growth rate value in Example 4 of the present invention.

[0035] Figure 4 The figure shows a comparison of the reduction in skin wrinkles (%) in Example 4 of the present invention. Detailed Implementation

[0036] The present application is further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer.

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of skill in the art. All reagents and materials used in this application are readily available through conventional means, and unless otherwise specified, they are used in accordance with conventional methods in the art or as per the product instructions. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this application. The preferred embodiments and materials described herein are for illustrative purposes only.

[0038] This invention provides a xylan-tocopherol derivative, the structure of which is shown in Formula I: ; Where m≥1; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both of them are -H; R 12 for (i.e., the tocopherol group).

[0039] In some preferred embodiments, R 12 The degree of substitution in Formula I is 0.04-1.0; preferably 0.1-0.4; the average molecular weight of Formula I is 1-40 kDa; preferably 4 kDa-10 kDa. Xylan tocopherol derivatives within this range have similar and stable properties.

[0040] This invention also provides a method for preparing xylan-tocopherol derivatives of Formula I, comprising: covalently bonding tocopherol with pentosan sulfate to form ester bonds; the reaction route is shown below: .

[0041] Specifically, the preparation and properties of the derivatives described in this invention will be illustrated by the following examples. It should be understood that the examples are for illustrative purposes only and are not exhaustive. Those skilled in the art can easily prepare derivatives with the structure described in this invention or other derivatives with a structure similar to that of this invention based on the present invention, and verify the structure by nuclear magnetic resonance spectroscopy.

[0042] Example 1: Preparation of xylan-tocopherol derivative (Formula I) After pruning, crushing, drying, and further pulverizing the branches and leaves of *Fagus sylvatica*, 4 kg of the powder was added to 20 L of alkaline hydrogen peroxide solution (3% of 30% hydrogen peroxide solution, 10% NaOH) and treated at 85-90℃ for 16 hours. The mixture was then filtered, and the filtrate was collected. The filtrate was cooled to room temperature, and the pH was adjusted to 6-7 with concentrated hydrochloric acid. The solution was then added to 80 L of 95% ethanol and allowed to stand. After sedimentation and filtration, the filter cake was recrystallized and dried in a vacuum drying oven at 50-55℃ to obtain 196 g of xylan. The xylan was added to 10 L of dimethylformamide, and 300 ml of chlorosulfonic acid was added below 10℃. The reaction was carried out at 25-30℃ for 5 hours. The mixture was then added to 40 L of anhydrous ethanol and allowed to stand. After filtration and collection of the solid, it was added to 2 L of purified water, stirred to dissolve, and the pH was adjusted to 6-7 with 10% NaOH solution. The mixture was then added to 8 L of 95% ethanol, allowed to stand, filtered, and dried to obtain 190 g of xylan polysulfate, also known as pentosan sulfate.

[0043] 190.0 g of pentosan sulfate was added to 2 L of dimethylformamide and stirred until dissolved. Then, 430.4 g of tocopherol, 381.6 g of 1-propyl phosphate cycloanhydride (T3P®), and 121.2 g of triethylamine were added. The mixture was stirred at 20–30 °C for 16 hours. After the reaction was complete, the solution was added to 20 L of purified water. The solution was then subjected to ultrafiltration through a nanofiltration membrane (molecular weight cutoff 500 Da), washed, and lyophilized to obtain a xylan-tocopherol derivative with an average molecular weight of 6 kDa and a tocopherol substitution degree of 0.12. Its NMR spectrum is shown below. Figure 1 As shown.

