A whitening and freckle-removing nano-emulsion cream and a supergravity technology preparation method thereof

Abstract

This invention discloses a whitening and freckle-removing nano-cream and its preparation method using supergravity technology. The whitening and freckle-removing nano-cream comprises the following raw materials in parts by weight: 2-5 parts of water-in-oil emulsifier, 2-5 parts of oil-in-water emulsifier, 3-5 parts of liquid oil, 1-3 parts of solid oil, 1-3 parts of tocopheryl acetate, 0.5-2 parts of laurocapram, 0.1-0.25 parts of propylparaben, 10-30 parts of glycerin, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium lauryl sulfate, 0.5-1 parts of antioxidant, 1.8-4 parts of whitening and freckle-removing active ingredients, and deionized water added to a total of 100 parts. The present invention also discloses a method for preparing the whitening and freckle-removing nano-cream. The whitening and freckle-removing nano-cream of the present invention has a particle size between 70-130nm. Under the conditions of storage at room temperature, 40℃ and 4℃ for ≥90 days, the appearance, particle size and content of whitening and freckle-removing active ingredients do not change significantly.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology, and in particular relates to a whitening and freckle-removing nano-cream and its preparation method using supergravity technology. Background Technology

[0002] The formation of age spots is due to the melanocytes in the basal layer of the skin. When these cells are affected by internal and external factors, they release tyrosinase, which, through a series of catalytic actions, forms melanin granules. When melanin continuously aggregates in the epidermis, age spots are formed. The basal layer of the skin is located at the bottom layer of the epidermis, making it difficult for drugs to penetrate the stratum corneum and reach it, thus hindering their effectiveness. Applying nano-transdermal drug delivery technology to the treatment of age spots can significantly improve treatment efficacy, reduce irritation, and enhance the stability of active ingredients.

[0003] A novel multi-component drug delivery system, nanoemulsion, can simultaneously load both lipid-soluble and water-soluble drugs, and can also increase the solubility of poorly soluble drugs, exhibiting sustained-release and targeted effects. Furthermore, nanoemulsions outperform liposomes in terms of scale-up and stability, are easier to industrialize, and have lower toxicity. Compared to conventional emulsions, micelles, or suspensions, they possess higher thermodynamic stability, thus extending shelf life. However, nanoemulsions are limited by their low viscosity, resulting in shorter residence time and spreadability. Cream systems, on the other hand, have higher viscosity than emulsions, leading to longer skin residence time and spreadability; therefore, nano-sized creams offer significant advantages in skincare and the treatment of skin diseases.

[0004] Tsujimoto H et al. found in skin permeability experiments that only particles with a diameter ≤200nm can penetrate skin pores and the stratum corneum to reach the basal layer of the skin (Tsujimoto H, Hara K. Development of functional skin carecosmetics using biodegradable PLGA nanospheres[M] / / Nanoparticle Technology Handbook.Elsevier,2018:445-450.).

[0005] Chinese patent application CN106389168A discloses a positively charged water-in-oil nano-cream with whitening and freckle-removing effects, with a particle size of about 120-280nm. However, it requires heating the water and oil phases separately, homogenizing in two steps, filtering with a membrane filter, and subsequent stirring. The process is relatively complex, time-consuming, and not easy to industrialize.

[0006] Chinese patent application CN 104382801A discloses a nanoemulsion and gel for whitening and removing freckles. The liquid nanoemulsion has a particle size between 70-100 nm, and is then made into a gel to improve its skin adhesion and retention time. However, the final gel particle size is not reported. Therefore, the invention of a whitening and freckle-removing cream with small particle size and high skin adhesion is very necessary.

[0007] Combining ingredients with similar effects can have a synergistic effect and can also reduce the amount of related ingredients added. For example, hydroquinone, as a skin depigmenting agent, has a certain degree of irritation. National regulations govern drugs containing hydroquinone; the maximum content of hydroquinone in over-the-counter drugs is 2%, and in prescription drugs, it is 4%. Combination therapy can be used to reduce the dosage of hydroquinone while improving treatment efficacy. Vitamin E is a fat-soluble vitamin with antioxidant, moisturizing, and antipruritic effects, and can be used as an adjunct treatment for melasma, freckles, and other conditions. Some doctors recommend using hydroquinone cream and vitamin E cream to treat pigmentation. Hydroquinone cream can effectively reduce the number and size of subcutaneous pigment cells, thus achieving a whitening effect. Vitamin E cream is a strong antioxidant that can combat free radicals, achieving skin whitening and pigmentation removal. Therefore, combining vitamin E and hydroquinone to create a whitening and pigmentation-removing nano-cream can synergistically remove pigmentation and improve treatment efficacy.

