Preparation method of borneol nicotinate and application thereof in efficacy skin care products
Patent Information
- Application Number
- CN202311627147.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-11-30
- Publication Date
- 2026-10-30
- Estimated Expiration
- 2043-11-30
AI Technical Summary
[0006]对于酯化反应，传统的酸催化剂如浓硫酸、对甲苯磺酸、硝酸等，虽然具有原料易得、价格低廉、催化效率高等优点，但其强腐蚀性、副产物多、产生大量废水、催化剂不易回收等诸多缺点也不容忽视
[0033]1.本发明提供的合成烟酸龙脑酯(NB)的方法，能够高效且绿色地制备烟酸龙脑酯(NB)，不使用有机溶剂，不产生废气、废水；且所用离子液体1-丙基磺酸-3-甲基咪唑硫酸氢盐[PrSO3HMIm][HSO4]能够回收重复使用，重复使用的催化效率依旧优良。
Smart Images
Figure CN117603136B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of natural resource modification and utilization technology, and specifically relates to a nicotinic acid borneol ester (NB), its preparation method, and its application in functional skin care products. Background Technology
[0002] By using whitening and spot-removing products to reduce or eliminate pigmentation, one can achieve the goal of skin whitening. In recent years, with the increasing demand for skin whitening products, the development of whitening and spot-removing cosmetics has attracted great attention from many cosmetic companies both domestically and internationally. These cosmetics are constantly being innovated and have become an important category of skincare products.
[0003] Pigmentation is formed in melanosomes within the basal layer of the epidermis. Tyrosine is first hydroxylated by tyrosinase to form dopa, which is then oxidized by tyrosinase to form dopaquinone. Subsequently, dopaquinone undergoes a series of reactions, primarily through natural oxidation, to ultimately generate melanin. Tyrosinase is a key enzyme in melanin biosynthesis; inhibiting tyrosinase activity can effectively suppress melanin production. Although many depigmenting ingredients have been developed, such as kojic acid, salicylic acid, niacinamide, arbutin, hydroquinone, corticosteroids, and retinoic acid, these ingredients suffer from high toxicity, low stability, poor skin permeability, and insufficient activity. Therefore, the demand for new, safer, and more effective depigmenting ingredients remains.
[0004] To develop new depigmenting ingredients, researchers are actively exploring compounds from various sources, such as natural products like chalcone, resveratrol, and coumarins, which exhibit inhibitory activity against mushroom tyrosinase. Niacinamide, derived from nicotinic acid, shows broad application prospects in organisms, potentially for skin whitening, brightening, and blemish removal. Currently, nicotinamide is widely used in whitening products from major brands. However, nicotinamide suffers from poor transdermal absorption, resulting in low bioavailability. Therefore, current research primarily focuses on derivatives such as ethyl nicotinate, benzyl nicotinate, and hexyl nicotinate, aiming to improve bioavailability while maintaining its activity.
[0005] Dextrorotatory borneol, also known as natural camphor, is a bicyclic monoterpene alcohol that can be extracted and crystallized from the resins or essential oils of plants in the Dipterocarpaceae family. Dextrorotatory borneol enhances the diffusion of hydrophilic substrates into cells by binding to specific cell membrane transport proteins, temporarily inactivating them, and forming transient micropores in the cell membrane phospholipid bilayer, promoting the intracellular penetration of hydrophilic drugs. By combining borneol and nicotinic acid through esterification, the shortcomings of nicotinic acid can be overcome, enhancing the whitening effect and providing a new raw material for the whitening cosmetics industry.
[0006] For esterification reactions, traditional acid catalysts such as concentrated sulfuric acid, p-toluenesulfonic acid, and nitric acid, while possessing advantages such as readily available raw materials, low cost, and high catalytic efficiency, also have significant drawbacks, including strong corrosivity, numerous byproducts, large amounts of wastewater generation, and difficulty in catalyst recovery. Ionic liquids, as a rapidly developing "green solvent," are widely used in organic synthesis, serving as catalysts, organic solvents, and extractants. Ionic liquids have demonstrated unique roles in hydrogenation, esterification, Friedel-Crafts reactions, Heck reactions, Diels-Alder reactions, asymmetric catalysis, and separation and purification. Summary of the Invention
[0007] The primary objective of this invention is to overcome the shortcomings and deficiencies of the prior art and provide a green preparation method for nicotinic acid bornyl ester (NB).