[0044] Example 2 Preparation of xylan-tocopherol derivative (Formula I) After pruning, crushing, drying, and further pulverizing the branches and leaves of *Fagus sylvatica*, 4 kg of the powder was added to 16 L of alkaline hydrogen peroxide solution (2% of 30% hydrogen peroxide solution, 10% NaOH) and treated at 85-90℃ for 16 hours. The mixture was then filtered, and the filtrate was collected. The filtrate was cooled to room temperature, and the pH was adjusted to 6-7 with concentrated hydrochloric acid. The mixture was then added to 64 L of 95% ethanol and allowed to stand, settle, and filter. The filter cake was recrystallized and dried in a vacuum drying oven at 50-55℃ to obtain 209 g of xylan. The xylan was added to 10 L of dimethylformamide, and 300 ml of chlorosulfonic acid was added below 10℃. The reaction was carried out at 25-30℃ for 5 hours. The mixture was then added to 40 L of anhydrous ethanol and allowed to stand. After filtration and collection of the solid, it was added to 2 L of purified water, stirred to dissolve, and the pH was adjusted to 6-7 with 10% NaOH solution. The mixture was then added to 8 L of 95% ethanol, allowed to stand, filtered, and dried to obtain 201 g of xylan polysulfate, also known as pentosan sulfate.

[0045] 200.0 g of pentosan sulfate was added to 2 L of dimethylformamide and stirred until dissolved. 430.4 g of tocopherol, 381.6 g of 1-propyl phosphate cycloanhydride (T3P®), and 121.2 g of triethylamine were added, and the mixture was stirred at 20–30 °C for 16 hours. After the reaction was complete, the solution was added to 20 L of purified water. The solution was then subjected to ultrafiltration through a nanofiltration membrane (molecular weight cutoff 500 Da), washed, and lyophilized to obtain a xylan-tocopherol derivative with an average molecular weight of 9 kDa and a tocopherol substitution degree of 0.11.

[0046] The xylan-tocopherol derivatives of this invention have an average molecular weight of 1-40 kDa, preferably 4-10 kDa, and a degree of substitution of tocopherol in the xylan-tocopherol derivatives of 0.04-1.0, preferably 0.1-0.4. Xylan-tocopherol derivatives within this range exhibit similar and stable properties. Changing the parameters in the preparation process shown in Examples 1 and 2 above can affect the molecular weight and degree of substitution of the product. Obtaining the desired molecular weight and degree of substitution by adjusting the above experimental process is easily achievable by those skilled in the art, and will not be elaborated further in this invention.

[0047] The properties of the xylan tocopherol derivatives of the present invention are further described below.

[0048] Example 3: Stability and Water Solubility Tests 1. Stability test The light and heat stability experiments were conducted on the compound of formula I prepared in Example 1, and compared with tocopherol. The results showed that the compound of formula I had significantly better stability than tocopherol. The experimental methods and results are as follows: Strong light stability test: Tocopherol and the compound of formula I prepared in Example 1 were placed in a test chamber and placed for 4 days under an illuminance of 3000 lx. The decrease in tocopherol content and the decrease in tocopherol content in the compound of formula I prepared in Example 1 were detected by sampling (ultraviolet-visible spectrophotometry). The results are shown in Table 1.

[0049] Table 1

[0050] Thermal stability test: Tocopherol and the compound of formula I prepared in Example 1 were simultaneously placed in a light-protected vacuum drying oven at 40-45°C for 8 days. The decrease in tocopherol content and the decrease in tocopherol content in the compound of formula I prepared in Example 1 were measured by sampling (UV-Vis spectrophotometry), and the results are shown in Table 2. Tocopherol and the compound of formula I prepared in Example 1 were simultaneously placed in a light-protected vacuum drying oven at 70-75°C for 4 days. The decrease in tocopherol content and the decrease in tocopherol content in the compound of formula I prepared in Example 1 were measured by sampling (UV-Vis spectrophotometry), and the results are shown in Table 3.

[0051] Table 2

[0052] Table 3

[0053] Through the above stability tests, the xylan tocopherol derivative of the present invention has higher stability in light and heat environments, and both are far superior to tocopherol.

[0054] 2. Water solubility test Evaluation of solubility: The compounds of formula I prepared in Example 1 were dissolved in purified water at a concentration of 4 mg / ml. Tocopherol was used as a control. It was confirmed that tocopherol is almost insoluble in water at the same concentration and therefore remains opaque, while the compounds of formula I of the present invention are all completely soluble in water (see [link to original text]). Figure 2 It exhibits significantly improved water solubility.

[0055] Example 4 This experiment tested the anti-inflammatory, anti-aging, and wrinkle-reducing effects of the test samples.