[0008] Therefore, it is essential to develop a whitening and freckle-removing nano-cream with small particle size, good transdermal effect, good stability, and low irritation. The use of supergravity technology makes it possible to commercialize this whitening and freckle-removing nano-cream. Summary of the Invention

[0009] The first technical problem this invention aims to solve is to provide a whitening and freckle-removing nano-cream. This nano-cream has small particle size, good transdermal effect, high stability, and low irritation. The whitening and freckle-removing nano-cream of this invention has a particle size between 70-130 nm. After storage at room temperature, 40℃, and 4℃ for ≥90 days, its appearance, particle size, and content of whitening and freckle-removing active ingredients show no significant changes. Hypergravity technology makes the nano-sizing of hydroquinone cream possible. Hypergravity technology enhances the multiphase flow transfer and reaction process. In this process, the liquid is dispersed and broken by the filler under strong centrifugal force, continuously renewing the surface area to achieve high dispersion, high turbulence, and strong mixing. The advantages of this technology are as follows: small product particle size, small equipment size, low energy consumption, simple operation, low cost, safety, flexibility, and easy scale-up, making it suitable for industrial production.

[0010] The second technical problem this invention aims to solve is to provide a method for preparing a whitening and freckle-removing nano-cream using supergravity technology. This preparation method is simple, low-cost, easily scaled up, and suitable for industrial production.

[0011] To solve the first technical problem mentioned above, the present invention adopts the following technical solution:

[0012] A whitening and freckle-removing nano-cream, comprising the following ingredients in parts by weight:

[0013]

[0014]

[0015] Preferably, the oil-in-water emulsifier is selected from one or more of Tween 80, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene-21 stearyl ether, and polyglycerol-10 laurate.

[0016] Preferably, the water-in-oil emulsifier is selected from one or more of the following: triglyceride monostearate, Span 6, polyoxyethylene-2 ​​stearyl alcohol ether, and stearic acid.

[0017] Preferably, the ratio of the water-in-oil emulsifier to the oil-in-water emulsifier is 1:3 to 3:1.

[0018] Preferably, the liquid oil is one or more of polydimethylsiloxane, glyceryl caprylate, myristate, and palm oil.

[0019] Preferably, the solid grease is one or more of hexadecane, octadecane, and paraffin.

[0020] Preferably, the antioxidant is one or more of sodium metabisulfite and anhydrous sodium sulfite.

[0021] Preferably, the whitening and freckle-removing active ingredient is one or more of glycyrrhizin, hydroquinone, α-arbutin, nicotinamide, ascorbate glucoside, and tranexamic acid.

[0022] To solve the second technical problem mentioned above, the present invention adopts the following technical solution:

[0023] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0024] 1) Weigh 2-5 parts of oil-in-water emulsifier, 2-5 parts of water-in-oil emulsifier, 3-5 parts of liquid oil, 1-3 parts of solid oil, 1-3 parts of tocopheryl acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath while stirring until homogeneous to obtain the oil phase;

[0025] 2) Weigh out 10-30 parts of glycerin, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium dodecyl sulfate, and an appropriate amount of deionized water, and heat and stir evenly in a water bath to obtain an aqueous phase;

[0026] 3) Add the oil phase and water phase to the jacketed flask, connect the flask to the centrifugal rotating packed bed and a circulating water bath, and maintain the temperature at the same temperature as in steps 1) and 2); start the centrifugal rotating packed bed, and the oil and water phases circulate and emulsify between the centrifugal rotating packed bed and the jacketed reactor. The droplets collide violently in the centrifugal environment and are repeatedly mixed and sheared to obtain VE nanoemulsion.

