Photocrosslinkable polymer with anti-uv efficacy, method for its preparation and use

Abstract

The present application relates to a kind of photo-crosslinkable polymer with anti-UV effect, its preparation method and application, with the anti-UV effect of small molecule compound is connected to the hydrophilic natural polymer skeleton by chemical bond connection mode, while introducing photo-crosslinkable (methyl) acryl, prepare the photo-crosslinkable polymer with anti-UV effect, its solution is irradiated after specific wavelength light, under the action of photoinitiator, (methyl) acryl is initiated crosslinking polymerization, form the water gel that does not flow, form physical barrier in contact site, block external ultraviolet radiation or pollution.Anti-UV small molecule is connected by chemical bond in crosslinking network, play out sunscreen effect, while, the mechanical strength of gel network can resist water impact and the penetration of sweat, so that the sunscreen water gel of the present application is in extension sunscreen molecule's retention time, also reduce the security risk of small molecule sunscreen agent penetration into skin.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of cosmetics, and particularly relates to a photo-crosslinkable polymer with anti-ultraviolet effect, a preparation method thereof and application. BACKGROUND

[0002] Ultraviolet (UV) is divided into UVA (320-400nm), UVB (280-320nm), and UVC (100-280nm) according to wavelength, wherein UVC is basically blocked by the ozone layer, and UVA and UVB can reach the ground. Short-term exposure to these lights can cause skin erythema, edema, pigment deposition, etc., and long-term exposure can cause skin photoaging, skin cancer, pigment abnormalities, eye damage, etc. Therefore, it is particularly important to develop ultraviolet protection products.

[0003] Sunscreen is a protective cosmetic applied to the surface of the human body, and is the last barrier against ultraviolet rays. Sunscreen mainly relies on various sunscreen agents to work, and sunscreen agents can be divided into physical sunscreen agents and chemical sunscreen agents. Physical sunscreen agents (such as zinc oxide and titanium dioxide) achieve sunscreen effect by reflecting ultraviolet rays, while chemical sunscreen agents are a class of organic compounds that absorb ultraviolet rays and convert them into heat energy for release, used to protect the skin from UVA and UVB damage. Unlike physical sunscreens, chemical sunscreens are lighter and easier to apply, making them more suitable for daily use.

[0004] However, current chemical sunscreens can cause photodegradation, skin penetration, and other phenomena, which can cause potential biological toxicity, endocrine disruption, and other safety issues. In addition, sunscreen stays on the surface of the human skin through physical application, and there is a problem of loss when exposed to water or sweat, resulting in a loss of resistance to ultraviolet rays. Therefore, it is particularly necessary to develop long-acting, water-resistant, and sweat-resistant ultraviolet protection products. SUMMARY

[0005] In view of the technical problems existing in the prior art, the present application provides a photo-crosslinkable polymer with anti-ultraviolet effect, a preparation method thereof and application, aiming to achieve long-acting, water-resistant, and sweat-resistant ultraviolet protection function.

[0006] In a first aspect of the present application, a photo-crosslinkable polymer with anti-ultraviolet effect is provided, having a structure as shown in formula I:

[0007]

[0008] The curve in formula I is a natural polymer backbone selected from any one of hyaluronic acid, alginic acid, gelatin, collagen, chitosan, cellulose and chondroitin sulfate; R is any one of hydroxyl, carboxyl, amino, R1 is a decarboxylation residue of a small molecule sunscreen agent containing a carboxyl structure; R2 is (meth) acryloyl; X, Y are each independently selected from an ester bond, an amide bond, a coupling agent linked by an ester bond or an amide bond at both ends.

[0009] In some embodiments of the present application, the coupling agent is selected from any one of ethylenediamine, propylenediamine, butylenediamine, pentanediamine, hexanediamine, heptanediamine, octanediamine, nonanediamine, decanediamine, malonic acid dihydrazide, succinic acid dihydrazide, glutaric acid dihydrazide, adipic acid dihydrazide, pimelic acid dihydrazide, suberic acid dihydrazide, azelaic acid dihydrazide, amino-PEG.

[0010] In some embodiments of the present application, the small molecule sunscreen agent is selected from any one of cinnamic acid, cinnamic acid derivative, salicylic acid, salicylic acid derivative, o-hydroxybenzoic acid, 4-diethylamino ketonic acid, 4-dimethylamino benzoic acid, 2,6-naphthalene dicarboxylic acid, 1,8-dihydroxy-3-carboxy anthraquinone.

[0011] In some embodiments of the present application, the modification rate of R1 of the polymer backbone is between 5% and 50%.

[0012] In some embodiments of the present application, the modification rate of R2 of the polymer backbone is between 10% and 50%.

[0013] In some embodiments of the present application, the molecular weight of the polymer is between 1000 Da and 5000000 Da.

