Nicotinamide anti-inflammatory emulsion and preparation method thereof

Abstract

The invention provides a nicotinamide anti-inflammatory emulsion and a preparation method thereof, and belongs to the technical field of cosmetics. The preparation method comprises the following steps: dispersing cranberry seed oil, eucalyptus essential oil, rutin, phytoextraction essence, cetostearyl alcohol and span-80 in shea butter, stirring and dispersing to obtain a first mixture, dispersing nicotinamide sustained-release microspheres in deionized water, stirring and mixing to obtain a second mixture; the first mixture and the second mixture are subjected to a homogeneous reaction, and the nicotinamide anti-inflammatory emulsion is prepared. According to the nicotinamide anti-inflammatory emulsion provided by the invention, a set of multi-dimensional synergistic anti-inflammatory emulsion is constructed by scientifically proportioning the cranberry seed oil, the eucalyptus essential oil, the rutin, the plant extraction essence, the nicotinamide sustained-release microspheres and other active ingredients, and all the components are mutually synergistic and matched, so that the nicotinamide anti-inflammatory emulsion has a good soothing and anti-inflammatory effect, and has a good anti-inflammatory effect. And better protection is provided for skin health.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and specifically relates to a niacinamide anti-inflammatory emulsion and a preparation method thereof. Background Art

[0002] As a B-vitamin substance, niacinamide has high safety. With the increasingly close penetration and combination of cosmetics science and medicine, as well as the strong development of cosmetics science itself, the application fields of niacinamide have been gradually broadened. From the research results and relevant data reports at home and abroad, the application of niacinamide in cosmetics involves whitening products, skin moisturizing and anti-wrinkle products, acne treatment products, hair washing and hair care products, etc. Research shows that niacinamide can make the skin appearance smoother and more uniform, and has six skin care effects: whitening, anti-aging, improving skin barrier function, moisturizing, and treating acne. In addition to the traditional whitening effect, it is also used to reduce the generated and precipitated melanin, block its transfer to the surface cells, accelerate cell metabolism, and accelerate the exfoliation of melanin keratinocytes. However, when niacinamide is directly applied to cosmetics, there are problems of easy discoloration and instability.

[0003] Chinese Patent CN 111803398B discloses an acne pustule composition, a preparation method and an application thereof, which encapsulate seven active components including papain, niacinamide, zinc gluconate, capryloyl glycine, caprylyl glycol, linoleic acid and chitosan oligosaccharide in vesicles, and solve the acne problem from four dimensions of regulating epidermal hyperkeratosis, controlling oil, sterilizing and anti-inflammatory. However, when niacinamide is used in combination with acidic components, chemical reactions may occur, reducing the activity or generating irritating substances; Chinese Patent CN106265247B discloses a preparation method of a multi-effect repair cream, and the skin conditioners therein include materials such as niacinamide, peony extract and bisabolol. However, niacinamide is easily degraded in a weakly acidic environment, while plant extracts such as peony extract require a neutral or weakly alkaline environment to maintain their activity, which may lead to difficult pH adjustment of the formula and accelerate the conversion of niacinamide into nicotinic acid, causing irritation.

[0004] Therefore, providing a new delivery system based on niacinamide stable protection and controlled release technology, while maintaining its anti-inflammatory activity, achieving slow release and enhanced efficiency and reducing skin irritation, has become the key challenge to break through the application limitations of the current niacinamide anti-inflammatory emulsion. Summary of the Invention

[0005] To solve the problems existing in the prior art, the present invention provides a niacinamide anti-inflammatory emulsion and a preparation method thereof. Specifically, the technical solution of the present invention includes the following contents: A preparation method of a niacinamide anti-inflammatory emulsion, the preparation method comprising the following steps: Cranberry seed oil, eucalyptus essential oil, rutin, plant extract essence, cetearyl alcohol, and span - 80 are dispersed in shea butter and stirred to obtain a first mixture. Nicotinamide sustained - release microspheres are dispersed in deionized water and stirred to obtain a second mixture. The first mixture and the second mixture are homogenized to prepare a nicotinamide anti - inflammatory emulsion.

[0006] Furthermore, the preparation method of the nicotinamide sustained - release microspheres includes the following steps: β - cyclodextrin, sodium periodate, and ethylene glycol are stirred and reacted to obtain modified β - cyclodextrin. Salicylic acid, 1 - ethyl - 3 - (3 - dimethylaminopropyl) carbodiimide, N - hydroxysuccinimide, and ethylenediamine are stirred and reacted to obtain amino - modified salicylic acid. Nicotinamide and cinnamoyl chloride are stirred and reacted to obtain modified nicotinamide. The modified nicotinamide and the modified β - cyclodextrin are stirred and reacted to obtain a nicotinamide complex. The amino - modified salicylic acid and the nicotinamide complex are stirred and reacted to prepare the nicotinamide sustained - release microspheres.

[0007] Furthermore, the preparation of the plant extract essence includes the following steps: Broccoli is chopped to obtain broccoli granules. Ascorbic acid and calcium chloride are dispersed in a citrate - phosphate buffer solution to obtain an activation solution. The broccoli granules are dispersed in the activation solution and successively subjected to stirring reaction, ultrasonic extraction, and filtration to obtain a filtrate. The filtrate is successively subjected to rotary evaporation, extraction, purification, and drying to prepare the plant extract essence.

[0008] Furthermore, the weight ratio of the β - cyclodextrin, sodium periodate, and ethylene glycol is 1 - 1.5:0.45 - 0.55:0.5 - 1.

[0009] Furthermore, the weight ratio of the salicylic acid, 1 - ethyl - 3 - (3 - dimethylaminopropyl) carbodiimide, N - hydroxysuccinimide, and ethylenediamine is 1 - 2:1 - 1.3:0.7 - 0.8:0.5 - 0.8.

[0010] Furthermore, the weight ratio of the nicotinamide and cinnamoyl chloride is 1 - 2:3 - 6.

[0011] Furthermore, the stirring reaction of the nicotinamide and cinnamoyl chloride includes a reaction temperature of 23 - 25 °C and a reaction time of 3 - 4 h.

