Huckleberry whitening and freckle-removing hydrogel emplastrum and preparation method thereof

Abstract

The invention discloses a huckleberry whitening and freckle removing hydrogel emplastrum and a preparation method thereof, and belongs to the technical field of skin care products. According to the orange whitening and freckle removing hydrogel emplastrum disclosed by the invention, natural antioxidant components rich in the bilberry extract are utilized, so that free radicals can be effectively removed, and the generation of melanin is inhibited, so that the whitening and freckle removing effects are achieved; the temperature-sensitive microcapsules coated with the bilberry extract can realize slow-controlled release of active ingredients after reaching the body temperature of a human body, can prolong the action time of the medicine, and achieves the effects of whitening and removing freckles for a long time.

Description

Technical Field

[0001] The invention relates to the technical field of skin care products, and in particular to a blueberry whitening and freckle-removing hydrogel plaster and a preparation method thereof. Background Art

[0002] Melanin is mainly produced by melanocytes in the basal layer of the human epidermis. It plays a vital role in protecting the skin from ultraviolet radiation and oxidative stress caused by external pollutants. When the skin is overexposed to sunlight, tyrosinase in the melanocytes in the basal layer of the skin is activated, converting tyrosine in the cells into melanin. Excessive secretion of melanin will gradually transfer to keratinocytes, causing the skin to darken. Abnormal accumulation of melanin in the basal layer will cause excessive pigmentation, causing chloasma, black spots, freckles, age spots, etc., affecting people's quality of life.

[0003] At present, there are many ways to improve and treat melasma, melasma, freckles, and age spots, such as Chinese medicine decoction conditioning, taking and applying chemical drugs with anti-inflammatory, antioxidant, and whitening effects, and laser and other means. Among them, Chinese medicine decoctions are often bitter, inconvenient to take, and have a long course of treatment. Long-term use of chemical drugs with anti-inflammatory, antioxidant, and whitening effects will have certain side effects on the human body, and laser therapy is expensive and prone to pigmentation.

[0004] Chinese patent document CN108042412A provides a whitening and spot-lightening essence and a preparation method thereof, which is prepared by mixing hyaluronic acid, butanediol, sodium sulfite, citric acid, acetyltyrosine, fullerene, aminopropanol ascorbyl phosphate, glutathione, arbutin, daisy flower extract, strawberry saxifrage extract, peony root extract, scutellaria root extract, Korean pulsatilla extract, Polygonum cuspidatum root extract and deionized water. The invention is mild to the skin, can effectively take into account the whitening and spot-lightening functions, and has the effect of nourishing the skin at the same time, through the whitening and spot-lightening components quickly penetrate into the skin, inhibit the activity of tyrosinase, effectively block the formation of melanin, reduce pigmentation, accelerate the decomposition and excretion of melanin, keep the skin soft and supple for a long time, activate skin cells, and improve the antioxidant property of the skin. The essence coating prepared by the invention is easy to evaporate on the skin, has a short action time, and is easily oxidized when exposed to the air, and it is difficult to maintain the effect for a long time. Summary of the invention

[0005] The main purpose of the present invention is to provide a bilberry whitening and freckle-removing hydrogel patch and a preparation method thereof, using bilberry extract as an active component, and coating the bilberry extract with a composite microcapsule, so that the bilberry extract can be released at a relatively stable rate, and the stability of the active substances in the bilberry extract can be effectively protected, the action time of the bilberry extract is prolonged, and the whitening and freckle-removing effect of the bilberry whitening and freckle-removing hydrogel patch is improved.

[0006] To achieve the above-mentioned purpose, the present invention proposes a bilberry whitening and freckle-removing hydrogel patch, comprising a backing layer, a matrix layer and an anti-sticking layer; the backing layer is a non-woven fabric, and the anti-sticking layer is one of release paper, a polypropylene film, and a polyethylene film; the matrix layer is applied on the backing layer, and the anti-sticking layer covers the matrix layer; the matrix layer comprises the following components in mass percentage: 2-8% polymer skeleton material, 1-5% viscosity enhancer, 0.1-1% cross-linking agent, 10-20% moisturizer, 0.5-1% preservative, 1-5% penetration enhancer, 1-3% anhydrous ethanol, 0.1-1% pH adjuster, 7-15% bilberry extract microcapsules, and the balance is deionized water.

[0007] Preferably, the polymer skeleton material is at least one of carbomer, sodium carboxymethyl cellulose, sodium alginate and sodium hyaluronate.