[0056] Experimental groups and test samples: The gel mass ratios for each experimental group are as follows: Experimental Group 1: The xylan tocopherol derivative prepared in Example 1 (added at 300 μg / mL), sodium hyaluronate (200~400 kDa) 1%, glucosamine hydrochloride 6%, magnesium chloride 1%, xanthan gum 1%, laurocapram 1%, phenoxyethanol 0.5%, methylparaben 0.1%, and the balance being water.

[0057] Experimental group 2: Tocopherol (300 μg / mL), sodium hyaluronate (200~400 kDa) 1%, glucosamine hydrochloride 6%, magnesium chloride 1%, xanthan gum 1%, laurocapram 1%, phenoxyethanol 0.5%, methylparaben 0.1%, and the remainder was water.

[0058] Experimental group 3: xylan polysulfate (300 μg / mL), sodium hyaluronate (200~400 kDa) 1%, glucosamine hydrochloride 6%, magnesium chloride 1%, xanthan gum 1%, laurocapram 1%, phenoxyethanol 0.5%, methylparaben 0.1%, and the remainder was water.

[0059] Experimental Group 4: A simple mixture of xylan polysulfate and tocopherol (addition amount of 300 μg / mL), sodium hyaluronate (200~400 kDa) 1%, glucosamine hydrochloride 6%, magnesium chloride 1%, xanthan gum 1%, laurocapram 1%, phenoxyethanol 0.5%, methylparaben 0.1%, and the balance being water.

[0060] Blank experimental group 5: Sodium hyaluronate (200~400KDa) 1%, glucosamine hydrochloride 6%, magnesium chloride 1%, xanthan gum 1%, laurocapram 1%, phenoxyethanol 0.5%, methylparaben 0.1%, balance water.

[0061] The method for preparing the gel experimental group can be implemented according to the following steps: (1) Weigh each component according to the above proportion, add 60% of the required amount of water to the reactor, add the thickener (xanthan gum) and sodium hyaluronate to the reactor, stir at 150 r / min and 50°C to fully dissolve, and obtain phase A solution; (2) In another reactor, add 40% of the required amount of water, and add the xylan tocopherol derivative, xylan polysulfate tocopherol, xylan polysulfate, a simple mixture of xylan polysulfate and tocopherol prepared in Example 1, penetration enhancer (lauroquinone), glucosamine hydrochloride, magnesium chloride and preservative (phenoxyethanol and methylparaben), and mechanically stir at 150 r / min until the solution is clear to obtain phase B solution; (3) The B phase solution was slowly added to the A phase solution while stirring. The mixture was stirred at 150 r / min until homogeneous, and then cooled to 20 °C to obtain xylan-tocopherol derivative composite hydrogel.

[0062] 1. Moisturizing effect: 1.1 Subjects: Thirty volunteers aged 25 to 55 years were selected and their facial skin was tested.

[0063] 1.2 Test Samples: The samples from experimental groups 1-5 above (of which experimental group 5 was a blank group) were used as test samples; 1.3 Before the experiment: Subjects were required to wash their faces with clean water. After washing, measurement marks were made on the chin of the subjects' faces. Subjects sat quietly in a constant environment for 30 minutes.