[0008] Another object of the present invention is to provide the use of the above-mentioned nicotinic acid borneol ester (NB) in medicaments for the treatment and prevention of skin pigmentation diseases.
[0009] Another object of the present invention is to provide the application of the above-mentioned nicotinic acid bornyl ester (NB) in functional skin care products.
[0010] The objective of this invention is achieved through the following technical solution: a nicotinic acid borneol ester (NB), the structural formula of which is shown below:
[0011]
[0012] The preparation method of the above-mentioned nicotinic acid borneol ester (NB) includes the following steps: adding nicotinic acid and borneol into a flask containing 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4], refluxing under stirring, and then performing post-treatment to obtain nicotinic acid borneol ester (NB); more preferably, the method includes the following steps:
[0013] (1) Nicotinic acid, dextrorotatory borneol and 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] were added to a three-necked round-bottom flask equipped with a reflux condenser and a thermometer. The reaction was carried out under stirring and the reaction progress was monitored by TLC. The reaction was completed and the mixture became biphase.
[0014] (2) After the reaction is complete, the two phases are separated to obtain a mixture of crude product and ionic liquid. Unreacted raw materials and residual products in the ionic liquid phase are extracted with dichloromethane. The separated ionic liquid is then dehydrated under vacuum at 80°C and recycled.
[0015] (3) Dissolve the crude product in an appropriate amount of dichloromethane and separate and purify it by column chromatography to obtain a pale yellow oily liquid, which is nicotinic acid bornyl ester (NB).
[0016] The nicotinic acid and borneol mentioned in step (1) are preferably mixed in a molar ratio of 1:1 to 1.5; more preferably 1:1 to 1.2.
[0017] The amount of 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] mentioned in step (1) is preferably 5-10 mL per 1g of reactant.
[0018] The reflux temperature mentioned in step (1) is preferably 80-100℃, more preferably 95℃.
[0019] The stirring speed in step (1) is preferably 400-800 r / min.
[0020] The preferred reaction time condition in step (1) is 2 to 4 hours.
[0021] The extraction in step (2) is preferably performed using one of dichloromethane and tetrahydrofuran; more preferably, dichloromethane.
[0022] The preferred number of extractions in step (2) is 3.
[0023] The preferred packing material used for column chromatography in step (3) is silica gel with a mesh size of 100 to 400; more preferably, silica gel with a mesh size of 300 to 400.
[0024] The eluent used in the column chromatography method described in step (3) is preferably a solution obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 100:10.
[0025] The column chromatography method described in step (3) preferably includes the following steps: loading the sample, eluting impurities with a solution of petroleum ether and ethyl acetate in a volume ratio of 100:1, and eluting with a gradient of a solution of petroleum ether and ethyl acetate in a volume ratio of 100:10 to obtain a pale yellow liquid, which is nicotinic acid bornyl ester (NB).
[0026] The concentration gradient solution of petroleum ether and ethyl acetate in a volume ratio of 100:10 refers to a solution obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 100:5 to 10.
[0027] The present invention also provides the application of the above-mentioned nicotinic acid borneol ester (NB) or nicotinic acid borneol ester (NB) prepared by the above preparation method in whitening products.
[0028] This invention further protects a skin-whitening and freckle-removing cosmetic containing the above-mentioned skin-whitening and freckle-removing compound or nicotinic acid borneol ester (NB) obtained by the above preparation method.
[0029] Furthermore, the content of nicotinic acid bornyl ester (NB) in the cosmetic is 0.5-3% by mass, preferably 1-3%; more preferably 1%. This preference is based on fully utilizing the synergistic effect of nicotinic acid bornyl ester (NB) with other active ingredients in the cosmetic to achieve the inhibition of tyrosinase and melanin synthesis, thereby achieving the best whitening and spot-removing effects.
[0030] Furthermore, the cosmetic is any one of serum, lotion, cream, gel, or mask, preferably a serum.