[0008] Preferably, the viscosity enhancer is at least one of gelatin, carboxymethyl cellulose and polyvinyl pyrrolidone.

[0009] Preferably, the cross-linking agent is at least one of aluminum oxide, alum, calcium chloride and calcium sulfate.

[0010] Preferably, the moisturizer is at least one of glycerol, propylene glycol and butylene glycol.

[0011] Preferably, the preservative is sodium benzoate.

[0012] Preferably, the penetration enhancer is eucalyptus oil and / or oleic acid.

[0013] Preferably, the pH adjuster is sodium hydroxide.

[0014] Preferably, the preparation method of the bilberry extract microcapsule is as follows: dissolving the bilberry extract with deionized water to obtain a bilberry extract aqueous solution, then immersing the composite microcapsule in the bilberry extract aqueous solution for oscillation dialysis, filtering, collecting the solid, washing it with deionized water, and drying it to obtain the bilberry extract microcapsule.

[0015] Bilberry (Vaccinium vitis-idaea L.) is a plant of the genus Vaccinium in the family Ericaceae. Bilberry extract contains active substances such as vitamin C, vitamin E, anthocyanins, arbutin and flavonoids, which help inhibit the production of melanin, regulate the metabolic rate of the skin, and promote cell renewal. These effects make the skin more tender, smooth and bright in color. The present invention uses composite microcapsule technology to wrap the bilberry extract in the structure of the composite microcapsule to form a stable microcapsule system. The sustained-release properties of the microcapsule can control the release rate of the bilberry extract, and the natural antioxidant components rich in the bilberry extract can effectively remove free radicals and inhibit the production of melanin, thereby achieving the effect of whitening and removing freckles. The sustained-release properties of the bilberry extract microcapsule enable the active ingredients to be continuously released, prolong the efficacy time, and enhance the effect of whitening and removing freckles.

[0016] Preferably, the preparation method of the bilberry extract is as follows:

[0017] The dried, crushed and sieved blueberry stems and leaves are added to a low eutectic solvent, subjected to ultrasonic treatment, and then subjected to heating extraction, cooled, and filtered to separate a filtrate 1 and a filter residue, and the filter residue is added to an aqueous solution containing dodecyl dimethyl betaine, subjected to ultrasonic extraction, filtered, and a filtrate 2 is collected; the filtrate 1 and the filtrate 2 are combined, and then concentrated under reduced pressure, and then ethanol is added to the concentrate for alcohol precipitation, and the precipitate is separated by centrifugation and freeze-dried to obtain a blueberry extract.

[0018] Preferably, the deep eutectic solvent is a mixture of choline chloride and sodium acetate.

[0019] Preferably, the preparation method of the composite microcapsule is as follows: calcining montmorillonite and then impregnating it with an alkaline solution, filtering, washing, drying and adding it to an ethanol aqueous solution after the impregnation is completed, adding KH550, heating and stirring, filtering, collecting the solid, washing and drying, adding it to water, adding 2-aminocinnamic acid, carboxymethyl gellan gum, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, adjusting the pH value to acidic, heating to react to obtain, filtering, collecting the solid, washing and drying to obtain modified montmorillonite; adding the modified montmorillonite and N-isopropylacrylamide to anhydrous ethanol, adding ammonium persulfate, heating to react, centrifuging, collecting the solid, washing and drying to obtain a composite microcapsule.

[0020] Preferably, the mass ratio of the montmorillonite, KH550, 2-aminocinnamic acid, carboxymethyl gellan gum, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 20-30:3-5:6-8:10-15:1-3; the mass ratio of the modified montmorillonite, N-isopropylacrylamide, and ammonium persulfate is 1-2:3-4:0.1-0.3.

[0021] Preferably, the preparation method of the carboxymethyl gellan gum is as follows: gellan gum, sodium hydroxide aqueous solution and ethanol aqueous solution are mixed and stirred evenly, chloroacetic acid aqueous solution is added, heated for reaction, cooled, filtered, the filter cake is dissolved with water, and then anhydrous ethanol is added thereto for precipitation, filtered, and the filter cake is washed and dried to obtain carboxymethyl gellan gum.