[0064] 1.4 In the experiment: 0.5g of each of the hydrogels in experimental groups 1-5 was evenly applied to the skin of the volunteers' chin. Before the experiment, the blank value of the test site was measured using a Corneometer CM 825 moisture meter to obtain the initial value V0, and then the application of the test product began at the start of the timer. Facial moisture growth rate % = (V t -V0) / V0 Table 1. Changes in Skin Moisture Growth Rate Time Group 10 min 30 min 60 min 120 min 180 min 240 min Experimental group 1 45.7% 44.3% 40.4% 37.2% 33.1% 30.8% Experimental group 2 39.1% 34.1% 30.5% 26.7% 22.4% 20.5% Experimental group 3 38.4% 33.8% 30.1% 26.3% 21.9% 19.7% Experimental group 4 42.5% 41.3% 37.7% 34.5% 30.4% 27.6% Experimental group 5 25.9% 23.4% 20.1% 17.6% 15.8% 13.2% As shown in Table 1, the rate of increase in skin surface moisture gradually decreased over time, with the control group (applying only hyaluronic acid, which has a moisturizing effect) experiencing the fastest moisture loss. The skin treated with the xylan-tocopherol derivative composite hydrogel showed the best moisturizing effect and the slowest decrease in moisture rate, maintaining a strong hydrating effect even after four hours, demonstrating the best results throughout the entire usage period. In contrast, the hydrating effect of gels containing only tocopherol, xylan polysulfate, or a simple mixture of both was significantly lower than that of experimental group 1. This indicates that the superior hydrating effect of this invention is not a result of a simple mixture of tocopherol and xylan polysulfate, but rather due to the special structure of the derivative provided by this invention. The xylan-tocopherol derivative of this invention, through chemical modification, achieves a synergistic hydrating effect of both xylan polysulfate and tocopherol, superior to hyaluronic acid. Furthermore, the flexible structure generated by covalent coupling facilitates skin absorption and deep hydration, thereby extending the product's half-life and achieving long-lasting moisturizing effects.

[0065] 2. Evaluation of wrinkle-reducing efficacy 1.1 Subjects: Thirty volunteers aged 25 to 55 years were selected and their facial skin was tested.

[0066] 1.2 Test Samples: The samples from experimental groups 1-5 above (of which experimental group 5 was a blank group) were used as test samples; 1.3 Before the experiment: The area of ​​facial skin wrinkles S0 of the subjects before the experiment was measured using the Visioline VL 650 wrinkle tester. The changes in the area of ​​facial skin wrinkles were obtained by software analysis.

[0067] 1.4 During the experiment: Volunteers used the test samples according to the instructions. At 2 PM every day (measuring ambient temperature of 20℃ and relative humidity of 50%), the area of ​​facial skin wrinkles (St: changes in the silicone replica film of skin wrinkles) was measured using the Visioline VL 650 wrinkle tester. The changes in the area of ​​facial skin wrinkles were obtained by software analysis.

[0068] Finally, the reduction in skin wrinkle area (%) was calculated as follows: (Skin wrinkle area before the test - Average skin wrinkle area after the test) / Skin wrinkle area before the test × 100%.

[0069] Table 2. Reduction in skin wrinkles (%) Time Group 1 week 2 weeks 3 weeks 4 weeks Experimental group 1 15.4% 16.7% 18.3% 20.4% Experimental group 2 5.2% 6.8% 8.5% 9.6% Experimental group 3 6.0% 7.7% 8.4% 9.2% Experimental group 4 8.7% 10.4% 12.9% 14.3% Experimental group 5 0.1% 0.1% 0.1% 0.1% As shown in Table 2, the area of ​​skin wrinkles in experimental group 5 (blank group) remained almost unchanged, proving that facial wrinkles do not disappear on their own once formed without the application of anti-wrinkle products. The gel in experimental group 1, containing xylan-tocopherol derivatives, showed the most significant anti-wrinkle effect, with its effect continuously increasing over time, significantly higher than gels containing tocopherol, xylan polysulfate, and simple mixtures of the two. This indicates that the xylan-tocopherol derivatives of this invention have a significantly prolonged half-life compared to the active ingredients in other groups, enabling them to better accelerate skin renewal, enhance the skin's physical barrier function, and achieve a better anti-wrinkle effect.

[0070] 3. Evaluation of antioxidant and free radical scavenging (ROS) effects Principle: This invention uses the NBT (nitroblue tetrazolium) photochemical reduction method to determine the antioxidant activity of samples. NBT is reacted with O2... ·- The NBT is reduced to a blue-violet substance, which exhibits maximum absorption in the 530–580 nm range. The NBT reduction reaction may be inhibited in the presence of an antioxidant sample. First, superoxide anions are enzymatically generated via the xanthine-xanthine oxidase system, and then the reduction of NBT at 560 nm is monitored spectrophotometrically.