[0012] Furthermore, the weight ratio of the modified nicotinamide and the modified β - cyclodextrin is 1 - 2:2 - 4.

[0013] Furthermore, the stirring reaction of the modified nicotinamide and the modified β - cyclodextrin includes a reaction temperature of 25 - 30 °C and a reaction time of 1 - 2 h.

[0014] Furthermore, the weight ratio of the amino - modified salicylic acid and the nicotinamide complex is 1.5 - 2:1.8 - 2.2.

[0015] Furthermore, the stirring reaction of the amidated salicylic acid and niacinamide complex includes a reaction temperature of 25 to 37 °C and a reaction time of 12 to 24 h.

[0016] Furthermore, the size of the broccoli granules is 2 to 3 mm.

[0017] Furthermore, the weight ratio of ascorbic acid, calcium chloride, and citrate-phosphate buffer is 0.4 to 0.5: 0.04 to 0.05: 200.

[0018] Furthermore, the ultrasonic extraction includes an extraction temperature of 40 to 50 °C and an extraction time of 20 to 30 min.

[0019] Furthermore, the weight ratio of cranberry seed oil, eucalyptus essential oil, rutin, plant extract essence, cetearyl alcohol, span-80, and shea butter is 0.3 to 0.5: 0.3 to 0.5: 0.3 to 0.5: 0.1 to 0.5: 1.5 to 2.5: 1.5 to 2.5: 8 to 16.

[0020] Furthermore, the stirring and dispersion include a stirring temperature of 50 to 60 °C and a stirring time of 20 to 30 min.

[0021] Furthermore, the weight ratio of the niacinamide sustained-release microspheres and deionized water is 1 to 3: 70 to 80.

[0022] Furthermore, the stirring and mixing include a stirring temperature of 50 to 60 °C and a stirring time of 20 to 30 min.

[0023] Furthermore, the weight ratio of the first mixture and the second mixture is 1 to 1.2: 1.

[0024] Furthermore, the homogenization reaction is to homogenize at 50 to 60 °C for 10 to 15 min, then cool down to 40 to 45 °C, adjust the pH to 5.5 to 6.5, and homogenize again for 3 to 5 min.

[0025] Furthermore, the homogenization speed of the homogenization reaction is 2000 to 3000 r / min.

[0026] Furthermore, when the niacinamide anti-inflammatory emulsion prepared by the present invention is used, first thinly apply 0.5% salicylic acid on the skin surface for 2 to 3 min, and then apply the niacinamide anti-inflammatory emulsion of the present invention.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) In the present invention, β-cyclodextrin is subjected to an oxidation reaction to obtain modified β-cyclodextrin, salicylic acid and ethylenediamine are subjected to an amide reaction to obtain aminosalicylic acid, cinnamoyl chloride is subjected to an N-alkylation reaction to modify nicotinamide so that the modified nicotinamide has hydrophobicity, and the modified nicotinamide is encapsulated in the hydrophobic cavity of the modified β-cyclodextrin through hydrophobic interaction to obtain a nicotinamide complex, and the aminosalicylic acid and nicotinamide complex are subjected to a Schiff base reaction to obtain nicotinamide sustained-release microspheres; the nicotinamide sustained-release microspheres have pH responsiveness and can achieve intelligent targeted release of nicotinamide; in addition, the hydrophobic chain of the modified nicotinamide and the β-cyclodextrin cavity form a dynamic equilibrium release system, which maintains the long-term sustained release of nicotinamide on the skin surface, continuously inhibits pro-inflammatory factors, and avoids fluctuations in the anti-inflammatory effect caused by rapid metabolism.

[0028] (2) The present invention utilizes the myrosinase of broccoli to extract plant extract essence, adds antioxidant blood acid to protect the enzyme active center to prevent oxidative inactivation, adds calcium chloride to provide calcium ions to stabilize the enzyme structure, enhances catalytic efficiency, reduces dependence on exogenous reagents, and rationally utilizes endogenous enzymes to extract plant extract essence; the plant extract essence extracted by the present invention can protect the skin from oxidative stress damage in the niacinamide anti-inflammatory emulsion, maintain the skin in a healthy state, and relieve skin discomfort.

[0029] (3) The cranberry seed oil and eucalyptus essential oil in the present invention can cooperate with niacinamide to exert a synergistic effect to enhance the anti-inflammatory effect; rutin helps to reduce the irritation of other components in the niacinamide anti-inflammatory emulsion to the skin, helps to enhance the integrity of the skin barrier, enables the skin to better resist external stimuli, and reduces skin discomfort and inflammation caused by external factors.

[0030] (4) The niacinamide anti-inflammatory emulsion provided by the present invention is a multi-dimensional synergistic anti-inflammatory emulsion constructed by scientifically proportioning active ingredients such as cranberry seed oil, eucalyptus essential oil, rutin, plant extract essence and niacinamide sustained-release microspheres. The components work together and cooperate with each other, so that the niacinamide anti-inflammatory emulsion has good soothing and anti-inflammatory effects, providing better protection for skin health. DETAILED DESCRIPTION

[0031] The technical solution of the present invention will be clearly and completely described below through the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0032] Unless otherwise specified, the raw materials and reagents used in the present invention are commercially available or can be prepared by known methods.