[0027] 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool it to a certain temperature, then add 1.8-4 parts of finely ground whitening and spot-removing active ingredients and 0.5-1 parts of antioxidant, stir until cooled to room temperature, and you will get the whitening and spot-removing nanoemulsion cream.

[0028] Preferably, the water bath heating temperature in steps 1), 2), and 3) is 60-80℃.

[0029] Preferably, in step 3), the time for cyclic emulsification is 1-20 minutes.

[0030] Preferably, in step 3), the circulation flow rate of the circulating emulsification is 50-150 ml / min.

[0031] Preferably, in step 3), the rotational speed of the rotary filling bed is 1000-2500 rpm.

[0032] Preferably, in step 4), the specific temperature is 30-45℃.

[0033] Preferably, in step 4), the stirring speed is 300-500 rpm.

[0034] Any range described in this invention includes the endpoint, any value between the endpoints, and any subrange consisting of the endpoint or any value between the endpoints.

[0035] Unless otherwise specified, all raw materials used in this invention can be obtained commercially, and the equipment used in this invention can be conventional equipment in the relevant field or refer to existing technology in the relevant field.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] 1. The whitening and freckle-removing nano-cream prepared by the method of the present invention has a particle size range of 70-130nm, which is smaller than that of traditional creams. It shows no significant changes in appearance, particle size, or content of whitening and freckle-removing active ingredients after being stored at room temperature, 40℃, and 4℃ for ≥90 days, and has good stability.

[0038] 2. The preparation method of the present invention utilizes supergravity technology to enhance the process, which significantly shortens the emulsification time compared with the traditional emulsification method, thereby shortening the production cycle. It is highly efficient, low in cost, and very easy to scale up, achieving the invention goal of industrial production.

[0039] 3. Combining strong antioxidant vitamin E with skin-lightening or whitening ingredients can help combat free radicals, whiten the skin, and remove and improve pigmentation. It can also reduce the amount of irritating active substances added, reduce irritation, and improve treatment effectiveness. Attached Figure Description

[0040] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0041] Figure 1 Transmission electron microscopy image of the whitening and freckle-removing nano-cream prepared in Example 1 and its fitted normal distribution diagram;

[0042] Figure 2 Transmission electron microscopy image of the whitening and freckle-removing nano-cream prepared in Example 2 and its fitted normal distribution diagram;

[0043] Figure 3 This is a picture of the whitening and freckle-removing nano-cream prepared in Example 1;

[0044] Figure 4 The graph shows the changes in the content of whitening and freckle-removing active ingredients in the whitening and freckle-removing nano-cream prepared in Example 1 after standing at room temperature, 40°C, and 4°C for 90 days.

[0045] Figure 5 Transmission electron microscopy image of the whitening and freckle-removing nano-cream prepared in Comparative Example 1 and its fitted normal distribution diagram;

[0046] Figure 6 The image shows the actual product of the whitening and freckle-removing nano-cream prepared in Comparative Example 2.

[0047] Figure 7 Transmission electron microscopy image of the whitening and freckle-removing nano-cream prepared in Comparative Example 5;

[0048] Figure 8 Transmission electron microscopy image of the whitening and freckle-removing nano-cream prepared in Comparative Example 6; Detailed Implementation

[0049] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0050] As one aspect of the present invention, a whitening and freckle-removing nano-cream cream comprises the following raw materials in parts by weight:

[0051]

[0052] According to certain embodiments of the present invention, the oil-in-water emulsifier is selected from one or more of Tween 80, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene-21 stearyl ether, and polyglycerol-10 laurate.

[0053] According to certain embodiments of the present invention, the water-in-oil emulsifier is selected from one or more of glyceryl monostearate, Span 6, polyoxyethylene-2 ​​stearyl alcohol ether, and stearic acid.

[0054] According to certain embodiments of the present invention, the ratio of the water-in-oil emulsifier to the oil-in-water emulsifier is 1:3 to 3:1.

[0055] According to certain embodiments of the present invention, the liquid oil is one or more of polydimethylsiloxane, glyceryl caprylate, myristate, and palm oil.

[0056] According to certain embodiments of the present invention, the solid grease is one or more of hexadecane, octadecane, and paraffin.