[0031] As a further improvement of the present invention, the present invention also provides an essence prepared from the following raw materials in weight percentage: 60-70% deionized water, 0.1-0.3% allantoin, 0.1-0.3% disodium EDTA, 0.05-0.1% anhydrous sodium sulfite, 6% glyceryl polyether-263, 4-8% glycerol, 0.5-1% Aristoflex AVC, 2-4% Plantasens Natural Emulsifier HP30, 1-1.5% vitamin E, 4-6% cetearyl alcohol, 2-4% squalane, 2-4% cyclodimethylsiloxane, 0.5-1% titanium dioxide, 2-4% 1,2-pentanediol, 1-2% borneol nicotinic acid (NB), 4-6% butylene glycol, and 0.5-1% p-hydroxyacetophenone.
[0032] The present invention has the following advantages and effects compared with the prior art:
[0033] 1. The method for synthesizing nicotinic acid bornyl ester (NB) provided by the present invention can efficiently and greenly prepare nicotinic acid bornyl ester (NB), without using organic solvents and without generating waste gas or wastewater; and the ionic liquid 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] used can be recycled and reused, and the catalytic efficiency remains excellent after reuse.
[0034] 2. The nicotinic acid borneol ester (NB) provided by this invention has a stable structure and significantly inhibits melanin synthesis and tyrosinase activity. It can be added to whitening products such as cosmetics as a drug for treating and preventing hyperpigmentation diseases, and has broad application potential.
[0035] 3. The nicotinic acid borneol ester (NB) of the present invention is non-irritating to the human body, safe, reliable and without toxic side effects when used in whitening products. Attached Figure Description
[0036] Figure 1 The reaction equation diagram for Example 1 of the present invention is shown below;
[0037] Figure 2 The hydrogen nuclear magnetic resonance spectrum of the product of Example 1 of this invention;
[0038] Figure 3 This is a high-resolution mass spectrum of the product of Example 1 of the present invention;
[0039] Figure 4 The results of experiments on the inhibition of tyrosinase activity by nicotinic acid bornyl ester (NB) are presented. Detailed Implementation
[0040] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto.
[0041] Example 1
[0042] This embodiment provides a method for preparing nicotinic acid bornyl ester (NB), such as... Figure 1 As shown, it includes the following steps:
[0043] (1) Add 1.23 g (10 mmol) nicotinic acid, 1.54 g (10 mmol) dextrorotatory borneol and 20 ml of 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] to a dry three-necked flask equipped with a magnetic stirrer in sequence. Heat to 95 °C and reflux for 4 h at 400-600 r / min. Monitor the reaction progress by TLC.
[0044] (2) After the reaction is complete, separate the two phases to obtain the crude product phase and the ionic liquid phase respectively. Use 30 mL of dichloromethane to extract the unreacted raw materials and residual products in the ionic liquid phase. After extraction 3 times, dehydrate the ionic liquid under vacuum at 80 °C for 1 h and recycle it.
[0045] (3) The analysis was performed using a silica gel column with an average particle size of 37 μm. After loading the sample, it was first washed with 100 mL of a slightly smaller eluent (petroleum ether: ethyl acetate = 100:1 by volume) to remove impurities with low polarity. Then, it was eluted with a gradient solution of petroleum ether and ethyl acetate at a volume ratio of 100:10. After rotary evaporation, 2.4683 g of pale yellow liquid nicotinic acid bornyl ester (NB) was obtained, with a yield of 89%.
[0046] (A) Nuclear magnetic resonance image as shown Figure 2As shown: 0.92 (3H,s,CH3), 0.94 (3H,s,CH3), 0.97 (3H,s,CH3), 1.12-1.16 (1H,m,CH), 1.28-1.46 (2H,m,CH2), 1.75-1.85 (2H,m,CH2), 2.12-2.14 (1H,m,CH2), 2.45-2.52 (1H,m,CH2), 5.14-5.18 (1H,m,CH), 7.38-7.42 (1H,m,pyridine ring), 8.31-8.32 (1H,m,pyridine ring), 8.75-8.79 (1H,m,pyridine ring), 9.25-9.26 (1H,m,pyridine ring).
[0047] (B) High-resolution mass spectrum as shown Figure 3 As shown: ESI-HRMS[M+H] + , m / z: 260.1654.