[0033] Preparation Example 1: Preparation method of nicotinamide sustained-release microspheres, comprising the following steps: 1 part by weight of β-cyclodextrin is dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 10 min, 0.45 part by weight of sodium periodate is added. After stirring and reacting at 23 °C for 2 h in a light-shielded environment, 0.5 part by weight of ethylene glycol is added and stirring and reacting continues for 1 h. After the reaction ends, dialysis is carried out in deionized water using a dialysis bag for 72 h, and then freeze-dried to obtain modified β-cyclodextrin; 1 part by weight of salicylic acid, 1 part by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and 0.7 part by weight of N-hydroxysuccinimide are dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred and activated at 23 °C for 30 min. After the activation ends, 0.5 part by weight of ethylenediamine is added, and the pH is adjusted to 7.0. Stirring and reacting is carried out at 23 °C for 12 h. After the reaction ends, the pH is adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution is dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 1 part by weight of nicotinamide is dispersed in 50 parts by weight of anhydrous tetrahydrofuran. In an environment of 0 °C, 3 parts by weight of cinnamoyl chloride and 1 part by weight of pyridine are added. After stirring and reacting at 23 °C for 3 h, 30 parts by weight of a 5% hydrochloric acid solution by mass is added. After shaking for 1 min, it is allowed to stand for layering. The lower acid layer is discarded, and the upper organic phase is collected and washed several times until the pH of the aqueous phase is 5. 5 parts by weight of anhydrous sodium sulfate is added to the upper organic phase. After stirring and reacting for 15 min, filtration is carried out to obtain a filtrate. The filtrate is rotary-evaporated to remove tetrahydrofuran to obtain a crude product. The crude product is purified by silica gel column chromatography and then vacuum-dried to obtain modified nicotinamide; 1 part by weight of modified nicotinamide and 2 parts by weight of modified β-cyclodextrin are dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水 = 1:4), the pH is adjusted to 6.5, and then stirring and reacting is carried out at 25 °C for 1 h. After the reaction ends, it is successively filtered, centrifuged, and vacuum-dried to obtain a nicotinamide complex; 1.5 parts by weight of amino-functionalized salicylic acid and 1.8 parts by weight of the nicotinamide complex are dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 10 min, stirring and reacting is carried out at 25 °C in the dark for 12 h. After the reaction ends, dialysis is carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to prepare nicotinamide sustained-release microspheres.

[0034] Preparation Example 2: Preparation method of nicotinamide sustained-release microspheres, comprising the following steps: 1.1 parts by weight of β-cyclodextrin was dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 11 min, 0.47 parts by weight of sodium periodate was added. After stirring and reacting for 2.2 h at 24 °C in a light-shielded environment, 0.6 parts by weight of ethylene glycol was added and stirring and reacting continued for 1.2 h. After the reaction ended, dialysis was carried out in deionized water using a dialysis bag for 72 h, and then freeze-dried to obtain modified β-cyclodextrin; 1.2 parts by weight of salicylic acid, 1.1 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.72 parts by weight of N-hydroxysuccinimide were dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred and activated at 24 °C for 32 min. After the activation ended, 0.55 parts by weight of ethylenediamine was added, and the pH was adjusted to 7.1. Stirring and reacting was carried out at 24 °C for 13 h. After the reaction ended, the pH was adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution was dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 1.2 parts by weight of nicotinamide was dispersed in 50 parts by weight of anhydrous tetrahydrofuran. At 1 °C, 3.5 parts by weight of cinnamoyl chloride and 1.1 parts by weight of pyridine were added. Stirring and reacting was carried out at 24 °C for 3.2 h. After the reaction ended, 30 parts by weight of a 5% hydrochloric acid solution was added, and after shaking for 1 min, it was allowed to stand and layer. The lower acid layer was discarded, and the upper organic phase was collected and washed several times until the pH of the aqueous phase was 5.2. 5 parts by weight of anhydrous sodium sulfate was added to the upper organic phase, and after stirring and reacting for 15 min, filtration was carried out to obtain a filtrate. The filtrate was rotary evaporated to remove tetrahydrofuran to obtain a crude product. The crude product was purified by silica gel column chromatography and then vacuum dried to obtain modified nicotinamide; 1.2 parts by weight of modified nicotinamide and 2.5 parts by weight of modified β-cyclodextrin were dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 :V 去离子水 = 1:4). After adjusting the pH to 6.8, stirring and reacting was carried out at 26 °C for 1.5 h. After the reaction ended, filtration, centrifugation and vacuum drying were carried out in sequence to obtain a nicotinamide complex; 1.6 parts by weight of amino-functionalized salicylic acid and 1.9 parts by weight of nicotinamide complex were dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 11 min, stirring and reacting was carried out at 28 °C in the dark for 16 h. After the reaction ended, dialysis was carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to prepare nicotinamide sustained-release microspheres.

[0035] Preparation Example 3: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 1.2 parts by weight of β-cyclodextrin is dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 12 min, 0.49 parts by weight of sodium periodate is added. After stirring and reacting for 2.6 h at 24 °C in a light-shielded environment, 0.7 parts by weight of ethylene glycol is added and the stirring reaction continues for 1.6 h. After the reaction is completed, dialysis is carried out in deionized water using a dialysis bag for 72 h, and then freeze-drying is carried out to obtain modified β-cyclodextrin; 1.6 parts by weight of salicylic acid, 1.2 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.75 parts by weight of N-hydroxysuccinimide are dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred and activated at 24 °C for 36 min. After the activation is completed, 0.6 parts by weight of ethylenediamine is added, and the pH is adjusted to 7.2. The stirring reaction is carried out at 25 °C for 16 h. After the reaction is completed, the pH is adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution is dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 1.5 parts by weight of nicotinamide is dispersed in 50 parts by weight of anhydrous tetrahydrofuran. In an environment of 2 °C, 4.5 parts by weight of cinnamoyl chloride and 1.2 parts by weight of pyridine are added. The stirring reaction is carried out at 25 °C for 3.4 h. After the reaction is completed, 30 parts by weight of a 5% dilute hydrochloric acid solution by mass is added, shaken for 1 min and then allowed to stand for phase separation. The lower acid solution is discarded, and the upper organic phase is collected and washed several times until the pH of the aqueous phase is 5.5. 5 parts by weight of anhydrous sodium sulfate is added to the upper organic phase, and after stirring and reacting for 15 min, filtration is carried out to obtain a filtrate. The filtrate is rotary-evaporated to remove tetrahydrofuran to obtain a crude product. The crude product is purified by silica gel column chromatography and then vacuum-dried to obtain modified nicotinamide; 1.5 parts by weight of modified nicotinamide and 3 parts by weight of modified β-cyclodextrin are dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水 = 1:4), the pH is adjusted to 7, and the stirring reaction is carried out at 25 - 30 °C for 1.5 h. After the reaction is completed, filtration, centrifugation and vacuum drying are carried out in sequence to obtain a nicotinamide complex; 1.7 parts by weight of amino-functionalized salicylic acid and 2.0 parts by weight of the nicotinamide complex are dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 13 min, the stirring reaction is carried out at 32 °C in the dark for 20 h. After the reaction is completed, dialysis is carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-drying is carried out to prepare nicotinamide sustained-release microspheres.