[0014] In the second aspect of the present application, a sunscreen hydrogel is provided, comprising the above-mentioned photo-crosslinkable polymer with anti-ultraviolet effect, a photoinitiator and water.

[0015] In some embodiments of the present application, the concentration of the photo-crosslinkable polymer is between 2 and 10 wt%, the concentration of the photoinitiator is between 0.05 and 0.5 wt%, and the rest is water.

[0016] In some embodiments of the present application, the photoinitiator is selected from any one or more of lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, alpha-ketoglutaric acid, eosin Y, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, 1-hydroxycyclohexyl benzophenone.

[0017] In a third aspect, the present application provides a method for preparing the above-mentioned sunscreen hydrogel, which comprises dissolving a photo-crosslinkable polymer with anti-ultraviolet effect and a photoinitiator in water, and performing crosslinking reaction under irradiation of light with a wavelength of 200-800 nm for 2-180 s.

[0018] In a fourth aspect, the present application provides a method for preparing the above-mentioned photo-crosslinkable polymer with anti-ultraviolet effect, which comprises selecting any one of the following preparation methods a and b.

[0019] a. dissolving a natural polymer containing hydroxyl and / or amino groups, adding (meth)acrylic anhydride, and then performing sedimentation, filtration and drying to obtain a (meth)acrylic acid-modified polymer;

[0020] adding an activated small molecule sunscreen agent and a catalyst to the solution of the (meth)acrylic acid-modified polymer, and then performing sedimentation, filtration and drying;

[0021] b. dissolving a natural polymer containing carboxyl groups, adding an excess amount of a coupling agent, and then performing sedimentation, filtration and drying to obtain a polymer modified with amino or hydrazide at the carboxyl sites;

[0022] adding (meth)acrylic anhydride to the solution of the polymer modified with amino or hydrazide at the carboxyl sites, and then performing sedimentation, filtration and drying to obtain a (meth)acrylic acid-modified polymer;

[0023] adding an activated small molecule sunscreen agent and a catalyst to the solution of the (meth)acrylic acid-modified polymer, and then performing sedimentation, filtration and drying.

[0024] Preferably, the coupling agent in the preparation method b is selected from any one of ethylenediamine, propylenediamine, butylenediamine, pentanediamine, hexanediamine, heptanediamine, octanediamine, nonanediamine, decanediamine, malonic acid dihydrazide, succinic acid dihydrazide, glutaric acid dihydrazide, adipic acid dihydrazide, pimelic acid dihydrazide, suberic acid dihydrazide, sebacic acid dihydrazide, and amino-PEG.

[0025] Preferably, the preparation method a is specifically implemented by the following process: dissolving a polymer raw material containing hydroxyl and / or amino groups in water, adjusting the pH to 7-10, adding an appropriate amount of (meth)acrylic anhydride at 1-60°C, continuously stirring for 10-24 h, removing small molecule impurities by ethanol precipitation, deionized water dialysis or ultrafiltration after the reaction is completed, and then freeze-drying to obtain a (meth)acrylic acid-modified polymer; dissolving the (meth)acrylic acid-modified polymer, adding an activated cinnamic acid or cinnamic acid derivative and an appropriate amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, continuously stirring for 5-24 h, removing small molecule impurities by tetrahydrofuran sedimentation, deionized water dialysis or ultrafiltration, and then freeze-drying to obtain the final product.

[0026] Preferably, the preparation method b is specifically implemented by the following steps: dissolving the carboxyl-containing polymer raw material in water, adding excess adipic acid dihydrazide, adjusting the pH to 3-6, continuously stirring for 10-24 hours, after the reaction is completed, removing small molecular impurities by ethanol precipitation, deionized water dialysis or ultrafiltration, and obtaining the polymer modified at the carboxyl site after freeze-drying; dissolving the polymer in water, adjusting the pH to 7-10, adding an appropriate amount of (methyl) acrylate anhydride at 1-60 DEG C, continuously stirring for 10-24 hours, after the reaction is completed, removing small molecular impurities by ethanol precipitation, deionized water dialysis or ultrafiltration, and obtaining the (methyl) acrylate modified polymer after freeze-drying; dissolving the (methyl) acrylate modified polymer again, adding the cinnamic acid or cinnamic acid derivative activated by NHS and an appropriate amount of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, continuously stirring for 5-24 hours, removing small molecular impurities by tetrahydrofuran precipitation, deionized water dialysis or ultrafiltration, and obtaining the final product after freeze-drying.

[0027] In a fifth aspect, the application provides the use of the above-mentioned photo-crosslinkable polymer, which is selected from the following uses:

[0028] The use of the photo-crosslinkable polymer in ultraviolet protection products;

[0029] When R1 is selected from cinnamic acid or its derivative, the photo-crosslinkable polymer has the effects of scavenging free radicals, inhibiting lipid peroxidation, etc., and has application value in antioxidant products.