[0071] Assay method: ① First, prepare 50 μM xanthine in 2 ml of solution in a test tube, and add an appropriate amount of xanthine oxidase to generate 0.024 ΔA min. -1 This is equivalent to 1.1 μMmin -1 O2 ·- Yield.

[0072] ② Accurately weigh 0.0123g NBT, 0.381g methionine (Met), measure 200 μl of 100mmol / L EDTA, and add 0.05 mol / L pH7.8 phosphate buffer to 200ml.

[0073] Add 3 ml of reaction solution ② to reaction solution ①, then add 1 ml of the test solution to the test tube. Irradiate the solution with a 2×40W fluorescent lamp for 20 minutes in a 37℃ water bath, then stop the reaction and place the test tube in darkness. Measure the solution at 25±0.2℃ using a cuvette with a 1cm light path, constant temperature control, and magnetic stirring. Compare its I... 50 Value (i.e., the concentration that produces 50% NBT reduction inhibition).

[0074] Table 3. Evaluation of the effect of scavenging reactive oxygen species (ROS) sample <![CDATA[I 50 Value / μM]]> Experimental group 1 0.2（±0.03） Experimental group 2 1.5（±0.05） Experimental group 3 1.6（±0.04） Experimental group 4 0.7（±0.07） Experimental group 5 2.4（±0.02） Obtain I 50 The smaller the amount of the product, the greater its antioxidant activity. Analysis of the data in Table 3 shows that the I-value of experimental group 1... 50 The value is only 0.2 μM, indicating that it has a strong free radical inhibition effect at low concentrations, showing high activity, and is significantly better than the effects of other experimental groups, especially significantly better than the simple mixture of xylan polysulfate and tocopherol (experimental group 4). This fully proves that the antioxidant effect of the xylan tocopherol derivative prepared in this invention is not produced by the simple mixture of xylan polysulfate and tocopherol, but is due to its structure.

[0075] 4. Evaluation of the effectiveness of the freckle removal treatment Studies have shown that Asians and people with darker skin are more prone to pigmentation. This study selected 30 Chinese female volunteers aged 25-55 with facial melasma and sensitive skin to evaluate the depigmenting effect of xylan-tocopherol derivatives. Pigmentation was assessed by spectrophotometric measurement of gray levels from 0 to 255 (grayscale levels: 0 = black, 255 = white, with increasing values ​​indicating enhanced depigmentation). Analysis of variance and p-value calculation were performed using the Dunnett-t test. The gel from experimental group 1 was applied twice daily to designated areas of the volunteers' faces, with an interval of more than one hour between applications, for eight consecutive weeks. Skin images were acquired using Siascope to identify chromophores such as melanin. Gray levels (color) and surface areas of the designated points and their adjacent normal skin showed that M89PF reduced the area and color of melasma (see Table 4).

[0076] Table 4. Effects of xylan-tocopherol derivative gel on skin color and brown spot surface area.

[0077] Table 4 shows that xylan tocopherol derivatives have significant effects on improving skin tone (brightening), reducing the area of ​​brown spots, and improving the color grade of the surrounding skin, and these effects are enhanced over time.

[0078] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A xylan-tocopherol derivative, the structure of which is shown in Formula I: ； in, m≥1； R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both of them are -H; R 12 for .

2. The xylan-tocopherol derivative according to claim 1, characterized in that, R 12 The degree of substitution in formula I is 0.04-1.

0.

3. The xylan-tocopherol derivative according to claim 1, characterized in that, R 12 The degree of substitution in formula I is 0.1-0.

4.

4. The xylan-tocopherol derivative according to claim 1, characterized in that, Its average molecular weight is 1~40kDa.

5. The xylan-tocopherol derivative according to claim 1, characterized in that, Its average molecular weight is 4kDa-10kDa.

6. A method for preparing the xylan-tocopherol derivative according to any one of claims 1 to 5, comprising: Tocopherol and pentosan sulfate are reacted in an alkaline environment to form covalent bonds to form ester bonds; The structure of the pentosan sulfate is shown in Formula II: ； m≥1; R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 R 11 Each is independently selected from -SO3Na or -H, but not both of them are -H.