[0022] The present invention also discloses a method for preparing the blueberry whitening and freckle-removing hydrogel patch, which comprises the following steps:

[0023] The components are weighed according to the formula, and the polymer skeleton material, viscosity enhancer, cross-linking agent, moisturizer, preservative, penetration enhancer, anhydrous ethanol, pH adjuster, bilberry extract microcapsule and deionized water are evenly mixed and then subjected to vacuum degassing to obtain a whitening and freckle-removing liquid, and then the whitening and freckle-removing liquid is coated on a non-woven fabric by a machine, and then covered with an anti-sticking layer, and then cut and trimmed after curing to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1) The bilberry whitening and freckle-removing hydrogel patch obtained by the present invention utilizes the natural antioxidant components rich in bilberry extract to effectively remove free radicals and inhibit the formation of melanin, thereby achieving the effect of whitening and freckle removal; the thermosensitive microcapsules coated with bilberry extract can realize the slow and controlled release of active ingredients after reaching a certain temperature, thereby achieving the effect of long-term whitening and freckle removal;

[0026] 2) In the extraction process of the bilberry extract of the present invention, the bilberry stems and leaves are first crushed, which is conducive to the full release of the extracted components and improves the extraction efficiency; through a large number of extraction solvents, a choline chloride and sodium acetate system is finally selected; due to the application of a low eutectic solvent, the extraction effect is greatly improved, and the combined use of the low eutectic solvent and ultrasonic extraction has a good extraction effect. The small amount of extracted components remaining in the filter residue are extracted using an aqueous solution of dodecyl dimethyl betaine, which can promote the full release of the residual bilberry extract effective components, cooperate with ultrasonic treatment, and further improve the extraction efficiency;

[0027] 3) The composite microcapsule of the present invention is based on modified montmorillonite as the core. Montmorillonite itself has a large specific surface area and good adsorption properties, and can adsorb active substances. By modifying it, the release rate of the active substances can be regulated and the active substances can be protected. The preparation of the composite microcapsule is first to treat the surface of the montmorillonite with KH550 to introduce amino groups, and then react with 2-aminocinnamic acid and carboxymethyl gellan gum to graft 2-aminocinnamic acid and carboxymethyl gellan gum on the montmorillonite. By introducing 2-aminocinnamic acid into the composite microcapsule, the influence of the external environment (light, oxygen) on the active components (arbutin, vitamin E, anthocyanins, etc.) can be effectively prevented, thereby protecting the active ingredients of the bilberry extract, improving the stability of the bilberry extract, and giving the composite microcapsule anti-inflammatory and antioxidant properties. The invention discloses a novel nanostructured microcapsule comprising a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. The nanostructured microcapsule comprises a nanostructured microcapsule and a nanostructured microcapsule. DETAILED DESCRIPTION

[0028] To avoid redundancy, the items used in the following examples are all commercially available products unless otherwise specified, and the methods used are all conventional methods unless otherwise specified.

[0029] The sources of some raw materials used in the present invention are as follows:

[0030] Montmorillonite, 325 mesh, with a silica content of 55-65%, was purchased from Shijiazhuang Deze Mineral Products Co., Ltd.

[0031] Mouse melanoma B16-F10 cells were purchased from Shanghai Binsui Biotechnology Co., Ltd.

[0032] Example 1

[0033] A method for preparing a blueberry whitening and freckle-removing hydrogel patch comprises the following steps:

[0034] S1. Mix 5g of carbomer 940, 3g of gelatin, 0.5g of aluminum oxide, 13.8g of glycerin, 0.8g of sodium benzoate, 3g of eucalyptus oil, 2g of anhydrous ethanol, 0.5g of sodium hydroxide, 12g of bilberry extract microcapsules, and 59.4g of deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0035] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0036] The preparation method of the bilberry extract is as follows:

[0037] 1200g of choline chloride and 400g of sodium acetate were mixed and stirred at 80°C for 4 hours to obtain a low eutectic solvent. 100g of blueberry stems and leaves were dried, crushed and passed through an 80-mesh sieve, and then added to the low eutectic solvent. After ultrasonic treatment at a power of 150W for 8min, the mixture was heated and extracted at 60°C for 4h. The filtrate 1 and the residue were separated by cooling and filtration. The residue was added to 1000g of an aqueous solution containing 8wt% dodecyl dimethyl betaine. After ultrasonic extraction at a power of 150W for 8min, the mixture was filtered and filtrate 2 was collected. Filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume. Then, 500mL of anhydrous ethanol was added to the concentrate for alcohol precipitation. The precipitate was separated by centrifugation and freeze-dried to obtain a blueberry extract.