[0036] Preparation Example 4: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 1.4 parts by weight of β-cyclodextrin was dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 13 min, 0.53 parts by weight of sodium periodate was added. After stirring and reacting at 25 °C in a light-shielded environment for 3 h, 0.9 parts by weight of ethylene glycol was added and stirring and reacting continued for 1.8 h. After the reaction ended, dialysis was carried out in deionized water using a dialysis bag for 72 h, and then freeze-dried to obtain modified β-cyclodextrin; 1.8 parts by weight of salicylic acid, 1.3 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.8 parts by weight of N-hydroxysuccinimide were dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred and activated at 25 °C for 40 min. After the activation ended, 0.7 parts by weight of ethylenediamine was added, and the pH was adjusted to 7.0. Stirring and reacting was carried out at 245 °C for 16 h. After the reaction ended, the pH was adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution was dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 1.8 parts by weight of nicotinamide was dispersed in 50 parts by weight of anhydrous tetrahydrofuran. In an environment of 3 °C, 5 parts by weight of cinnamoyl chloride and 1.4 parts by weight of pyridine were added. Stirring and reacting was carried out at 25 °C for 3.8 h. After the reaction ended, 30 parts by weight of a 5% dilute hydrochloric acid solution was added, shaken for 1 min and then allowed to stand for layer separation. The lower acid solution was discarded, and the upper organic phase was collected and washed several times until the pH of the aqueous phase was 6. 5 parts by weight of anhydrous sodium sulfate was added to the upper organic phase, stirred and reacted for 15 min and then filtered to obtain a filtrate. The filtrate was rotary-evaporated to remove tetrahydrofuran to obtain a crude product. The crude product was purified by silica gel column chromatography and then vacuum-dried to obtain modified nicotinamide; 1.8 parts by weight of modified nicotinamide and 4 parts by weight of modified β-cyclodextrin were dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水 = 1:4), the pH was adjusted to 7.5 and then stirred and reacted at 30 °C for 2 h. After the reaction ended, filtration, centrifugation and vacuum drying were carried out in sequence to obtain a nicotinamide complex; 1.8 parts by weight of amino-functionalized salicylic acid and 2.1 parts by weight of the nicotinamide complex were dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 14 min, stirring and reacting was carried out at 35 °C in the dark for 20 h. After the reaction ended, dialysis was carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to prepare nicotinamide sustained-release microspheres.

[0037] Preparation Example 5: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 1.5 parts by weight of β-cyclodextrin was dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 15 min, 0.55 parts by weight of sodium periodate was added. After stirring and reacting at 25 °C for 3 h in a light-proof environment, 1 part by weight of ethylene glycol was added and stirring and reacting continued for 2 h. After the reaction, dialysis was carried out in deionized water using a dialysis bag for 72 h, and then freeze-dried to obtain modified β-cyclodextrin; 2 parts by weight of salicylic acid, 1.3 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.8 parts by weight of N-hydroxysuccinimide were dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with pH 6.0 and stirred and activated at 25 °C for 40 min. After the activation, 0.8 parts by weight of ethylenediamine was added, and the pH was adjusted to 7.5. Stirring and reacting was carried out at 25 °C for 18 h. After the reaction, the pH was adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution was dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 2 parts by weight of nicotinamide was dispersed in 50 parts by weight of anhydrous tetrahydrofuran. In an environment of 0 °C, 6 parts by weight of cinnamoyl chloride and 1.5 parts by weight of pyridine were added. Stirring and reacting was carried out at 25 °C for 4 h. After the reaction, 30 parts by weight of a 5% hydrochloric acid solution by mass was added, shaken for 1 min and then allowed to stand for layering. The lower acid layer was discarded, and the upper organic phase was collected and washed several times until the pH of the aqueous phase was 6. 5 parts by weight of anhydrous sodium sulfate was added to the upper organic phase, stirred and reacted for 15 min and then filtered to obtain a filtrate. The filtrate was rotary evaporated to remove tetrahydrofuran to obtain a crude product. The crude product was purified by silica gel column chromatography and then vacuum dried to obtain modified nicotinamide; 2 parts by weight of modified nicotinamide and 4 parts by weight of modified β-cyclodextrin were dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水 = 1:4), the pH was adjusted to 7.5 and then stirred and reacted at 30 °C for 2 h. After the reaction, filtration, centrifugation and vacuum drying were carried out in sequence to obtain a nicotinamide complex; 2 parts by weight of amino-functionalized salicylic acid and 2.2 parts by weight of nicotinamide complex were dispersed in 20 parts by weight of PBS buffer solution with pH 6.0. After ultrasonic dispersion for 15 min, stirring and reacting was carried out at 37 °C in the dark for 24 h. After the reaction, dialysis was carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to prepare nicotinamide sustained-release microspheres.