[0057] According to certain embodiments of the present invention, the antioxidant is one or more of sodium metabisulfite and anhydrous sodium sulfite.

[0058] According to certain embodiments of the present invention, the whitening and freckle-removing active ingredients are one or more of glycyrrhizin, hydroquinone, α-arbutin, nicotinamide, ascorbyl glucoside, and tranexamic acid.

[0059] To solve the second technical problem mentioned above, the present invention adopts the following technical solution:

[0060] A method for preparing a whitening and freckle-removing nano-cream includes the following steps:

[0061] 1) Weigh 2-5 parts of oil-in-water emulsifier, 2-5 parts of water-in-oil emulsifier, 3-5 parts of liquid oil, 1-3 parts of solid oil, 1-3 parts of tocopheryl acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath while stirring until homogeneous to obtain the oil phase;

[0062] 2) Weigh out 10-30 parts of glycerin, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium dodecyl sulfate, and an appropriate amount of deionized water, and heat and stir evenly in a water bath to obtain an aqueous phase;

[0063] 3) Add the oil phase and water phase to the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at the same temperature as in steps 1) and 2); start the centrifugal rotating packed bed, and the oil and water phases circulate and emulsify between the centrifugal rotating packed bed and the jacketed reactor. The droplets collide violently in the centrifugal environment, and are repeatedly mixed and sheared to obtain VE nanoemulsion.

[0064] 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool it to a certain temperature, then add 1.8-4 parts of finely ground whitening and spot-removing active ingredients and 0.5-1 parts of antioxidant, stir until cooled to room temperature, and you will get the whitening and spot-removing nanoemulsion cream.

[0065] According to certain embodiments of the present invention, the water bath heating temperature in steps 1), 2), and 3) is 60-80°C.

[0066] According to some embodiments of the present invention, in step 3), the time for cyclic emulsification is 10-20 min.

[0067] According to certain embodiments of the present invention, in step 3), the circulation flow rate of the circulating emulsification is 50-150 ml / min.

[0068] According to some embodiments of the present invention, in step 3), the rotational speed of the rotary filling bed is 1000-2500 rpm.

[0069] According to some embodiments of the present invention, in step 4), the certain temperature is 30-45°C.

[0070] According to some embodiments of the present invention, in step 4), the stirring speed is 300-500 rpm.

[0071] Example 1

[0072] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0073] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 5.5 parts of polyoxyethylene 40 hydrogenated castor oil, and 2.5 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0074] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0075] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0076] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts of glycyrrhizin and 0.5 parts of sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and spot-removing nanoemulsion cream.

[0077] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 79.29 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0078] Example 2

[0079] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0080] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 4 parts of polyoxyethylene 40 hydrogenated castor oil, and 4 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0081] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0082] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0083] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts hydroquinone and 0.5 parts sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0084] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 76.48 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0085] Example 3

[0086] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0087] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 4 parts of Tween 80, and 4 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0088] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0089] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0090] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts hydroquinone and 0.5 parts sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0091] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 105.46 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0092] Example 4

[0093] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0094] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0095] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0096] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2500 rpm, and the circulation flow rate is 100 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0097] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts of α-arbutin and 0.5 parts of sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and spot-removing nanoemulsion cream.

[0098] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 103.18 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0099] Example 5

[0100] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0101] 1) Weigh 5 parts caprylic / capric triglyceride, 1 part hexadecane, 2 parts tocopheryl acetate, 1.5 parts laurocapramone, 0.1 part propylparaben, 4 parts polyoxyethylene 40 hydrogenated castor oil, and 4 parts triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 75°C until homogeneous, and use this mixture as the oil phase.

[0102] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 75°C until they are mixed evenly, and use this as the aqueous phase.

[0103] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 75℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 100 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0104] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 35°C, weigh out 2 parts hydroquinone and 0.5 parts sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0105] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 97.99 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or whitening and freckle-removing active ingredients, indicating good stability.