[0038] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 16g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 28g of 2-aminocinnamic acid, 48g of carboxymethyl gellan gum, and 8g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated at 60°C for reaction for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 70g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 4g of ammonium persulfate is added, and the mixture is heated at 60°C for reaction for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0039] The preparation method of the carboxymethyl gellan gum is as follows:

[0040] At 30°C, 10 g of gellan gum, 60 mL of 3 mol / L sodium hydroxide aqueous solution, and 230 mL of 99 wt% ethanol aqueous solution were mixed and stirred for 30 min; 50 g of monochloroacetic acid was added and stirred for 20 min to obtain a mixed solution; the mixed solution was heated to 60°C and reacted for 12 h; the mixed solution was cooled to 30°C and filtered, the filter cake was dissolved with 5 times the mass of water, and then anhydrous ethanol was added thereto for precipitation, filtered, the filter cake was washed with methanol and dried at 50°C for 12 h to obtain carboxymethyl gellan gum.

[0041] Example 2

[0042] A method for preparing a blueberry whitening and freckle-removing hydrogel patch comprises the following steps:

[0043] S1. Mix 2g sodium carboxymethyl cellulose, 1g polyvinyl pyrrolidone, 0.1g alum, 10g propylene glycol, 0.5g sodium benzoate, 1g oleic acid, 1g anhydrous ethanol, 0.1g sodium hydroxide, 7g bilberry extract microcapsules, and 77.3g deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0044] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0045] The preparation method of the bilberry extract is as follows:

[0046] 1200g of choline chloride and 400g of sodium acetate were mixed and stirred at 80°C for 4 hours to obtain a low eutectic solvent, 100g of blueberry stems and leaves were dried, crushed and sieved, and then added to the low eutectic solvent, ultrasonically treated at a power of 150W for 8min, and then heated and extracted at 60°C for 4h, cooled and filtered to separate filtrate 1 and residue, and the residue was added to 1000g of an aqueous solution containing 8wt% dodecyl dimethyl betaine, ultrasonically extracted at a power of 150W for 8min, filtered, and filtrate 2 was collected, filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume, and then 500mL of anhydrous ethanol was added to the concentrate for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain blueberry extract.

[0047] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 15g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 30g of 2-aminocinnamic acid, 50g of carboxymethyl gellan gum, and 5g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated at 60°C for reaction for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 90g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 3g of ammonium persulfate is added, and the mixture is heated at 60°C for reaction for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0048] The preparation method of the carboxymethyl gellan gum is as follows:

[0049] At 30°C, 10 g of gellan gum, 60 mL of 3 mol / L sodium hydroxide aqueous solution, and 230 mL of 99 wt% ethanol aqueous solution were mixed and stirred for 30 min; 50 g of monochloroacetic acid was added and stirred for 20 min to obtain a mixed solution; the mixed solution was heated to 60°C and reacted for 12 h; the mixed solution was cooled to 30°C and filtered, the filter cake was dissolved with 5 times the mass of water, and then anhydrous ethanol was added thereto for precipitation, filtered, the filter cake was washed with methanol and dried at 50°C for 12 h to obtain carboxymethyl gellan gum.

[0050] Example 3

[0051] A method for preparing a blueberry whitening and freckle-removing hydrogel patch comprises the following steps:

[0052] S1. 8g of sodium alginate, 5g of gelatin, 1g of calcium chloride, 20g of butylene glycol, 1g of sodium benzoate, 5g of eucalyptus oil, 3g of anhydrous ethanol, 1g of sodium hydroxide, 15g of bilberry extract microcapsules, and 41g of deionized water are mixed evenly and then vacuum degassed to obtain a whitening and freckle-removing liquid. The whitening and freckle-removing liquid is then coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0053] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0054] The preparation method of the bilberry extract is as follows:

[0055] 1200g of choline chloride and 400g of sodium acetate were mixed and stirred at 80°C for 4 hours to obtain a low eutectic solvent, 100g of blueberry stems and leaves were dried, crushed and sieved, and then added to the low eutectic solvent, ultrasonically treated at a power of 150W for 8min, and then heated and extracted at 60°C for 4h, cooled and filtered to separate filtrate 1 and residue, and the residue was added to 1000g of an aqueous solution containing 8wt% dodecyl dimethyl betaine, ultrasonically extracted at a power of 150W for 8min, filtered, and filtrate 2 was collected, filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume, and then 500mL of anhydrous ethanol was added to the concentrate for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain blueberry extract.