[0038] Preparation Example 6: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 1.5 parts by weight of γ-cyclodextrin was dispersed in 100 parts by weight of deionized water. After ultrasonic dispersion for 15 min, 0.55 parts by weight of sodium periodate was added. After stirring and reacting at 25 °C for 3 h in a light-proof environment, 1 part by weight of ethylene glycol was added and stirring and reacting continued for 2 h. After the reaction ended, dialysis was carried out in deionized water using a dialysis bag for 72 h, and then freeze-dried to obtain modified β-cyclodextrin; 2 parts by weight of salicylic acid, 1.3 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.8 parts by weight of N-hydroxysuccinimide were dispersed in 2-(N-morpholino)ethanesulfonic acid buffer solution with a pH of 6.0 and stirred and activated at 25 °C for 40 min. After the activation ended, 0.8 parts by weight of ethylenediamine was added, and the pH was adjusted to 7.5, and stirred and reacted at 25 °C for 18 h. After the reaction ended, the pH was adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution was dialyzed in deionized water using a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 2 parts by weight of nicotinamide was dispersed in 50 parts by weight of anhydrous tetrahydrofuran. In an environment of 0 °C, 6 parts by weight of cinnamoyl chloride and 1.5 parts by weight of pyridine were added, and stirred and reacted at 25 °C for 4 h. After the reaction ended, 30 parts by weight of a 5% hydrochloric acid solution was added, shaken for 1 min and then allowed to stand for layer separation. The lower acid layer was discarded, and the upper organic phase was washed several times until the pH of the aqueous phase was 6. 5 parts by weight of anhydrous sodium sulfate was added to the upper organic phase, stirred and reacted for 15 min and then filtered to obtain a filtrate. The filtrate was rotary evaporated to remove tetrahydrofuran to obtain a crude product. The crude product was purified by silica gel column chromatography and then vacuum dried to obtain modified nicotinamide; 2 parts by weight of modified nicotinamide and 4 parts by weight of modified β-cyclodextrin were dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 :V 去离子水 = 1:4), adjusted the pH to 7.5 and then stirred and reacted at 30 °C for 2 h. After the reaction ended, it was successively filtered, centrifuged and vacuum dried to obtain a nicotinamide complex; 2 parts by weight of amino-functionalized salicylic acid and 2.2 parts by weight of nicotinamide complex were dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 15 min, stirred and reacted at 37 °C in the dark for 24 h. After the reaction ended, dialysis was carried out in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to prepare nicotinamide sustained-release microspheres.

[0039] Preparation Example 7: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 2 parts by weight of salicylic acid, 1.3 parts by weight of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.8 parts by weight of N-hydroxysuccinimide are dispersed in 2-morpholinoethanesulfonic acid buffer solution with a pH of 6.0, stirred and activated at 25°C for 40 min. After the activation is completed, 0.8 parts by weight of ethylenediamine is added, and the pH is adjusted to 7.5. The mixture is stirred and reacted at 25°C for 18 h. After the reaction is completed, the pH is adjusted to 5.0 to terminate the reaction to obtain a reaction solution. The reaction solution is dialyzed in deionized water with a dialysis bag for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain amino-functionalized salicylic acid; 2 parts by weight of nicotinamide is dispersed in 50 parts by weight of anhydrous tetrahydrofuran. At 0°C, 6 parts by weight of cinnamoyl chloride and 1.5 parts by weight of pyridine are added, and the mixture is stirred and reacted at 25°C for 4 h. After the reaction is completed, 30 parts by weight of a 5% hydrochloric acid solution by mass is added, shaken for 1 min and then allowed to stand for phase separation. The lower acid solution is discarded, and the upper organic phase is collected and washed several times until the pH of the aqueous phase is 6. 5 parts by weight of anhydrous sodium sulfate is added to the upper organic phase, stirred and reacted for 15 min, and then filtered to obtain a filtrate. The filtrate is rotary-evaporated to remove tetrahydrofuran to obtain a crude product. The crude product is purified by silica gel column chromatography and then vacuum-dried to obtain modified nicotinamide; 2 parts by weight of modified nicotinamide and 4 parts by weight of β-cyclodextrin are dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水 = 1:4), the pH is adjusted to 7.5, and the mixture is stirred and reacted at 30°C for 2 h. After the reaction is completed, it is successively filtered, centrifuged and vacuum-dried to obtain a nicotinamide complex; 2 parts by weight of amino-functionalized salicylic acid and 2.2 parts by weight of nicotinamide complex are dispersed in 20 parts by weight of PBS buffer solution with a pH of 6.0. After ultrasonic dispersion for 15 min, the mixture is stirred and reacted at 37°C in the dark for 24 h. After the reaction is completed, it is dialyzed in deionized water for 72 h to remove by-products and unreacted reagents, and then freeze-dried to obtain nicotinamide sustained-release microspheres.

[0040] Preparation Example 8: A method for preparing nicotinamide sustained-release microspheres, comprising the following steps: 2 parts by weight of nicotinamide is dispersed in 50 parts by weight of anhydrous tetrahydrofuran. At 0°C, 6 parts by weight of cinnamoyl chloride and 1.5 parts by weight of pyridine are added, and the mixture is stirred and reacted at 25°C for 4 h. After the reaction is completed, 30 parts by weight of a 5% hydrochloric acid solution by mass is added, shaken for 1 min and then allowed to stand for phase separation. The lower acid solution is discarded, and the upper organic phase is collected and washed several times until the pH of the aqueous phase is 6. 5 parts by weight of anhydrous sodium sulfate is added to the upper organic phase, stirred and reacted for 15 min, and then filtered to obtain a filtrate. The filtrate is rotary-evaporated to remove tetrahydrofuran to obtain a crude product. The crude product is purified by silica gel column chromatography and then vacuum-dried to obtain modified nicotinamide; 2 parts by weight of modified nicotinamide and 4 parts by weight of β-cyclodextrin are dispersed in 50 parts by weight of a mixed solvent (V 无水乙醇 : V 去离子水=1:4), adjust the pH to 7.5, stir and react at 30 °C for 2 h. After the reaction, filter, centrifuge and vacuum dry in sequence to obtain the nicotinamide sustained-release microspheres.

[0041] Preparation Example 9: The preparation method of the plant extraction essence comprises the following steps: Wash the broccoli and cut it into pieces with a size of 2 mm to obtain broccoli particles; disperse 0.4 parts by weight of ascorbic acid and 0.04 parts by weight of calcium chloride in 200 parts by weight of citric acid-phosphate buffer solution with a pH of 6.0 to obtain an activation solution. Disperse 100 parts by weight of broccoli particles in the above activation solution, stir and react at 40 °C for 1 h, adjust the pH to 4.0 with acetic acid, continue to stir and react at 40 °C for 2 h. After the reaction, add 200 parts by weight of ethanol solution with a volume fraction of 30%, carry out ultrasonic extraction at 40 °C for 20 min. After the ultrasonic extraction, filter with a Buchner funnel, collect the filtrate, and rotary evaporate the filtrate at 60 °C and a vacuum degree of 0.08 MPa for 2 h to obtain a concentrated solution; the concentrated solution is successively subjected to ethyl acetate extraction, column chromatography purification and concentration and drying to obtain the plant extraction essence.