[0048] (B) Figure 2 and Figure 3 The successful synthesis of nicotinic acid borneol ester (NB) was also demonstrated, and its structural formula is as follows:
[0049]
[0050] Example 2
[0051] Based on Example 1 above, this example further provides a method for preparing nicotinic acid bornyl ester (NB), including the following steps:
[0052] (1) Add 1.23 g (10 mmol) nicotinic acid, 1.54 g (10 mmol) dextrorotatory borneol and 20 ml of 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] recovered in Example 1 to a dry three-necked flask with a magnetic stirrer in sequence. Heat to 95 °C at 400-600 r / min and reflux for 4 h. The reaction progress is monitored by TLC.
[0053] (2) After the reaction is complete, separate the two phases to obtain the crude product phase and the ionic liquid phase respectively. Use 30 mL of dichloromethane to extract the unreacted raw materials and residual products in the ionic liquid phase. After extraction 3 times, dehydrate the ionic liquid under vacuum at 80 °C for 1 h and recycle it.
[0054] (3) The analysis was performed using a silica gel column with an average particle size of 37 μm. After loading the sample, it was first washed with 100 mL of a slightly smaller eluent (petroleum ether: ethyl acetate = 100:1 by volume) to remove impurities with low polarity. Then, it was eluted with a gradient solution of petroleum ether and ethyl acetate at a volume ratio of 100:10. After rotary evaporation, 2.3908 g of pale yellow liquid nicotinic acid bornyl ester (NB) was obtained, with a yield of 86%.
[0055] In this embodiment, the ionic liquid 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] used was the 1-propylsulfonic acid-3-methylimidazolium hydrogen sulfate [PrSO3HMIm][HSO4] recovered in Example 1, yielding 2.3908 g of pale yellow liquid nicotinic acid bornyl ester (NB), with a yield of 86%. Compared with the results in Example 1, the catalytic efficiency remains excellent even after repeated use.
[0056] Example 3
[0057] This embodiment further provides the application of nicotinic acid borneol ester (NB) in the inhibition of tyrosinase.
[0058] Cells were seeded in RPMI 1640 medium containing 10% newborn calf serum (containing 100 μg / mL penicillin and 100 μg / mL streptomycin) and cultured at 37°C, 5% CO2 and saturated humidity. The cells adhered to the culture medium and were passaged using trypsin solution. Cells in the logarithmic growth phase were used for experiments.
[0059] Add 3×10 to the 6-well culture plate 4 Two mL of mouse melanoma B16 cells at a density of cells / mL were cultured in a CO2 incubator for 24 h. A gradient of nicotinic acid-borneol ester (NB) concentrations from 50 to 500 μg / mL was used, with a positive control group containing kojic acid (500 μg / mL) and a blank control group containing 0.1% DMSO. After 24 h of culture, the supernatant was aspirated, and the cells were digested with trypsin for 30 s, centrifuged at 1100 rpm for 5 min, the supernatant was discarded, and the cells were cleaned twice with PBS. 1% Triton X-100 was added to each well, and the cells were then frozen at -80℃ for 30 min. Cells were lysed at room temperature until complete lysis, then heated in a 37℃ water bath for 5 min and mixed with 200 μL of 0.1% levodopa solution. The mixture was incubated at 37℃ for 2 h, and the absorbance was measured at 490 nm using a microplate reader. Tyrosinase activity was calculated.
[0060] Tyrosinase activity = (Drug group / Control group) × 100%
[0061] Test results as follows Figure 4As shown, the experimental results demonstrate that the synthesized nicotinic acid bornyl ester (NB) can inhibit tyrosinase activity in a concentration-dependent manner. At a dosage concentration of 400 μg / mL, the tyrosinase inhibitory ability of nicotinic acid bornyl ester (NB) is higher than that of the positive control kojic acid.
[0062] Example 4
[0063] This embodiment further provides an experiment on the inhibition of melanin synthesis in zebrafish by nicotinic borneol ester (NB).
[0064] Wild-type AB zebrafish were used in the experiment. The zebrafish were reared according to DB32 / T 3979-2021 "Technical Conditions for the Rearing of Experimental Zebrafish". The night before the experiment, sexually mature zebrafish older than 4 months were selected and placed in spawning boxes with baffles at a female-to-male ratio of 1:2, kept in the dark. The next morning, the light source was turned on, and the baffles of the spawning boxes were removed to allow mating and spawning. One hour after mating, the spawning of adult fish in each tank was checked. Embryos produced by the mating were collected into 100mm culture dishes. After removing foreign objects from the culture dishes, they were placed in a constant temperature incubator for incubation.