[0056] The preparation method of the composite microcapsule is as follows: 90g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 15g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 24g of 2-aminocinnamic acid, 45g of carboxymethyl gellan gum, and 9g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated at 60°C for reaction for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 40g of modified montmorillonite and 80g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 6g of ammonium persulfate is added, and the mixture is heated at 60°C for reaction for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0057] The preparation method of the carboxymethyl gellan gum is as follows:

[0058] At 30°C, 10 g of gellan gum, 60 mL of 3 mol / L sodium hydroxide aqueous solution, and 230 mL of 99 wt% ethanol aqueous solution were mixed and stirred for 30 min; 50 g of monochloroacetic acid was added and stirred for 20 min to obtain a mixed solution; the mixed solution was heated to 60°C and reacted for 12 h; the mixed solution was cooled to 30°C and filtered, the filter cake was dissolved with 5 times the mass of water, and then anhydrous ethanol was added thereto for precipitation, filtered, the filter cake was washed with methanol and dried at 50°C for 12 h to obtain carboxymethyl gellan gum.

[0059] Comparative Example 1

[0060] A method for preparing a blueberry whitening and freckle-removing hydrogel patch is similar to that of Example 1, except that carboxymethyl gellan gum is not added to the composite microcapsule, and specifically comprises the following steps:

[0061] S1. Mix 5g of carbomer 940, 3g of gelatin, 0.5g of aluminum oxide, 13.8g of glycerin, 0.8g of sodium benzoate, 3g of eucalyptus oil, 2g of anhydrous ethanol, 0.5g of sodium hydroxide, 12g of bilberry extract microcapsules, and 59.4g of deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0062] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0063] The preparation method of the bilberry extract is as follows:

[0064] 1200g of choline chloride and 400g of sodium acetate were mixed and stirred at 80°C for 4 hours to obtain a low eutectic solvent, 100g of blueberry stems and leaves were dried, crushed and sieved, and then added to the low eutectic solvent, ultrasonically treated at a power of 150W for 8min, and then heated and extracted at 60°C for 4h, cooled and filtered to separate filtrate 1 and residue, and the residue was added to 1000g of an aqueous solution containing 8wt% dodecyl dimethyl betaine, ultrasonically extracted at a power of 150W for 8min, filtered, and filtrate 2 was collected, filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume, and then 500mL of anhydrous ethanol was added to the concentrate for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain blueberry extract.

[0065] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 16g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 28g of 2-aminocinnamic acid and 8g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated and reacted at 60°C for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 70g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 4g of ammonium persulfate is added, and the mixture is heated and reacted at 60°C for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0066] Comparative Example 2

[0067] A method for preparing a blueberry whitening and freckle-removing hydrogel patch is similar to that of Example 1, except that 2-aminocinnamic acid is not added to the composite microcapsules, and specifically comprises the following steps:

[0068] S1. Mix 5g of carbomer 940, 3g of gelatin, 0.5g of aluminum oxide, 13.8g of glycerin, 0.8g of sodium benzoate, 3g of eucalyptus oil, 2g of anhydrous ethanol, 0.5g of sodium hydroxide, 12g of bilberry extract microcapsules, and 59.4g of deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0069] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of montmorillonite is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0070] The preparation method of the bilberry extract is as follows:

[0071] 1200g of choline chloride and 400g of sodium acetate were mixed and stirred at 80°C for 4 hours to obtain a low eutectic solvent, 100g of blueberry stems and leaves were dried, crushed and sieved, and then added to the low eutectic solvent, ultrasonically treated at a power of 150W for 8min, and then heated and extracted at 60°C for 4h, cooled and filtered to separate filtrate 1 and residue, and the residue was added to 1000g of an aqueous solution containing 8wt% dodecyl dimethyl betaine, ultrasonically extracted at a power of 150W for 8min, filtered, and filtrate 2 was collected, filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume, and then 500mL of anhydrous ethanol was added to the concentrate for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain blueberry extract.