[0042] Preparation Example 10: The preparation method of the plant extraction essence comprises the following steps: Wash the broccoli and cut it into pieces with a size of 2.5 mm to obtain broccoli particles; disperse 0.45 parts by weight of ascorbic acid and 0.045 parts by weight of calcium chloride in 200 parts by weight of citric acid-phosphate buffer solution with a pH of 6.0 to obtain an activation solution. Disperse 100 parts by weight of broccoli particles in the above activation solution, stir and react at 45 °C for 1.5 h, adjust the pH to 4.2 with acetic acid, continue to stir and react at 45 °C for 2.5 h. After the reaction, add 200 parts by weight of ethanol solution with a volume fraction of 30%, carry out ultrasonic extraction at 45 °C for 25 min. After the ultrasonic extraction, filter with a Buchner funnel, collect the filtrate, and rotary evaporate the filtrate at 60 °C and a vacuum degree of 0.08 MPa for 2.5 h to obtain a concentrated solution; the concentrated solution is successively subjected to ethyl acetate extraction, column chromatography purification and concentration and drying to obtain the plant extraction essence.

[0043] Preparation Example 11: The preparation method of the plant extraction essence comprises the following steps: Wash the broccoli and cut it into pieces with a size of 3 mm to obtain broccoli particle; 0.5 parts by weight of ascorbic acid and 0.05 parts by weight of calcium chloride are dispersed in 200 parts by weight of citric acid-phosphate buffer solution with pH 6.0 to obtain an activation solution. 100 parts by weight of broccoli particle are dispersed in the above activation solution, stirred and reacted at 50 °C for 2 h, then the pH is adjusted to 4.5 with acetic acid, and the stirring and reaction are continued at 50 °C for 3 h. After the reaction is completed, 200 parts by weight of ethanol solution with a volume fraction of 30% is added, ultrasonic extraction is carried out at 50 °C for 30 min, and after the ultrasonic treatment, suction filtration is carried out with a Buchner funnel, and the filtrate is collected. The filtrate is rotary evaporated at 60 °C and under a vacuum of 0.08 MPa for 3 h to obtain a concentrated solution; the concentrated solution is successively subjected to ethyl acetate extraction, column chromatography purification and concentration and drying to obtain a plant extraction essence.

[0044] Preparation Example 12: The preparation method of the plant extraction essence comprises the following steps: Wash the broccoli and cut it into pieces with a size of 3 mm to obtain broccoli particle; 100 parts by weight of broccoli particle are dispersed in 200 parts by weight of citric acid-phosphate buffer solution with pH 6.0, stirred and reacted at 50 °C for 2 h, then the pH is adjusted to 4.5 with acetic acid, and the stirring and reaction are continued at 50 °C for 3 h. After the reaction is completed, 200 parts by weight of ethanol solution with a volume fraction of 30% is added, ultrasonic extraction is carried out at 50 °C for 30 min, and after the ultrasonic treatment, suction filtration is carried out with a Buchner funnel, and the filtrate is collected. The filtrate is rotary evaporated at 60 °C and under a vacuum of 0.08 MPa for 3 h to obtain a concentrated solution; the concentrated solution is successively subjected to ethyl acetate extraction, column chromatography purification and concentration and drying to obtain a plant extraction essence.

[0045] Example 1: A preparation method of a niacinamide anti-inflammatory emulsion comprises the following steps: 0.3 parts by weight of cranberry seed oil, 0.3 parts by weight of eucalyptus essential oil, 0.3 parts by weight of rutin, 0.1 part by weight of the plant extraction essence prepared in Preparation Example 9, 1.5 parts by weight of cetearyl alcohol and 1.5 parts by weight of span-80 are dispersed in 8 parts by weight of shea butter and stirred and dispersed at 50 °C for 20 min to obtain a first mixture; 1 part by weight of the niacinamide sustained-release microspheres prepared in Preparation Example 1 is dispersed in 70 parts by weight of deionized water and stirred and mixed at 50 °C for 20 min to obtain a second mixture; 10 parts by weight of the first mixture and 10 parts by weight of the second mixture are homogenized at 50 °C at a rotation speed of 2000 r / min for 10 min and then cooled to 40 °C, and the pH is adjusted to 5.5 with ethanolamine and homogenized again for 3 min to obtain the niacinamide anti-inflammatory emulsion.

[0046] Example 2: A preparation method of a niacinamide anti-inflammatory emulsion comprises the following steps: 0.35 parts by weight of cranberry seed oil, 0.35 parts by weight of eucalyptus essential oil, 0.35 parts by weight of rutin, 0.2 parts by weight of the plant extract obtained in Preparation Example 10, 1.8 parts by weight of cetearyl alcohol and 1.7 parts by weight of span-80 were dispersed in 10 parts by weight of shea butter and stirred and dispersed at 52 °C for 22 min to obtain a first mixture; 1.5 parts by weight of the nicotinamide sustained-release microspheres obtained in Preparation Example 2 were dispersed in 72 parts by weight of deionized water and stirred and mixed at 52 °C for 25 min to obtain a second mixture; 11 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 55 °C at a speed of 2500 r / min for 12 min and then cooled to 42 °C, and the pH was adjusted to 6 with ethanolamine and homogenized again for 4 min to prepare a nicotinamide anti-inflammatory emulsion.