[0065] Under a stereomicroscope, embryos with normal development (6-8 hpf) were randomly selected using a plastic dropper for the experiment. Twenty embryos were added to each well of a 6-well cell culture plate. After removing the culture water with a plastic pipette, 5.0 ml of prepared nicotinic acid bornyl ester (NB) dilution (100-1000 μg / mL) was added to each well of the 6-well cell culture plate, with three parallel groups. The plates were then covered and incubated at 28±0.5℃. A solution control group and a positive control group (arbutin (1000 μg / mL)) were also set up.
[0066] Images were taken at 72 hpf. For each experiment, at least three zebrafish embryos were used for photography. During photography, the embryos were held upright, and the image was taken from a top-down view focusing on the head. The distribution area and number of melanin granules on the zebrafish body surface were observed. The images were analyzed using image analysis software (such as ImageJ). The optical density (OD) value was used to represent the melanin signal intensity in the zebrafish head, and the relative melanin content was calculated.
[0067] Relative zebrafish melanin content (%) = S1 / S0 × 100%
[0068] In the formula:
[0069] S0—The average melanin content in the solution control group;
[0070] S1—The average melanin content of the sample group;
[0071] The specific results are shown in Table 1. As can be seen from the table, nicotinic acid bornyl ester (NB) has a strong inhibitory effect on melanin synthesis in a concentration-dependent manner. At an application concentration of 1000 μg / mL, melanin in zebrafish embryos was significantly reduced, and this effect was superior to that of the positive control arbutin, indicating that nicotinic acid bornyl ester (NB) has great potential.
[0072] Table 1. Effects of nicotinic acid borneol ester (NB) on melanin synthesis
[0073]
[0074] Example 5
[0075] The synthesized nicotinic acid borneol ester (NB) was prepared into a whitening and spot-removing essence. The formula of the whitening and spot-removing essence containing nicotinic acid borneol ester (NB) is shown in Table 2.
[0076] Table 2. Whitening and Spot-Removing Essence Formula
[0077]
[0078] The preparation method of the whitening and spot-removing essence containing nicotinic acid bornyl ester (NB) is as follows:
[0079] (1) Weigh allantoin, disodium EDTA, anhydrous sodium sulfite, glycerol polyether-26, glycerol, and Aristoflex AVC from phase A raw material, mix and heat to 80°C, soak and swell, and record as phase A.
[0080] (2) Mix Plantasens Natural Emulsifier HP30, Vitamin E, Cetearyl Alcohol, Squalane, Cyclodimethylsiloxane, Titanium Dioxide, 1,2-Pentanediol, etc. in Phase B raw materials and heat to 80°C. The solids are completely dissolved and homogenized for 2-3 minutes, and the powder is evenly dispersed.
[0081] (3) Quickly add phase B to phase A to obtain a mixture, and emulsify and homogenize for 3-4 minutes at a speed of 8000 r / min; after homogenization, stir for 15 minutes.
[0082] (4) Dissolve the nicotinic acid borneol ester (NB), butanediol and 1,2-pentanediol in the C phase raw material, heat to 60°C, and then quickly add to the mixture obtained in step (3). Homogenize for 2-3 minutes at a speed of 8000 r / min.
[0083] (5) Cool down to 30°C, add phase D to the mixture obtained in step (4), and stir evenly to obtain the whitening and spot-removing essence containing nicotinic acid borneol ester (NB).
[0084] Comparative Example 1
[0085] Compared with Example 5, the whitening and spot-removing compounds prepared in Examples 1 and 2 were not added, and all other conditions remained unchanged.
[0086] Test case
[0087] Human efficacy trials
[0088] I. Human Skin Patch Test
[0089] Experimental Methods: Thirty volunteers aged 22-45 years who met the experimental requirements were selected as subjects, with an equal number of men and women. A patch test was performed on the inner forearm of the volunteers. The test product was the product obtained in Example 5. The test duration was 24 hours. After 24 hours, the patch device was removed. Any remaining sample could be gently wiped clean with a damp tissue. Skin reactions were observed at 0.5, 24, and 48 hours after removal. The grading criteria for skin reactions in the occlusive patch test are shown in Table 3.