[0030] When R1 is selected from cinnamic acid or its derivative, the photo-crosslinkable polymer has the effects of destroying cell membranes, inhibiting enzyme activity, and interfering with DNA / RNA synthesis, and therefore has application value in antiseptic and sterilization products.

[0031] The photo-crosslinkable polymer with anti-ultraviolet effect, the preparation method and the application disclosed in the embodiments of the application connect small molecule compounds with anti-ultraviolet effect to the hydrophilic natural polymer skeleton through a chemical bond, and introduce a photo-crosslinkable (methyl) acryloyl group, thereby preparing a photo-crosslinkable polymer with anti-ultraviolet effect. After the solution of the photo-crosslinkable polymer with anti-ultraviolet effect is irradiated by light of a specific wavelength, the (methyl) acryloyl group is crosslinked and polymerized under the action of a photoinitiator, thereby forming a non-flowing hydrogel. The hydrogel forms a physical barrier at the contact site to block external ultraviolet irradiation or pollution. The anti-ultraviolet small molecule is connected to the crosslinked network through a chemical bond, thereby playing the sunscreen effect, and the mechanical strength of the gel network can resist water flow impact and the penetration of sweat, so that the sunscreen hydrogel of the application not only prolongs the residence time of the sunscreen molecule, but also reduces the safety risk of the penetration of the small molecule sunscreen into the skin.

[0032] In summary, the light-crosslinkable polymer with anti-ultraviolet effect of the present application contains multiple active modification sites such as hydroxyl, amino or carboxyl, which are respectively connected with (meth) acryloyl and functional groups with strong ultraviolet absorption such as small molecule sunscreen agents. Such polymer can not only be crosslinked to form a network structure under light conditions, resist water flow impact or sweat erosion, but also realize sunscreen gain effect and effectively avoid the safety risk of small molecule sunscreen agents penetrating into the skin. The (meth) acryloyl and sunscreen functional groups are simultaneously modified on the hydrophilic polymer, which has the characteristics of light-responsive crosslinking film formation and anti-ultraviolet effect, and can realize the triple effect of waterproof, sweat-proof and sunscreen.

[0033] It should be understood that the foregoing general description and the following detailed description are only exemplary and explanatory, and cannot limit the present disclosure. BRIEF DESCRIPTION OF DRAWINGS

[0034] The accompanying drawings incorporated in and forming a part of the specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the application;

[0035] Figure 1 Effect picture for the gelation performance test of the sunscreen hydrogel of the embodiment of the present application;

[0036] Figure 2 Effect picture for the ultraviolet absorption performance test of the sunscreen hydrogel of the embodiment;

[0037] Figure 3 Comparison picture for the ultraviolet absorption performance comparison test of the sunscreen hydrogel of the embodiment. DETAILED DESCRIPTION

[0038] The concept and technical effects of the present application will be described below in combination with embodiments to make the purpose, features and effects of the present application clear. Obviously, the described embodiments are only part of the embodiments of the present application, but not all the embodiments. Based on the embodiments of the present application, other embodiments obtained by those skilled in the art without creative labor are within the protection scope of the present application.

[0039] The experimental methods not specified in the embodiments are usually according to the conventional conditions or according to the suggested conditions of the manufacturers; the raw materials, reagents and the like used, if not specially specified, are the raw materials and reagents that can be obtained from the conventional market or other commercial channels.

[0040] Embodiment 1, preparation of light-crosslinkable polymer A1;

[0041] Step one: 2 g of sodium hyaluronate (Mw = 200~400 kDa) powder was dissolved in 400 mL of deionized water, an excess of adipic dihydrazide coupling agent and 2.05 g of EDC were added, the pH of the reaction system was adjusted to 4~5, and continuous stirring was carried out overnight. After the reaction was completed, the dialysis bag with MWCO = 20 kDa was dialyzed in a large amount of deionized water for 3 days, and then freeze-dried to obtain the sodium hyaluronate with side chain modified amino groups, with a yield of about 85%.

[0042] Step two: 5 g of p-nitrocinnamic acid was dissolved in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, and then an equimolar amount of NHS and EDC was added. The reaction was carried out in the dark for 24 h. After the reaction was completed, the generated by-product dicyclohexylurea was removed by filtration, and the filtrate was poured into water to precipitate. The obtained solid was vacuum dried and then recrystallized with DMF / ethanol to obtain N-succinimidyl p-nitrocinnamate with a yield of about 90%.