[0047] Example 3: A method for preparing a nicotinamide anti-inflammatory emulsion, comprising the following steps: 0.4 parts by weight of cranberry seed oil, 0.4 parts by weight of eucalyptus essential oil, 0.4 parts by weight of rutin, 0.3 parts by weight of the plant extract obtained in Preparation Example 11, 2 parts by weight of cetearyl alcohol and 2 parts by weight of span-80 were dispersed in 12 parts by weight of shea butter and stirred and dispersed at 55 °C for 25 min to obtain a first mixture; 2.5 parts by weight of the nicotinamide sustained-release microspheres obtained in Preparation Example 3 were dispersed in 75 parts by weight of deionized water and stirred and mixed at 55 °C for 27 min to obtain a second mixture; 11 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 55 °C at a speed of 2500 r / min for 13 min and then cooled to 42 °C, and the pH was adjusted to 6 with ethanolamine and homogenized again for 4 min to prepare a nicotinamide anti-inflammatory emulsion.

[0048] Example 4: A method for preparing a nicotinamide anti-inflammatory emulsion, comprising the following steps: 0.45 parts by weight of cranberry seed oil, 0.45 parts by weight of eucalyptus essential oil, 0.45 parts by weight of rutin, 0.4 parts by weight of the plant extract obtained in Preparation Example 11, 2.2 parts by weight of cetearyl alcohol and 2.2 parts by weight of span-80 were dispersed in 14 parts by weight of shea butter and stirred and dispersed at 58 °C for 28 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained-release microspheres obtained in Preparation Example 4 were dispersed in 78 parts by weight of deionized water and stirred and mixed at 56 °C for 24 min to obtain a second mixture; 11.5 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min and then cooled to 40 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare a nicotinamide anti-inflammatory emulsion.

[0049] Example 5: A method for preparing a nicotinamide anti-inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60°C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres prepared in Preparation Example 5 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60°C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60°C at a speed of 3000 r / min for 15 min, then cooled to 45°C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0050] Comparative Example 1: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60°C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres prepared in Preparation Example 6 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60°C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60°C at a speed of 3000 r / min for 15 min, then cooled to 45°C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0051] Comparative Example 2: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60°C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres prepared in Preparation Example 7 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60°C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60°C at a speed of 3000 r / min for 15 min, then cooled to 45°C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0052] Comparative Example 3: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres prepared in Preparation Example 8 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0053] Comparative Example 5: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 1 part by weight of nicotinamide was dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0054] Comparative Example 6: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract essence prepared in Preparation Example 12, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres prepared in Preparation Example 5 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare the nicotinamide anti - inflammatory emulsion.

[0055] Comparative Example 7: A method for preparing a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of the plant extract obtained in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres obtained in Preparation Example 9 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare a nicotinamide anti - inflammatory emulsion.

[0056] Comparative Example 8: A preparation method of a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of cranberry seed oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract obtained in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres obtained in Preparation Example 9 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare a nicotinamide anti - inflammatory emulsion.

[0057] Comparative Example 9: A preparation method of a nicotinamide anti - inflammatory emulsion, comprising the following steps: 0.5 parts by weight of eucalyptus essential oil, 0.5 parts by weight of rutin, 0.5 parts by weight of the plant extract obtained in Preparation Example 11, 2.5 parts by weight of cetearyl alcohol and 2.5 parts by weight of span - 80 were dispersed in 16 parts by weight of shea butter and stirred and dispersed at 60 °C for 30 min to obtain a first mixture; 3 parts by weight of the nicotinamide sustained - release microspheres obtained in Preparation Example 9 were dispersed in 80 parts by weight of deionized water and stirred and mixed at 60 °C for 30 min to obtain a second mixture; 12 parts by weight of the first mixture and 10 parts by weight of the second mixture were homogenized at 60 °C at a speed of 3000 r / min for 15 min, then cooled to 45 °C, and the pH was adjusted to 6.5 with ethanolamine and homogenized again for 5 min to prepare a nicotinamide anti - inflammatory emulsion.

[0058] Test Example 1: Safety performance test According to the "Technical Specifications for Cosmetics Safety" (2015 Edition), the skin irritation of the nicotinamide anti - inflammatory emulsion was tested to evaluate the safety of the nicotinamide anti - inflammatory emulsion when used on the skin.

[0059] Test samples: Nicotinamide anti-inflammatory emulsions prepared in Examples 1-5 and Comparative Examples 1-9; Test procedure: Select 56 rabbits, randomly divide them into 14 groups with 4 rabbits in each group, and use a test sample. 24 hours before the test, cut the hair on both sides of the spine on the back of the rabbits without damaging the epidermis. The shaved area is 3 cm × 3 cm, which serves as the test area. Apply approximately 0.5 g of the test sample directly on the test area, then cover it with two layers of gauze (2.5 cm × 2.5 cm) and a layer of cellophane or similar material, and fix it with non-irritating adhesive tape and bandage. The skin on the other side serves as a control. Adopt a closed test with an application time of 4 hours. The other side serves as a blank control. Apply continuously for 7 days. Observe the skin reaction of the applied part 24 hours, 48 hours, and 72 hours after the end of the application. According to Table 1 in Part 4 of the "Technical Specifications for Cosmetics Safety" (2015 Edition), conduct skin reaction scoring, and comprehensively evaluate based on the average value of the scores of the test animals. According to the highest average score at each observation time point of 24 hours, 48 hours, and 72 hours, determine the skin irritation intensity according to Table 2 in Part 4 to evaluate the irritation of the test sample to the skin. The test results are shown in Table 1.

[0060] Table 1. Skin irritation test The test results show that the nicotinamide anti-inflammatory emulsions prepared in Examples 1-5 of the present invention do not have skin irritation and will not cause irritation to the skin when directly applied to the skin surface, while the nicotinamide anti-inflammatory emulsions prepared in Comparative Examples 1-9 have slight irritation.

[0061] Test Example 2: pH-responsive sustained-release performance Take 2 portions of 0.2 parts by weight of the nicotinamide anti-inflammatory emulsions prepared in Examples 1- and Comparative Examples 1-5 and disperse them in 100 parts by weight of PBS buffer solution with pH 3.5 and pH 7.4 respectively. Conduct a sustained-release test by oscillating at a speed of 100 r / min in an environment of 37 °C. Sample at different time points and replenish fresh PBS buffer solution at the same temperature. Centrifuge the sample at 1000 r / min for 5 minutes, take the supernatant, and use an ultraviolet spectrophotometer to detect the content of nicotinamide in the supernatant. The test results are shown in Table 2 and Table 3.