[0072] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 16g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 48g of carboxymethyl gellan gum and 8g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated and reacted at 60°C for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 70g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 4g of ammonium persulfate is added, and the mixture is heated and reacted at 60°C for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0073] Comparative Example 3

[0074] A method for preparing a bilberry whitening and anti-freckle hydrogel patch is similar to that of Example 1, except that the filter residue is directly extracted with water during the extraction of the bilberry extract, and specifically comprises the following steps:

[0075] S1. Mix 5g of carbomer 940, 3g of gelatin, 0.5g of aluminum oxide, 13.8g of glycerin, 0.8g of sodium benzoate, 3g of eucalyptus oil, 2g of anhydrous ethanol, 0.5g of sodium hydroxide, 12g of bilberry extract microcapsules, and 59.4g of deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0076] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0077] The preparation method of the bilberry extract is as follows:

[0078] 1200 g of choline chloride and 400 g of sodium acetate were mixed and stirred at 80° C. for 4 hours to obtain a low eutectic solvent; 100 g of blueberry stems and leaves were dried, crushed, sieved, and added to the low eutectic solvent; the mixture was ultrasonically treated at a power of 150 W for 8 minutes, and then heated and extracted at 60° C. for 4 hours; the filtrate 1 and the residue were separated by cooling and filtration; the residue was added to 1000 g of water, and ultrasonically extracted at a power of 150 W for 8 minutes, and then filtered to collect filtrate 2; filtrate 1 and filtrate 2 were combined, and then concentrated under reduced pressure to 3 / 4 of the original volume; 500 mL of anhydrous ethanol was added to the concentrate for alcohol precipitation, and the precipitate was separated by centrifugation; 500 mL of anhydrous ethanol was added for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain a blueberry extract.

[0079] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 16g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 28g of 2-aminocinnamic acid, 48g of carboxymethyl gellan gum, and 8g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated at 60°C for reaction for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 70g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 4g of ammonium persulfate is added, and the mixture is heated at 60°C for reaction for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0080] The preparation method of the carboxymethyl gellan gum is as follows:

[0081] At 30°C, 10 g of gellan gum, 60 mL of 3 mol / L sodium hydroxide aqueous solution, and 230 mL of 99 wt% ethanol aqueous solution were mixed and stirred for 30 min; 50 g of monochloroacetic acid was added and stirred for 20 min to obtain a mixed solution; the mixed solution was heated to 60°C and reacted for 12 h; the mixed solution was cooled to 30°C and filtered, the filter cake was dissolved with 5 times the mass of water, and then anhydrous ethanol was added thereto for precipitation, filtered, the filter cake was washed with methanol and dried at 50°C for 12 h to obtain carboxymethyl gellan gum.

[0082] Comparative Example 4

[0083] A method for preparing a bilberry whitening and freckle-removing hydrogel patch, the difference being that the bilberry extract is directly extracted with water, comprising the following steps:

[0084] S1. Mix 5g of carbomer 940, 3g of gelatin, 0.5g of aluminum oxide, 13.8g of glycerin, 0.8g of sodium benzoate, 3g of eucalyptus oil, 2g of anhydrous ethanol, 0.5g of sodium hydroxide, 12g of bilberry extract microcapsules, and 59.4g of deionized water, and then degas by vacuum to obtain a whitening and freckle-removing liquid. Then, the whitening and freckle-removing liquid is coated on a non-woven fabric, and then covered with release paper. After curing, it is cut and trimmed to obtain the bilberry whitening and freckle-removing hydrogel patch.

[0085] The preparation method of the bilberry extract microcapsule is as follows: 20 g of bilberry extract is dissolved in 100 mL of deionized water to obtain a bilberry extract aqueous solution, and then 30 g of the composite microcapsule is immersed in the bilberry extract aqueous solution, oscillated at 35° C. for 72 hours, filtered, the solid matter is collected, washed with deionized water, and dried to obtain the bilberry extract microcapsule.

[0086] The preparation method of the bilberry extract is as follows:

[0087] 100 g of blueberry stems and leaves were dried, crushed, sieved, and added to water. After ultrasonic treatment at a power of 150 W for 8 minutes, the extract was heated at 80° C. for extraction for 4 hours. After the extraction was completed, the extract was collected by filtration, and the extract was concentrated to 3 / 4 of the original volume under reduced pressure; then the concentrate was added with 500 mL of anhydrous ethanol for alcohol precipitation, and the precipitate was separated by centrifugation and freeze-dried to obtain the blueberry extract.