[0043] Step three: 0.4 g of the above-mentioned sodium hyaluronate with modified amino groups was dissolved in 50 mL of NaHCO3 solution with pH 8.3, and 40 mL of DMF was added dropwise at room temperature. A certain amount of N-succinimidyl cinnamate was dissolved in 10 mL of DMF and added dropwise to the above-mentioned solution. An excess of methacrylic anhydride was then added, and the reaction was carried out in the dark at room temperature for 72 h, during which the pH was maintained at 8-9 using NaOH solution. After the reaction was completed, the product was precipitated in excess tetrahydrofuran, filtered, and then vacuum dried after washing with THF to obtain the sodium hyaluronate modified with p-nitrocinnamic acid and methacryloyl A1, with a yield of about 80%.

[0044] Example 2, preparation of a photo-crosslinkable polymer A2;

[0045] The difference between the preparation method of Example 2 and Example 1 is only that the sodium hyaluronate in Example 1 is replaced by an equimolar amount of sodium alginate, and finally the sodium alginate modified with p-nitrocinnamic acid and methacryloyl A2 is obtained, with a yield of about 77%.

[0046] Example 3, preparation of a photo-crosslinkable polymer A3;

[0047] Step one: 5 g of salicylic acid was dissolved in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, and then an equimolar amount of NHS and EDC was added. The reaction was carried out in the dark for 24 h. After the reaction was completed, the generated by-product dicyclohexylurea was removed by filtration, and the filtrate was poured into water to precipitate. The obtained solid was vacuum dried and then recrystallized with DMF / ethanol to obtain N-succinimidyl salicylate.

[0048] Step two: Take 5 g of gelatin, dissolve in 50 mL of NaHCO3 solution with pH 8.3 at 50 °C, drop 40 mL of DMF at room temperature, dissolve a certain amount of N-succinimidyl salicylate in 10 mL of DMF, drop into the above solution, add a suitable amount of methacrylic anhydride, react at room temperature for 72 h in the dark, and maintain pH 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain salicylic acid and methacryl-modified gelatin A3 with a yield of about 80%.

[0049] Example 4, preparation of photo-crosslinkable polymer A4;

[0050] The difference between the preparation method of Example 4 and Example 3 is that the gelatin in Example 3 is replaced with collagen of equal molar amount, and finally collagen A4 modified by salicylic acid and methacryl group is obtained with a yield of about 83%.

[0051] Example 5, preparation of photo-crosslinkable polymer A5;

[0052] Step one: Dissolve 5 g of o-hydroxybenzoic acid in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, then add equal molar amount of NHS and EDC, and react in the dark for 24 h. After the reaction is completed, remove the generated by-product dicyclohexylurea by filtration, precipitate the filtrate in water, vacuum dry the obtained solid, and then recrystallize it with DMF / ethanol to obtain N-succinimidyl o-hydroxybenzoate.

[0053] Step two: Dissolve 2 g of hydroxyethyl chitosan in 200 mL of NaHCO3 solution with pH 8.3, drop 40 mL of DMF at room temperature, dissolve a certain amount of N-succinimidyl o-hydroxybenzoate in 10 mL of DMF, drop into the above solution, add a suitable amount of methacrylic anhydride, react at room temperature for 72 h in the dark, and maintain pH 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain o-hydroxybenzoic acid and methacryl-modified chitosan A5.

[0054] Example 6, preparation of photo-crosslinkable polymer A6;

[0055] Step one: Dissolve 5 g of 4-diethylaminoketone acid in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, then add equal molar amount of NHS and EDC, and react in the dark for 24 h. After the reaction is completed, remove the generated by-product dicyclohexylurea by filtration, precipitate the filtrate in water, vacuum dry the obtained solid, and then recrystallize it with DMF / ethanol to obtain N-succinimidyl 4-diethylaminoketone ester.

[0056] Step two: take 2 g of carboxymethyl chitosan, dissolve in 200 mL of NaHC03 solution with pH 8.3, drop 40 mL of DMF at room temperature, dissolve a certain amount of N-succinimidyl 4-dimethylaminobenzoate in 10 mL of DMF, drop into the above solution, then add excess methacrylic anhydride, react for 72 h at room temperature in the dark, and maintain pH 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain carboxymethyl chitosan modified with 4-dimethylaminobenzoic acid and methacryl group A6.

[0057] Example 7, preparation of photo-crosslinkable polymer A7;

[0058] Step one: weigh 2 g of carboxymethyl cellulose powder, dissolve in 400 mL of deionized water, add excess hexanediamine and 2.05 g of EDC, adjust the pH of the reaction system to 4-5, continuously stir overnight, after the reaction is completed, dialyze in a large amount of deionized water using a dialysis bag with MWCO = 10 kDa for 3 days, and then freeze-dry to obtain carboxymethyl cellulose modified with amino groups on the side chain.

[0059] Step two: dissolve 5 g of 4-dimethylaminobenzoic acid in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, then add equimolar amounts of NHS and EDC, and react in the dark for 24 h. After the reaction is completed, filter out the generated by-product dicyclohexylurea, pour the filtrate into water to precipitate, vacuum dry the obtained solid, and then recrystallize with DMF / ethanol to obtain N-succinimidyl 4-dimethylaminobenzoate.