7. The method according to claim 6, characterized in that, The pentosan sulfate was obtained by sulfation of xylan structures derived from the pruned branches and leaves of beech.

8. A composition comprising the xylan-tocopherol derivative of any one of claims 1 to 5.

9. A formulation comprising a xylan-tocopherol derivative according to any one of claims 1 to 5 and at least one excipient.

10. A hydrogel formulation comprising the xylan-tocopherol derivative of any one of claims 1 to 5, a solvent, a thickener, a stabilizer, a penetration enhancer, a viscosity modifier, and a preservative.

11. The hydrogel formulation according to claim 10, characterized in that, The raw materials of the hydrogel formulation consist of xylan tocopherol derivatives, magnesium chloride, xanthan gum, laurocapram, phenoxyethanol, methylparaben, and water.

12. The hydrogel formulation according to claim 10, characterized in that, The content of the xylan-tocopherol derivative in the gel formulation is 200-400 μg / mL.

13. The hydrogel formulation according to claim 10, characterized in that, The hydrogel formulation contains sodium hyaluronate and glucosamine hydrochloride.

14. The hydrogel formulation according to claim 13, characterized in that, The molecular weight of the sodium hyaluronate is 200~400 kDa.

15. The hydrogel formulation according to claim 10, characterized in that, The hydrogel formulation comprises the following raw materials: 200-400 μg / mL xylan-tocopherol derivative, 0.5-1.5wt% sodium hyaluronate, 3.0-9.0wt% glucosamine hydrochloride, 0.5-1.5wt% magnesium chloride, 0.5-1.5wt% xanthan gum, 0.5-1.5wt% laurocapram, 0.3-0.7wt% phenoxyethanol, 0.05-0.15wt% methylparaben, with the balance being water.

16. A method for preparing a hydrogel formulation according to any one of claims 10 to 14, comprising: The thickener was added to water and stirred to dissolve, resulting in phase A solution; Xylan tocopherol derivatives, penetration enhancers, preservatives, viscosity modifiers and stabilizers were added to water and stirred until clear to obtain phase B solution; Phase B was stirred and added to the solution of phase A, stirred until homogeneous, and then cooled to obtain the hydrogel formulation.

17. The method according to claim 16, characterized in that, When the hydrogel formulation contains sodium hyaluronate and glucosamine hydrochloride, the method includes: Thickener and hyaluronic acid were added to water and stirred to dissolve, resulting in phase A solution; Xylan tocopherol derivative, glucosamine hydrochloride, penetration enhancer, preservative, viscosity modifier and stabilizer are added to water and stirred until clear to obtain phase B solution; Phase B was stirred and added to the solution of phase A, stirred until homogeneous, and then cooled to obtain the hydrogel formulation.

18. The use of the xylan tocopherol derivative of any one of claims 1 to 5, the composition of claim 8, or the formulation of claim 9 in the preparation of a pharmaceutical or health product having antioxidant activity.

19. The application according to claim 18, characterized in that, The antioxidants include scavenging reactive oxygen free radicals.

20. The use of the xylan tocopherol derivative of any one of claims 1 to 5, the composition of claim 8, the formulation of claim 9, or the hydrogel formulation of any one of claims 10 to 14 in the preparation of cosmetic and medical aesthetic products having at least one of the following functions: 1) anti-oxidation; 2) moisturizing; 3) anti-aging; 4) blemish removal; and 5) skin tone improvement.

21. The use of the xylan tocopherol derivative of claims 1 to 5, the composition of claim 8, the formulation of claim 9, or the hydrogel formulation of any one of claims 10 to 14 in the preparation of a food having at least one of the functions of antioxidation, moisturizing and depigmentation.

22. The application according to claim 20 or 21, characterized in that, The antioxidants include scavenging reactive oxygen free radicals.

23. The application according to claim 20, characterized in that, The anti-aging measures include reducing skin wrinkles.

24. The application according to claim 20 or 21, characterized in that, The removal of freckles includes reducing the area of ​​freckles.

25. The application according to claim 20, characterized in that, The skin tone improvement includes whitening, evening out, and brightening.

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