[0062] Table 2. Cumulative release rate of nicotinamide at pH 3.5 (%) Table 3. Cumulative release rate of nicotinamide at pH 7.4 (%) It can be seen from the experimental results in Table 2 and Table 3 that the nicotinamide anti-inflammatory emulsions prepared in Examples 1-5 of the present invention have good pH-responsive sustained-release performance. The release effect of nicotinamide in an environment with a pH of 7.4 is poor, and it is difficult to achieve the anti-inflammatory effect. In an environment with a pH of 3.5, nicotinamide can be slowly released, enabling nicotinamide to exert its anti-inflammatory effect while avoiding excessive irritation to the skin caused by rapid release of nicotinamide; while for the nicotinamide anti-inflammatory emulsions prepared in Comparative Examples 1-5, the rapid release of nicotinamide in an environment with a pH of 3.5 will cause irritation to the skin.

[0063] Test Example 3: Soothing and anti-inflammatory function test An in vitro reconstructed epidermis model (Episkin TM ) was used to culture and test the expression of skin inflammatory factors (IL-6, TNF-α). In the model group, sodium dodecyl sulfate was added and exposed for 15 min, and then phosphate buffer solution was added and exposed for 30 min, followed by incubation for 48 h; in the blank group, an equal amount of phosphate buffer solution was added to replace sodium dodecyl sulfate in the model group. In the experimental group, 0.5% salicylic acid was thinly applied for 2-3 min and then replaced with an equal amount of nicotinamide anti-inflammatory emulsion for the phosphate buffer solution in the model group. In the control group, an equal amount of nicotinamide anti-inflammatory emulsion was directly used to replace the phosphate buffer solution in the model group. Among them, the experimental group was the nicotinamide anti-inflammatory emulsions prepared in Examples 1-5 and Comparative Examples 1-10, and the control group was the nicotinamide anti-inflammatory emulsion prepared in Example 5. The experimental results are shown in Table 4.

[0064] Table 4. Soothing and anti-inflammatory function test It can be found from the experimental results in Table 4 that compared with the nicotinamide anti-inflammatory emulsions prepared in Comparative Examples 1-9, the nicotinamide anti-inflammatory emulsions prepared in Examples 1-5 of the present invention have good soothing and anti-inflammatory effects, indicating that there is a certain synergistic anti-inflammatory effect among the nicotinamide sustained-release microspheres, plant extraction essence, cranberry seed oil, eucalyptus essential oil and rutin in the present invention; in addition, the anti-inflammatory effect of the control group is poor, indicating that the nicotinamide anti-inflammatory emulsion prepared in the examples of the present invention has a specific application scenario. When the skin is in an inflammatory state, the pH value increases. After restoring its normal pH with salicylic acid, and then using the nicotinamide anti-inflammatory emulsion prepared in the present invention, a better anti-inflammatory effect can be obtained.

[0065] The above-described embodiments have detailed the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements fall within the scope of the present invention claimed.

Claims

1. A method for preparing a nicotinamide anti-inflammatory emulsion, characterized in that: The preparation method comprises the following steps: Cranberry seed oil, eucalyptus essential oil, rutin, plant extract essence, cetearyl alcohol and Span-80 are dispersed in shea butter and stirred to obtain a first mixture, niacinamide sustained-release microspheres are dispersed in deionized water and stirred to obtain a second mixture, and the first mixture and the second mixture are subjected to homogenization reaction to obtain a niacinamide anti-inflammatory emulsion.

2. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 1, characterized in that: The preparation method of the nicotinamide sustained-release microspheres comprises the following steps: β-cyclodextrin, sodium periodate and ethylene glycol are reacted by stirring to obtain modified β-cyclodextrin, salicylic acid, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and ethylenediamine are reacted by stirring to obtain aminated salicylic acid, nicotinamide and cinnamoyl chloride are reacted by stirring to obtain modified nicotinamide, modified nicotinamide and modified β-cyclodextrin are reacted by stirring to obtain a nicotinamide complex, and the aminated salicylic acid and nicotinamide complex are reacted by stirring to obtain nicotinamide sustained-release microspheres.

3. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 1, characterized in that: The preparation of the plant extract essence comprises the following steps: The broccoli is chopped to obtain broccoli crumbs, ascorbic acid and calcium chloride are dispersed in a citric acid-phosphate buffer to obtain an activation solution, the broccoli crumbs are dispersed in the activation solution and sequentially subjected to stirring reaction, ultrasonic extraction and suction filtration to obtain a filtrate, and the filtrate is sequentially subjected to rotary evaporation, extraction, purification and drying to obtain the plant extract essence.

4. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 2, characterized in that: The weight ratio of the beta-cyclodextrin, sodium periodate and ethylene glycol is 1-1.5:0.45-0.55:0.5-1.

5. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 2, characterized in that: The weight ratio of nicotinamide to cinnamoyl chloride is 1-2:3-6.

6. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 2, characterized in that: The weight ratio of the aminosalicylic acid and niacinamide complex is 1.5-2:1.8-2.

2.

7. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 3, characterized in that: The size of the broccoli particles is 2-3 mm.

8. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 3, characterized in that: The weight ratio of ascorbic acid, calcium chloride and citric acid-phosphate buffer is 0.4-0.5:0.04-0.05:

200.

9. The method for preparing a nicotinamide anti-inflammatory emulsion according to claim 1, characterized in that: The weight ratio of the cranberry seed oil, eucalyptus essential oil, rutin, plant extract essence, cetearyl alcohol, Span-80 and shea butter is 0.3-0.5: 0.3-0.5: 0.3-0.5: 0.1-0.5: 1.5-2.5: 1.5-2.5: 8-16.

10. A nicotinamide anti-inflammatory emulsion prepared by the method for preparing a nicotinamide anti-inflammatory emulsion according to any one of claims 1 to 9.

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