[0060] Step three: take 0.4 g of the carboxymethyl cellulose modified with amino groups above, dissolve in 50 mL of NaHC03 solution with pH 8.3, drop 40 mL of DMF at room temperature, dissolve a certain amount of N-succinimidyl 4-dimethylaminobenzoate in 10 mL of DMF, drop into the above solution, then add excess methacrylic anhydride, react for 72 h at room temperature in the dark, and maintain pH 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain cellulose modified with 4-dimethylaminobenzoic acid and methacryl group A7.

[0061] Example 8, preparation of photo-crosslinkable polymer A8;

[0062] Step one: 2 g of chondroitin sulfate was dissolved in 400 mL of deionized water, and an excess of butanediamine coupling agent and 2.05 g of EDC were added. The pH of the reaction system was adjusted to 4-5, and stirring was continued overnight. After the reaction was completed, dialysis was performed in a large amount of deionized water using a dialysis bag with a MWCO of 10 kDa for 3 days. After freeze-drying, the side chain modified amino chondroitin sulfate was obtained.

[0063] Step two: 5 g of 2,6-naphthalene dicarboxylic acid was dissolved in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, and an equimolar amount of NHS and EDC was added. The reaction was carried out in the dark for 24 h. After the reaction was completed, the generated by-product dicyclohexylurea was removed by filtration, and the filtrate was poured into water to precipitate. The obtained solid was vacuum dried and recrystallized with DMF / ethanol to obtain N-succinimidyl 2,6-naphthalene dicarboxylate.

[0064] Step three: 0.4 g of the above modified amino chondroitin sulfate was dissolved in 50 mL of a NaHCO3 solution with a pH of 8.3, and 40 mL of DMF was added dropwise at room temperature. A certain amount of N-succinimidyl 2,6-naphthalene dicarboxylate was dissolved in 10 mL of DMF and added dropwise to the above solution. An excess of methacrylic anhydride was added, and the reaction was carried out in the dark at room temperature for 72 h, during which the pH was maintained at 8-9 using a NaOH solution. After the reaction was completed, precipitation was performed in an excess of tetrahydrofuran, and the solid was washed with THF and then vacuum dried to obtain 2,6-naphthalene dicarboxylic acid and methacryloyl-modified chondroitin sulfate A8.

[0065] Example 9, Preparation of a photo-crosslinkable polymer A9;

[0066] Step one: 2 g of sodium hyaluronate (Mw = 200-400 kDa) powder was dissolved in 400 mL of deionized water, and an excess of glutaric acid dihydrazide coupling agent and 2.05 g of EDC were added. The pH of the reaction system was adjusted to 4-5, and stirring was continued overnight. After the reaction was completed, dialysis was performed in a large amount of deionized water using a dialysis bag with a MWCO of 20 kDa for 3 days. After freeze-drying, the side chain modified hyaluronic acid was obtained.

[0067] Step two: 5 g of 1,8-dihydroxy-3-carboxy anthraquinone was dissolved in 50 mL of N, N'-dimethylformamide (DMF) at 40 °C, and an equimolar amount of NHS and EDC was added. The reaction was carried out in the dark for 24 h. After the reaction was completed, the generated by-product dicyclohexylurea was removed by filtration, and the filtrate was poured into water to precipitate. The obtained solid was vacuum dried and recrystallized with DMF / ethanol to obtain N-succinimidyl 1,8-dihydroxy-3-carboxy anthraquinone ester.

[0068] Step three: take 0.4 g of the above modified hyaluronic acid sodium hydrazide, dissolve in 50 mL of NaHCO3 solution with pH 8.3, add 40 mL of DMF dropwise at room temperature, dissolve a certain amount of N-succinimidyl 1,8-dihydroxy-3-carboxy anthraquinone ester in 10 mL of DMF, add it to the above solution, then add excess methacrylic anhydride, react at room temperature for 72 h in the dark, and maintain the pH at 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain 1,8-dihydroxy-3-carboxy anthraquinone and methacryloyl-modified hyaluronic acid sodium A9.

[0069] Example 10, preparation of a photo-crosslinkable polymer A10;

[0070] Step one: weigh 2 g of hyaluronic acid sodium (Mw = 200-400 kDa) powder, dissolve in 400 mL of deionized water, add excess azelaic acid dihydrazide coupling agent and 2.05 g of EDC, adjust the pH of the reaction system to 4-5, continuously stir overnight, after the reaction is completed, dialyze in a large amount of deionized water with a MWCO = 20 kDa dialysis bag for 3 days, and then freeze-dry to obtain hyaluronic acid sodium modified with amino groups on the side chain.