[0088] The preparation method of the composite microcapsule is as follows: 100g of montmorillonite is calcined at 300°C for 4h, and then impregnated with a 1mol / L sodium hydroxide aqueous solution for 2h. After the impregnation is completed, the mixture is filtered, washed, dried, and added to 300mL of 50wt% ethanol aqueous solution, 16g of KH550 is added, and the mixture is heated and stirred at 50°C for 2h, filtered, and the solid is collected, washed, dried, and added to 300mL of water, 28g of 2-aminocinnamic acid, 48g of carboxymethyl gellan gum, and 8g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added, the pH value is adjusted to 5, and the mixture is heated at 60°C for reaction for 3h, and the solid is filtered, collected, washed, and dried to obtain modified montmorillonite; 30g of modified montmorillonite and 70g of N-isopropylacrylamide are added to 300mL of anhydrous ethanol, 4g of ammonium persulfate is added, and the mixture is heated at 60°C for reaction for 4h, centrifuged, and the solid is collected, washed, and dried to obtain the composite microcapsule.

[0089] The preparation method of the carboxymethyl gellan gum is as follows:

[0090] At 30°C, 10 g of gellan gum, 60 mL of 3 mol / L sodium hydroxide aqueous solution, and 230 mL of 99 wt% ethanol aqueous solution were mixed and stirred for 30 min; 50 g of monochloroacetic acid was added and stirred for 20 min to obtain a mixed solution; the mixed solution was heated to 60°C and reacted for 12 h; the mixed solution was cooled to 30°C and filtered, the filter cake was dissolved with 5 times the mass of water, and then anhydrous ethanol was added thereto for precipitation, filtered, the filter cake was washed with methanol and dried at 50°C for 12 h to obtain carboxymethyl gellan gum.

[0091] Performance Testing

[0092] Composite microcapsule controlled release test: The test objects are the composite microcapsules prepared in Examples 1-3 and Comparative Examples 1-2. 20 g of VB12 (vitamin B12) is dissolved in 100 mL of deionized water to obtain a VB12 aqueous solution, and then 30 g of the composite microcapsules are immersed in the VB12 aqueous solution, shaken and dialyzed at 35°C for 72 hours, filtered, the solids are collected, washed with deionized water, and dried to obtain VB12 microcapsules; then the VB12 microcapsules are immersed in 100 mL of a 50 wt% methanol aqueous solution at 36.5°C, VB12 will diffuse into methanol as the water and methanol in the gel are exchanged, and the concentration of VB12 in the solution is determined by high performance liquid chromatography, thereby calculating the release of VB12 over time at a human body temperature of 36.5°C; the test results are shown in Table 1:

[0093] Table 1 Composite microcapsule controlled release test results

[0094]

[0095]

[0096] It can be seen from the experimental results in Table 1 that the release rate of the composite microcapsules prepared in Comparative Examples 1 and 2 is significantly faster than that of the composite microcapsules prepared in Examples 1-3. However, too fast a release rate may result in a shorter drug action time, thereby causing drug waste and reducing the therapeutic effect; the composite microcapsules prepared in Examples 1-3 have a relatively moderate release rate and can stably release the drug over a longer period of time, thereby better matching the drug absorption rate.

[0097] Melanin inhibition rate test:

[0098] The whitening and anti-freckle liquid prepared in Examples 1-3 and Comparative Examples 3-4 was added to the DMEM culture medium at a mass concentration of 1%, and sterilized by filtering through a 0.22 μm filter membrane for later use;

[0099] Mouse melanoma B16-F10 cells were cultured at 2×10 5 The cells were inoculated into a 6-well plate at a density of 10 cells / well, incubated at 37°C, 5% CO2 for 48 hours, then the plate was removed, the culture medium in the well was discarded, and PBS was used to wash once, and the DMEM culture medium containing the whitening and freckle removal solution was added. The DMEM culture medium without any active ingredients was used as a blank control, and each well was repeated 3 times, and the culture was continued for 48 hours. After the culture was completed, the cells were lysed, and the intracellular melanin was extracted by centrifugation. 200 μL of 1 mol / L sodium hydroxide solution containing 10% DMSO was added, and then placed in an 80°C water bath for heating for 2.5 hours. After the melanin was completely dissolved, 180 μL was drawn into a 96-well plate, and the absorbance value at 492 nm was detected using an enzyme marker, recorded as the OD value, and the melanin inhibition rate was calculated according to the following formula. The results are shown in Table 2.

[0100] Melanin inhibition rate = [(OD blank group-OD experimental group) / OD blank group] × 100%;

[0101] Table 2 Whitening performance test results

[0102]

[0103]

[0104] It can be seen from the experimental results in Table 2 that the whitening and freckle removal liquid prepared by the present invention has a good effect of inhibiting melanin, reducing the generation of melanin, and achieving the effect of whitening and freckle removal.