[0090] Table 3. Grading Criteria for Adverse Skin Reactions
[0091]
[0092]
[0093] The results of the human skin patch test are shown in Table 4.
[0094] Table 4. Results of human skin patch test
[0095]
[0096] Human skin patch test results showed that 0 out of 30 people experienced adverse skin reactions, indicating that the whitening and freckle-removing cosmetic of the present invention is safe to use.
[0097] II. Human Efficacy Trials
[0098] Experimental Methods: Forty healthy volunteers aged 20-45 years (half male and half female) were recruited and randomly divided into two groups of 20 each. The test site was the inner side of the left and right forearms, 5cm from the base of the palm, covering an area of 3×3cm. Before the experiment, the pigment content and skin color of the test site were measured using a Mexameter MX 18 skin melanin and hemoglobin analyzer, repeated three times, and the average value was taken. After the experiment began, the experimental group used the cosmetic sample of Example 5 of this invention for four consecutive weeks, while the control group used the cosmetic sample of Comparative Example 1. The samples were used twice daily, morning and evening, and the melanin value of the test site was measured every seven days. Before the test, the participants were required to sit quietly for 30 minutes in an environment with an indoor temperature of 21±1℃ and a relative humidity of 50±10%. Three parallel data points were measured each time, and the average value was taken. The results are shown in Table 5.
[0099] Table 5. Whitening and spot-removing essence containing nicotinic acid borneol ester (NB) component: melanin-inhibiting effect
[0100]
[0101] As shown in Table 5, compared with before use, after using the whitening liquid crystal emulsion sample containing nicotinic acid borneol ester (NB) component, with the increase of test time, the melanin content measured in the whitening and spot-removing essence group with added nicotinic acid borneol ester (NB) component gradually and significantly decreased, while the melanin content in the control group without added nicotinic acid borneol ester (NB) component did not show significant changes. This further illustrates that nicotinic acid borneol ester (NB) component can reduce the formation of melanin, thereby exerting a whitening effect.
[0102] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and are included in the present invention.
Claims
1. A whitening and freckle-removing essence, characterized in that, The freckle-removing essence is prepared according to the following weight percentages: allantoin 0.1-0.3%, EDTA-disodium 0.1-0.3%, anhydrous sodium sulfite 0.05-0.1%, glyceryl polyether-26 3-6%, glycerin 4-8%, Aristoflex AVC 0.5-1%, Plantasens Natural Emulsifier HP30 2-4%, vitamin E 1-1.5%, cetearyl alcohol 4-6%, squalane 2-4%, cyclodimethylsiloxane 2-4%, titanium dioxide 0.5-1%, 1,2-pentanediol 2-4%, nicotinic borneol ester 1-2%, butylene glycol 4-6%, p-hydroxyacetophenone 0.5-1%, with the balance being deionized water.
2. A method for preparing the whitening and freckle-removing essence as described in claim 1, characterized in that, Includes the following steps: (1) Weigh allantoin, disodium EDTA, anhydrous sodium sulfite, glycerol polyether-26, glycerol, and Aristoflex AVC, mix and heat to 80°C, soak and swell, and record as phase A; (2) Mix Plantasens Natural Emulsifier HP30, Vitamin E, Cetearyl Alcohol, Squalane, Cyclodimethylsiloxane, Titanium Dioxide and 1,2-Pentanediol in the raw materials and heat to 80°C. The solids are completely dissolved and homogenized for 2-3 minutes. The powder is evenly dispersed and recorded as phase B. (3) Quickly add phase B to phase A to obtain a mixture, and emulsify and homogenize for 3-4 minutes at a speed of 8000 r / min; after homogenization, stir for 15 minutes. (4) Mix and dissolve nicotinic acid borneol, butanediol and 1,2-pentanediol, heat to 60°C, and then quickly add to the mixture obtained in step (3). Homogenize for 2-3 minutes at a speed of 8000 r / min. (5) Cool down to 30°C, add p-hydroxyacetophenone and butylene glycol to the mixture obtained in step (4), stir evenly to obtain the whitening and spot-removing essence containing nicotinic acid borneol ester (NB).