[0071] Step two: dissolve 5 g of p-methoxycinnamic acid in 50 mL of N, N'-dimethylformamide (DMF) at 40°C, then add equimolar amounts of NHS and EDC, and react in the dark for 24 h. After the reaction is completed, filter out the generated by-product dicyclohexylurea, pour the filtrate into water to precipitate, vacuum dry the obtained solid, and then recrystallize with DMF / ethanol to obtain N-succinimidyl p-methoxycinnamate.

[0072] Step three: take 0.4 g of the above modified hyaluronic acid sodium hydrazide, dissolve in 50 mL of NaHCO3 solution with pH 8.3, add 40 mL of DMF dropwise at room temperature, dissolve a certain amount of N-succinimidyl p-methoxycinnamate in 10 mL of DMF, add it to the above solution, then add excess methacrylic anhydride, react at room temperature for 72 h in the dark, and maintain the pH at 8-9 with NaOH solution during the reaction. After the reaction is completed, precipitate in excess tetrahydrofuran, filter, wash the solid with THF, and then dry in vacuum to obtain p-methoxycinnamic acid and methacryloyl-modified hyaluronic acid sodium.

[0073] The coupling agent used in each example can be selected from any one of ethylenediamine, propylenediamine, butylenediamine, pentanediamine, hexanediamine, heptanediamine, octanediamine, nonanediamine, decanediamine, malonic acid dihydrazide, succinic acid dihydrazide, glutaric acid dihydrazide, adipic acid dihydrazide, pimelic acid dihydrazide, suberic acid dihydrazide, azelaic acid dihydrazide, sebacic acid dihydrazide, and terminal aminated PEG.

[0074] Example 11, preparation of sunscreen hydrogel;

[0075] The polymers A1-A10 are respectively dissolved in water with a concentration range of 2wt%-10wt%, 0.05wt%-0.5wt% of a photoinitiator is added, to obtain sunscreen hydrogel, wherein the initiator is selected from any one of the following: lithium phenyl (2,4,6-trimethylbenzoyl) phosphate (LAP), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, alpha-ketoglutaric acid, eosin Y, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, 1-hydroxycyclohexyl benzophenone.

[0076] Comparative Example 1: p-nitro cinnamic acid is dissolved in DMSO at a concentration of 2wt%.

[0077] Comparative Example 2: salicylic acid is dissolved in DMSO at a concentration of 2%.

[0078] Test Example 1: Anti-ultraviolet efficacy performance test of photo-crosslinkable polymers A1-A10 with anti-ultraviolet efficacy

[0079] A1-A10 are respectively configured into a 0.1% aqueous solution, comparative example 1 and comparative example 2 are respectively diluted with DMSO to 0.1%, and a UV spectrophotometer is used to scan in the range of 200nm-800nm, and the obtained UV absorption peak range is shown in Table 1:

[0080] Table 1

[0081] Polymer Ultraviolet absorption range (nm) A1 260~380 A2 260~380 A3 250~360 A4 250~360 A5 210~250 A6 310~390 A7 230~320 A8 310~365 A9 240~320 A10 270~350 Comparative Example 1 250~360 Comparative Example 2 250~360

[0082] As shown in Table 1, the photo-crosslinkable polymer has the function of absorbing ultraviolet rays and has anti-ultraviolet efficacy. It is illustrated that the small molecule compound with anti-ultraviolet efficacy is connected to the hydrophilic natural polymer skeleton by chemical bond, and the (methyl) propylene double bond is introduced, compared with the single small molecule compound with anti-ultraviolet efficacy (ultraviolet absorption range 250-360nm), the comparative example 1 and the comparative example 2, the photo-crosslinkable polymer with anti-ultraviolet efficacy (ultraviolet absorption range 210-390nm) can be prepared.

[0083] Test Example 2: Compression modulus and ultraviolet transmittance test of sunscreen hydrogel

[0084] The sunscreen hydrogel with different concentrations of components is irradiated with 405nm ultraviolet light, and the sunscreen hydrogel is cured to form a sunscreen hydrogel in about 30s.

[0085] The compression modulus was measured using a WDF-20 digital force gauge. The compression test specimens were cylindrical specimens with a diameter of 10 mm and a height of 3 mm. The test speed was 1 mm / min. The compression modulus of the sunscreen hydrogels is shown in Table 2.

[0086] Evenly apply 2 ml of the A1-A10 polymer aqueous solution to a 5 cm x 5 cm transparent PMMA plate. Place the PMMA plate 2 cm above a TM-223 (TENMARS) UV light meter and illuminate it directly above the plate with a 365 nm UV lamp. Record the UV intensity detected by the UV light meter, using the blank PMMA plate as a reference (100%). The data are reported in Table 2. As can be seen from Table 2, the A1-A10 polymer aqueous solutions all exhibit good UV protection.