[0106] Example 6

[0107] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0108] 1) Weigh 5 parts myristate, 2 parts hexadecane, 2 parts tocopheryl acetate, 1.5 parts laurocapramone, 0.1 parts propylparaben, 4 parts polyoxyethylene 40 hydrogenated castor oil, and 4 parts triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0109] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0110] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 1000 rpm, and maintain the circulation flow rate at 100 ml / min for 20 min of emulsification. Then turn off the rotating bed to obtain VE nanoemulsion.

[0111] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts hydroquinone and 0.5 parts sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0112] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 128.19 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0113] Example 7

[0114] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0115] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 3 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0116] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0117] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0118] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts ascorbate glucoside and 1 part sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0119] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 122.96 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0120] Example 8

[0121] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0122] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0123] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0124] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 1500 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0125] 4) Pour the obtained VE nanoemulsion into a brown three-necked flask, cool to 45°C, weigh out 2 parts hydroquinone and 0.5 parts sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0126] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 112.09 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0127] Example 9

[0128] A method for preparing a whitening and freckle-removing nano-cream using supergravity technology includes the following steps:

[0129] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopheryl acetate, 1.5 parts of laurocapramone, 0.1 parts of propylparaben, 4 parts of Tween 80, and 4 parts of triglyceride monostearate and place them in a three-necked flask. Then heat the mixture in a water bath at 65°C until homogeneous, and use this mixture as the oil phase.

[0130] 2) Weigh 20 parts of glycerin, 0.2 parts of methylparaben, 0.06 parts of sodium dodecyl sulfate, and the remainder of deionized water, totaling 100 parts. Place them in a beaker, then heat in a water bath at 65°C until they are mixed evenly, and use this as the aqueous phase.

[0131] 3) Add the oil phase and aqueous phase to a jacketed flask, connect the flask to a rotating packed bed and a circulating water bath, and maintain the temperature at 65℃; start the centrifugal rotating packed bed, rotate at 2000 rpm, and the circulation flow rate is 150 ml / min. Circulate and emulsify for 15 min, then turn off the rotating bed to obtain VE nanoemulsion.

[0132] 4) Pour the obtained VE nanoemulsion into a three-necked flask, cool to 45°C, weigh out 3 parts of tranexamic acid and 0.5 parts of sodium metabisulfite, add them to the VE nanoemulsion, stir at 500 rpm until cooled to room temperature, and you will get the whitening and freckle-removing nanoemulsion cream.

[0133] The whitening and freckle-removing nano-cream prepared in this embodiment is a milky white paste with an average particle size of 121.17 nm and a relatively uniform distribution. Long-term stability testing showed that after storage at room temperature, 4℃, and 40℃ for 90 days, there were no significant changes in appearance, particle size, or the content of whitening and freckle-removing active ingredients, indicating good stability.

[0134] Comparative Example 1

[0135] Repeat Example 1, except that:

[0136] Instead of using a high-gravity rotating packed bed, a conventional stirring paddle was used for agitation. Other conditions and specific operating procedures were exactly the same as in Example 1.

[0137] The results showed that the average particle size of the prepared whitening and freckle-removing nano-cream was 258.08 nm, which was three times that of Example 1, and the particle size uniformity was poor. Compared with ordinary reactors, the high-gravity rotating packed bed can effectively reduce the size of the cream and improve its uniformity.

[0138] Comparative Example 2

[0139] Repeat Example 2, except that:

[0140] In step 4), 0.1 parts of sodium metabisulfite were added. All other conditions and specific operating procedures were exactly the same as in Example 2.

[0141] The results showed that the hydroquinone in the whitening and spot-removing nano-cream oxidized, changing its appearance from milky white to brownish-red. Adding less than 0.5 parts of antioxidant is insufficient to protect the active ingredients, and the optimal amount of antioxidant in skincare products is less than 1%. Therefore, the antioxidant content in this formula is 0.5%-1%.

[0142] Comparative Example 3

[0143] Repeat Example 2, except that:

[0144] In step 4), the antioxidant is tert-butyl-p-cresol. All other conditions and specific operating procedures are completely consistent with Example 2.

[0145] The results showed that the whitening and freckle-removing nano-cream turned light brown in about 10 days. The antioxidant effect of tert-butyl-p-cresol was not as strong as that of sodium metabisulfite and anhydrous sodium sulfite in this formula.