[0105] The above are only preferred embodiments of the present invention, and do not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the patent protection scope of the present invention.

Claims

1. A blueberry whitening and freckle-removing hydrogel patch, characterized in that: The invention comprises a backing layer, a matrix layer and an anti-adhesive layer; the backing layer is a non-woven fabric, and the anti-adhesive layer is one of release paper, a polypropylene film and a polyethylene film; the matrix layer is applied on the backing layer, and the anti-adhesive layer is covered on the matrix layer; the matrix layer comprises the following components in percentage by weight: 2-8% of a polymer skeleton material, 1-5% of a viscosity enhancer, 0.1-1% of a cross-linking agent, 10-20% of a moisturizer, 0.5-1% of a preservative, 1-5% of a penetration enhancer, 1-3% of anhydrous ethanol, 0.1-1% of a pH adjuster, 7-15% of a blueberry extract microcapsule, and the remainder is deionized water.

2. The patch according to claim 1, characterized in that The method comprises the following steps: the polymer skeleton material is at least one of carbomer, sodium carboxymethyl cellulose, sodium alginate and sodium hyaluronate.

3. The patch according to claim 1, characterized in that: The viscosity enhancer is at least one of gelatin, carboxymethyl cellulose and polyvinyl pyrrolidone.

4. The patch according to claim 1, characterized in that: The cross-linking agent is at least one of aluminum oxide, alum, calcium chloride and calcium sulfate.

5. The patch according to claim 1, characterized in that: The preparation method of the bilberry extract microcapsule is as follows: dissolving the bilberry extract with deionized water to obtain a bilberry extract aqueous solution, then immersing the composite microcapsule in the bilberry extract aqueous solution for oscillation dialysis, filtering, collecting the solid, washing it with deionized water, and drying it to obtain the bilberry extract microcapsule.

6. The patch according to claim 5, characterized in that The preparation method of the bilberry extract is as follows: The dried, crushed and sieved blueberry stems and leaves are added to a low eutectic solvent, subjected to ultrasonic treatment, and then subjected to heating extraction, cooled, and filtered to separate a filtrate 1 and a filter residue, and the filter residue is added to an aqueous solution containing dodecyl dimethyl betaine, subjected to ultrasonic extraction, filtered, and a filtrate 2 is collected; the filtrate 1 and the filtrate 2 are combined, and then concentrated under reduced pressure, and then ethanol is added to the concentrate for alcohol precipitation, and the precipitate is separated by centrifugation and freeze-dried to obtain a blueberry extract.

7. The patch according to claim 5, characterized in that: The deep eutectic solvent is a mixture of choline chloride and sodium acetate.

8. The patch according to claim 5, characterized in that The preparation method of the composite microcapsule is as follows: calcining montmorillonite and then impregnating it with an alkaline solution, filtering, washing, drying and adding it to an ethanol aqueous solution after the impregnation is completed, adding KH550, heating and stirring, filtering, collecting solids, washing and drying, and adding it to water, adding 2-aminocinnamic acid, carboxymethyl gellan gum, 1-ethyl-(3-dimethylaminopropyl) carbodiimide, adjusting the pH value to acidic, heating to react, filtering, collecting solids, washing and drying to obtain modified montmorillonite; adding the modified montmorillonite and N-isopropylacrylamide to anhydrous ethanol, adding ammonium persulfate, heating to react, centrifuging, collecting solids, washing and drying to obtain the composite microcapsule.

9. The patch according to claim 8, characterized in that: The mass ratio of the montmorillonite, KH550, 2-aminocinnamic acid, carboxymethyl gellan gum, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 20-30:3-5:6-8:10-15:1-3; the mass ratio of the modified montmorillonite, N-isopropylacrylamide, and ammonium persulfate is 1-2:3-4:0.1-0.

3.

10. A method for preparing the patch according to any one of claims 1 to 9, characterized in that: The steps include: The components are weighed according to the formula, and the polymer skeleton material, viscosity enhancer, cross-linking agent, moisturizer, preservative, penetration enhancer, anhydrous ethanol, pH adjuster, bilberry extract microcapsule and deionized water are evenly mixed and then subjected to vacuum degassing to obtain a whitening and freckle-removing liquid, and then the whitening and freckle-removing liquid is coated on a non-woven fabric by a machine, and then covered with an anti-sticking layer, and then cut and trimmed after curing to obtain the bilberry whitening and freckle-removing hydrogel patch.

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