[0087] Table 2

[0088] Sunscreen water gel (component concentration) Compression modulus (kPa) Ultraviolet transmittance A1 : 2 wt%; initiator: 0.5 wt% 42 9.7% A2: 2 wt%; initiator: 0.5 wt% 45 10.1% A3: 10 wt%; initiator: 0.5 wt% 62 14.3% A4: 10 wt%; initiator: 0.5 wt% 54 14.7% A5: 2 wt%; initiator: 0.5 wt% 39 17.2% A6: 2 wt%; initiator: 0.5 wt% 35 13.5% A7: 2 wt%; initiator: 0.5 wt% 39 15.4% A8: 2 wt%; initiator: 0.5 wt% 45 13.2% A9: 2 wt%; initiator: 0.5 wt% 43 16.1% A10: 2 wt%; initiator: 0.5 wt% 40 17.3% A1 : 2 wt%; initiator: 0.05 wt% 20 9.6% A1 : 2 wt%; initiator: 0.2 wt% 31 9.7% A1 : 3 wt%; initiator: 0.5 wt% 50 9.7%

[0089] The values ​​of the compression modulus in Table 2 indicate that under the action of the photoinitiator, a cross-linking polymerization reaction of the (meth)propylene double bonds in the photocross-linked polymer is initiated to form a non-flowing hydrogel. The mechanical strength of the gel network can resist the impact of running water and the penetration of sweat, which can prolong the retention time of sunscreen molecules on the skin surface and reduce the safety risks brought by the penetration of small molecule sunscreens into the skin.

[0090] Test Example 2: Gelation Performance Test of Sunscreen Hydrogel

[0091] According to the method of Example 11, sunscreen hydrogels with different concentrations of components were prepared. Any component was selected and irradiated with light of 405 nm wavelength. The flowing sunscreen hydrogel solidified into a non-flowing sunscreen hydrogel in about 10 seconds. Figure 1 As shown (the sunscreen hydrogel components shown in the figure: A1: 2wt%; initiator: 0.5wt%).

[0092] Test Example 3: UV absorption performance test of sunscreen hydrogel

[0093] According to the method of Example 11, sunscreen hydrogels with different concentrations of components were prepared. Any group of sunscreen hydrogels: A1: 2wt%; initiator: 0.5wt% were selected and added dropwise to the sensing area of ​​the UV sunscreen card. The UV light was used for irradiation. Figure 2 As shown in the figure (the sunscreen hydrogel components shown are: A1: 2wt%; initiator: 0.5wt%)), when exposed to UV light, the sensing area, excluding the sunscreen hydrogel, becomes noticeably darker due to absorption of UV light. After removing the sunscreen hydrogel, it is clearly visible that the area coated with the sunscreen hydrogel has essentially no color change, proving that the hydrogel absorbs UV light. This demonstrates that the sunscreen hydrogel has a significant UV shielding effect on the UV sensor card.

[0094] Test Example 4: Comparative test of ultraviolet absorption performance of sunscreen hydrogel

[0095] According to the method of Example 11, sunscreen hydrogels of different concentrations of components are prepared, and any one of the sunscreen hydrogels is selected and added dropwise on the right side of the ultraviolet sunscreen card sensing area, and Comparative Example 1 is added dropwise on the left side of the ultraviolet sunscreen card sensing area. Under ultraviolet light irradiation, the polymer solution on the right side is crosslinked to form a non-flowing gel. As shown in the figure (the components of the sunscreen hydrogel shown in the figure: A1: 2wt%; initiator: 0.5wt%), when ultraviolet light irradiation is performed, the sensing area is discolored due to the absorption of ultraviolet light, except for the area of Comparative Example 1 solution and sunscreen hydrogel. After the ultraviolet sunscreen card is soaked in water for 10 minutes, the Comparative Example 1 solution is washed away by water, while the gel remains unchanged. When ultraviolet light irradiation is performed again, the area on the ultraviolet sunscreen card coated with the gel does not change color, and after the sunscreen hydrogel is removed, the color contrast change can be clearly seen. Further indicating that the sunscreen hydrogel has significant waterproof effect and long-lasting ultraviolet protection effect. Figure 3 Example 12: Application of photo-crosslinkable polymer in ultraviolet protection products

[0096] The photo-crosslinkable polymers prepared in Examples 1-10 can be seen to have ultraviolet absorption function in the range of 210-390nm by performing ultraviolet absorption test 1. The polymers A1-A10 are dissolved in water respectively, with a concentration range of 2wt%-10wt%, and 0.05wt%-0.5wt% of a photo initiator is added to obtain a sunscreen hydrogel, which can be used in ultraviolet protection products. The effect of the ultraviolet protection products is evaluated by the elastic modulus and ultraviolet transmittance of the sunscreen hydrogel, the gelation performance test example 3, and the ultraviolet absorption performance test example 4.