[0146] Comparative Example 4

[0147] Repeat Example 2, except that:

[0148] In step 4), the antioxidant is anhydrous sodium sulfite. All other conditions and specific operating procedures are completely consistent with Example 2.

[0149] The results showed that the average particle size of the prepared whitening and freckle-removing nano-cream was 113.17 nm, slightly larger than that obtained using sodium metabisulfite as an antioxidant, but with comparable antioxidant capacity. Long-term stability tests showed no significant changes in appearance, particle size, or content of whitening and freckle-removing active ingredients after 90 days of storage at room temperature, 4℃, and 40℃, indicating good stability. Therefore, anhydrous sodium metabisulfite is also suitable as an antioxidant for nano-cream systems.

[0150] Comparative Example 5

[0151] Repeat Example 1, except that:

[0152] In step 1), add 2 parts of an oil-in-water emulsifier: polyoxyethylene 40 hydrogenated castor oil, and 1 part of an oil-in-water emulsifier: triglyceride monostearate. Other conditions and specific operating steps are completely consistent with those in Example 1.

[0153] The results showed that the average particle size of the prepared whitening and freckle-removing nano-emulsion cream was 155.21 nm, twice that of Example 1, and the particle size uniformity was poor. Furthermore, leakage of active ingredients, not encapsulated in the nano-droplets, was observed in the transmission image. This was attributed to insufficient emulsifier addition and poor emulsification effect.

[0154] Comparative Example 6

[0155] Repeat Example 1, except that:

[0156] In step 1), add 8 parts of an oil-in-water emulsifier: polyoxyethylene 40 hydrogenated castor oil, and 4 parts of an oil-in-water emulsifier: triglyceride monostearate. Other conditions and specific operating steps are completely consistent with those in Example 1.

[0157] The results showed that the prepared whitening and freckle-removing nano-cream did not exhibit regularly shaped round nanodroplets in the transmission spectrum, and aggregates were present. Oil-water separation occurred after a certain storage time. Excessive emulsifier addition led to micelle formation, affecting the texture and stability of the cream.

[0158] Comparative Example 7

[0159] Repeat Examples 2 and 3, except that:

[0160] In step 1), add 4 parts of oil-in-water emulsifier: polyoxyethylene-21 stearyl alcohol ether, and 4 parts of water-in-oil emulsifier: polyoxyethylene-2 ​​stearyl alcohol ether. Other conditions and specific operating steps are completely consistent with those in Examples 2 and 3.

[0161] The results showed that the prepared whitening and freckle-removing nano-cream had a particle size of 191.44 nm, which was 2.5 times and 2 times larger than those in Examples 2 and 3, respectively. This indicates that the emulsifying effect of the combination of polyoxyethylene-21 stearyl alcohol ether and polyoxyethylene-2 ​​stearyl alcohol ether is not as good as the combination of polyoxyethylene 40 hydrogenated castor oil with triglyceride monostearate and Tween 80 with triglyceride monostearate. Appropriate combinations of oil-in-water and water-in-oil emulsifiers can effectively reduce the particle size.

[0162] Comparative Example 8

[0163] Repeat Example 1, except that:

[0164] In step 1), add 2 parts of an oil-in-water emulsifier: hydrogenated castor oil with polyethylene oxide 40, and 6 parts of an oil-in-water emulsifier: triglyceride monostearate. Other conditions and specific operating steps are completely consistent with those in Example 1.

[0165] The results showed that the prepared whitening and freckle-removing nano-cream had a particle size of 188.42 nm, which was 2.4 times that of Example 1. The product also had a higher viscosity and was less refined than the product obtained in Example 1, resulting in a poorer skin feel. This is because triglyceride monostearate is a solid emulsifier, and its high proportion leads to increased system viscosity and hardness. This indicates that the ratio of water-in-oil emulsifier to oil-in-water emulsifier has a significant impact on particle size. A suitable ratio not only reduces the cream's particle size but also improves its texture and skin feel.

[0166] Comparative Example 9

[0167] Repeat Example 1, except that:

[0168] In step 3), the cyclic emulsification time is 5 minutes, and other conditions and specific operating steps are completely consistent with those in Example 1.