[0097] Example 13: Application of photo-crosslinkable polymer in antioxidant products

[0098] The photo-crosslinkable polymers obtained in Examples 1 and 2 have small molecule compounds with ultraviolet protection effect connected to the hydrophilic natural polymer skeleton by chemical bonding, and (meth) acryloyl groups are introduced, which have the effects of scavenging free radicals, inhibiting lipid peroxidation, etc., and have application value in antioxidant products.

[0099] Example 14: Application of photo-crosslinkable polymer in antiseptic and sterilization products

[0100]

[0101] ​The small molecule compound with anti-ultraviolet effect is connected to the hydrophilic natural polymer skeleton by chemical bonding in the light-crosslinkable polymer obtained in Embodiments 1 and 2, and a light-crosslinkable (meth) acryl group is introduced, which has the application value in the antiseptic and sterilization product by destroying cell membrane, inhibiting enzyme activity and interfering with DNA / RNA synthesis.

[0102] The technical features of the above embodiments can be combined arbitrarily, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, however, as long as the combinations of the technical features do not exist contradictory, they should be considered as the scope of the description.

[0103] The above embodiments only express several implementation manners of the present application, the description is more specific and detailed, but it should not be understood as the limitation of the patent scope of the present application. It should be pointed out that for ordinary skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A sunscreen hydrogel, characterized in that: comprising a photocrosslinkable polymer having UV resistance, a photoinitiator and water; The method for preparing the photocrosslinkable polymer with anti-ultraviolet efficacy is selected from any one of the following preparation methods a and b: a. The natural polymer containing hydroxyl groups and / or amino groups is dissolved and then (meth) acrylic anhydride is added. After the reaction, the mixture is settled, filtered, and dried to obtain a (meth) acrylic acid-modified polymer. Add the activated carboxyl-containing small molecule sunscreen and catalyst to the (meth)acrylic acid modified polymer solution, and then react, settle, filter and dry. b. dissolving the natural carboxyl-containing polymer and adding an excess coupling agent, settling the reaction, filtering, and drying to obtain a polymer modified with an amino group or hydrazide at the carboxyl site; (Meth) acrylic acid anhydride is added to a polymer solution modified with an amino group or hydrazide at a carboxyl site, and after reaction, the solution is precipitated, filtered, and dried to obtain a (meth) acrylic acid-modified polymer; Add the activated carboxyl-containing small molecule sunscreen and catalyst to the (meth)acrylic acid modified polymer solution, and then react, settle, filter and dry. The natural polymer is selected from any one of hyaluronic acid, alginic acid, gelatin, collagen, chitosan, cellulose and chondroitin sulfate.

2. The sunscreen hydrogel according to claim 1, characterized in that The carboxyl-containing small molecule sunscreen comprises at least one of cinnamic acid, cinnamic acid derivatives, salicylic acid, salicylic acid derivatives, o-hydroxybenzoic acid, and 4-dimethylaminobenzoic acid.

3. The sunscreen hydrogel according to claim 1, characterized in that The coupling agent is selected from any one of ethylenediamine, propylenediamine, butylenediamine, pentamethylenediamine, hexamethylenediamine, heptamethylenediamine, octanediamine, nonanediamine, malonic acid dihydrazide, succinic acid dihydrazide, glutaric acid dihydrazide, adipic acid dihydrazide, pimelic acid dihydrazide, suberic acid dihydrazide, azelaic acid dihydrazide, sebacic acid dihydrazide, and amino PEG.

4. The sunscreen hydrogel according to claim 1, characterized in that The modification rate of the small molecule sunscreen agent in the photocrosslinkable polymer with anti-ultraviolet efficacy is between 5% and 50%, and / or the modification rate of the (meth)acrylic acid in the photocrosslinkable polymer with anti-ultraviolet efficacy is between 10% and 50%.

5. The sunscreen hydrogel according to claim 1, characterized in that The molecular weight of the natural polymer is 1000Da~5000000Da.

6. The sunscreen hydrogel according to claim 1, characterized in that The photoinitiator is selected from any one or more of phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, α-ketoglutaric acid, eosin Y, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, and 1-hydroxycyclohexyl benzophenone.

7. The sunscreen hydrogel according to claim 1, characterized in that The concentration of the photo-crosslinkable polymer with anti-ultraviolet effect is 2-10 wt %, the concentration of the photoinitiator is 0.05-0.5 wt %, and the rest is water.

8. The method for preparing the sunscreen hydrogel according to claim 1, wherein: The photo-crosslinkable polymer with anti-ultraviolet effect and the photoinitiator are dissolved in water, and a cross-linking reaction is carried out for 2 to 180 seconds under 200nm-800nm ​​light irradiation to obtain the product.

9. The use of the sunscreen hydrogel according to any one of claims 1 to 7, characterized in that: Application of the sunscreen hydrogel in the preparation of non-therapeutic ultraviolet protection products.

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