[0169] The results showed that if the emulsification time was too short, the particle size would be uneven and the morphology would be irregular. A suitable emulsification time can achieve a better emulsification effect, while an excessively long emulsification time is a waste of energy and resources. The present invention can achieve a very good effect at around 15-20 minutes.

[0170] Comparative Example 10

[0171] Repeat Example 1, except that:

[0172] In step 1), no hexadecane is added. All other conditions and specific operating procedures are exactly the same as in Example 1.

[0173] The results showed that the prepared whitening and freckle-removing nano-cream was a white flocculent substance with layering. Solid oils can give the product a certain appearance, making it tend to solidify, and also play a certain stabilizing role. This invention uses a combination of solid-phase and liquid-phase oils to give the product a suitable viscosity, avoiding the problem of too short a skin contact time due to an excessively thin product, and also avoiding the problem of clumping and poor skin feel due to an excessively high viscosity.

[0174] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is impossible to exhaustively list all embodiments here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A whitening and freckle-removing nano-cream, characterized in that, The raw materials include the following parts by weight: 2-5 parts of oil-in-water emulsifier, 2-5 parts of water-in-oil emulsifier, 3-5 parts of liquid oil, 1-3 parts of solid oil, 1-3 parts of tocopheryl acetate, 0.5-2 parts of laurocapram, 0.1-0.25 parts of propylparaben, 10-30 parts of glycerin, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium lauryl sulfate, 0.5-1 part of antioxidant, 1.8-4 parts of whitening and spot-removing active ingredients, and deionized water added to a total of 100 parts; The oil-in-water emulsifier is selected from one or more of Tween 80, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene-21 stearyl ether, and polyglycerol-10 laurate. The water-in-oil emulsifier is selected from one or more of the following: triglyceride monostearate, Span 6, polyoxyethylene-2 ​​stearyl alcohol ether, and stearic acid. The ratio of the water-in-oil emulsifier to the oil-in-water emulsifier is 1:3-3:1; The liquid oil is one or more of polydimethylsiloxane, caprylic / capric glyceride, myristate, and palm oil; The solid fat is one or more of hexadecane, octadecane, and paraffin; The antioxidant is sodium metabisulfite, anhydrous sodium sulfite, or one or more of these. The method for preparing the whitening and freckle-removing nano-cream using supergravity technology is characterized by comprising the following steps: 1) Weigh 2-5 parts of oil-in-water emulsifier, 2-5 parts of water-in-oil emulsifier, 3-5 parts of liquid oil, 1-3 parts of solid oil, 1-3 parts of tocopheryl acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath while stirring until homogeneous to obtain the oil phase; 2) Weigh out 10-30 parts of glycerin, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium dodecyl sulfate, and an appropriate amount of deionized water, and heat and stir evenly in a water bath to obtain an aqueous phase; 3) Add the oil phase and water phase to the jacketed flask, connect the flask to the centrifugal rotating packed bed and a circulating water bath, and maintain the temperature at the same temperature as in steps 1) and 2); start the centrifugal rotating packed bed, and the oil and water phases circulate and emulsify between the centrifugal rotating packed bed and the jacketed reactor. The droplets collide violently in the centrifugal environment and are repeatedly mixed and sheared to obtain VE nanoemulsion. 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool it to a certain temperature, then add 1.8-4 parts of finely ground whitening and spot-removing active ingredients and 0.5-1 parts of antioxidant, stir until cooled to room temperature, and you will get the whitening and spot-removing nanoemulsion cream.

2. The whitening and freckle-removing nano-cream according to claim 1, characterized in that: The whitening and freckle-removing active ingredients are one or more of glycyrrhizin, hydroquinone, α-arbutin, nicotinamide, ascorbyl glucoside, and tranexamic acid.

3. The whitening and freckle-removing nano-cream according to claim 1, characterized in that: The water bath heating temperature in steps 1), 2), and 3) is 60-80℃; In step 3), the emulsification cycle takes 10-20 minutes. In step 3), the circulation flow rate of the circulating emulsification is 50-150 ml / min; In step 3), the rotational speed of the rotary filling bed is 1000-2500 rpm; In step 4), the specified temperature is 30-45℃; In step 4), the stirring speed is 300-500 rpm.

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