Skin-whitening and freckle-removing nano cream and preparation method of skin-whitening and freckle-removing nano cream by supergravity technology

Abstract

The invention discloses a whitening and freckle-removing nano cream cream and a supergravity technology preparation method, the whitening and freckle-removing nano cream cream comprises the following raw materials by weight: 2-5 parts of an oil-in-water emulsifier, 2-5 parts of a water-in-oil emulsifier, 3-5 parts of liquid grease, 1-3 parts of solid grease, 1-3 parts of tocopheryl acetate, and 0.5-2 parts of laurocapram. The whitening and freckle-removing mask is prepared from the following raw materials in parts by weight: 0.1-0.25 part of propyl hydroxybenzoate, 10-30 parts of glycerol, 0.2-0.3 part of methylparaben, 0.05-0.1 part of lauryl sodium sulfate, 0.5-1 part of an antioxidant, 1.8-4 parts of whitening and freckle-removing active ingredients and the balance of deionized water which is added until the total amount is 100 parts. The invention further discloses a preparation method of the whitening and freckle-removing nano cream. The particle size of the whitening and freckle-removing nano-cream is 70-130 nm, and the appearance, the particle size and the whitening and freckle-removing active ingredient content are not obviously changed under the conditions that the whitening and freckle-removing nano-cream is stored at normal temperature, 40 DEG C and 4 DEG C for more than or equal to 90 days respectively.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and in particular relates to a whitening and freckle-removing nano cream and a supergravity technology preparation method. Background Art

[0002] The formation of pigmentation is due to the presence of melanocyte progenitor cells in the basal layer of the skin. When affected by internal and external factors, they release tyrosinase and form melanin particles under a series of catalytic effects. When there is a steady stream of melanin aggregated in the epidermis, pigmentation will form. The basal layer of the skin is located at the bottom layer of the epidermis, and it is difficult for drugs to pass through the stratum corneum to reach the basal layer of the skin, so they cannot effectively exert their therapeutic effects. The application of nano transdermal drug delivery technology in the treatment of pigmentation can significantly improve the treatment effect, reduce irritation, and improve the stability of active ingredients.

[0003] A new type of multi-drug delivery system, nanoemulsion, can simultaneously load fat-soluble drugs and water-soluble drugs, and can also increase the solubility of poorly soluble drugs, with sustained release and targeting effects. In addition, nanoemulsions are superior to liposomes in terms of amplification and stability, are easy to industrialize, and have less toxicity than liposomes. Compared with ordinary emulsions, micelles or suspensions, they have higher thermodynamic stability, thereby extending the shelf life. However, nanoemulsions are limited by their low viscosity, resulting in low residence time and spreadability. Cream systems have higher viscosity than emulsions, and have higher skin residence time and spreadability, so nano-scale creams have great advantages in skin care and treatment of skin diseases.

[0004] Tsujimoto H et al. found in a skin permeability experiment that particles with a size of ≤200 nm can penetrate the skin pores and stratum corneum and reach the basal layer of the skin (Tsujimoto H, Hara K. Development of functional skin care cosmetics 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 separate heating of the water and oil phases, two-step homogenization, membrane filtration and subsequent stirring. The process is relatively complex and time-consuming, and is not easy to industrialize.

[0006] Chinese patent application CN 104382801A discloses a nanoemulsion and gel for whitening and removing freckles. The particle size of the liquid nanoemulsion is between 70-100 nm, and then it is made into a gel to improve its skin adhesion and residence time. 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] Combinations of ingredients with similar effects can play a synergistic role and can also reduce the amount of related ingredients added. For example, hydroquinone as a skin depigmenting agent has a certain irritation. The state has relevant regulations on drugs containing hydroquinone. The maximum content of hydroquinone in over-the-counter drugs is 2%, and the content of hydroquinone in prescription drugs is 4%. The method of combined drug treatment can be used to reduce the dosage of hydroquinone and improve the treatment effect. Vitamin E is a fat-soluble vitamin with antioxidant, moisturizing and antipruritic effects. It can be used to assist in the treatment of diseases such as chloasma and freckles. Some doctors suggest that hydroquinone cream and vitamin E cream can be used to treat pigmentation. Hydroquinone cream can effectively reduce the number and volume of subcutaneous pigment cells, thereby achieving a whitening effect. Vitamin E cream is a very strong antioxidant that can fight free radicals to achieve the effect of whitening the skin and removing pigmentation. Therefore, vitamin E and hydroquinone are combined to make a whitening and freckle-removing nano cream. The two drugs work together to remove freckles and improve the treatment effect.

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

[0009] The first technical problem to be solved by the present invention is to provide a whitening and freckle-removing nano cream. The nano cream has a small particle size, good transdermal effect, high stability and low irritation. The particle size of the whitening and freckle-removing nano cream of the present invention is between 70-130nm. When stored for ≧90 days at room temperature, 40°C and 4°C, there is no significant change in appearance, particle size and content of whitening and freckle-removing active ingredients. Ultra-gravity technology makes it possible to nano-size hydroquinone cream. Ultra-gravity technology is to strengthen the multiphase flow transmission and reaction process. In this process, the liquid is dispersed and broken by the filler under strong centrifugal force, and the surface area is continuously renewed to achieve the effect of high dispersion, high turbulence and strong mixing. The advantages of this technology are as follows: small product particle size, small equipment volume, low energy consumption, simple operation, low cost, safe and flexible, easy to scale up, and thus suitable for industrial production.

[0010] The second technical problem to be solved by the present invention is to provide a method for preparing a whitening and freckle-removing nano cream using ultra-gravity technology. The preparation method has a simple process, low cost, is easy to scale up, and is suitable for industrial production.

[0011] In order to solve the above-mentioned first technical problem, the present invention adopts the following technical solution:

[0012] A whitening and freckle-removing nano cream comprises the following raw materials 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 alcohol ether, and polyglyceryl-10 laurate.

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

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

[0018] Preferably, the liquid oil is one or more of dimethicone, caprylic / capric glyceride, myristic acid ester, and palm oil.

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

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

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

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

[0023] A method for preparing a whitening and freckle-removing nano cream using ultra-gravity technology comprises 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 tocopherol acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath and stir to obtain an oil phase;

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

[0026] 3) adding the oil phase and the water phase into the jacketed flask, connecting the flask and the high gravity rotating packed bed to a circulating water bath, and maintaining the temperature at the same temperature as in steps 1) and 2); starting the high gravity rotating packed bed, the oil and water phases circulate and emulsify between the high gravity rotating packed bed and the jacketed reactor, the droplets collide violently in the high gravity environment, and are repeatedly mixed and sheared to obtain a VE nanoemulsion;

[0027] 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool to a certain temperature, add 1.8-4 parts of finely ground whitening and anti-freckle active ingredients and 0.5-1 parts of antioxidants, and stir until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

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

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

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

[0031] Preferably, in step 3), the rotating speed of the rotating packed bed is 1000-2500 rpm.

[0032] Preferably, in step 4), the certain temperature is 30-45°C.

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

[0034] Any range described in the present invention includes the end value and any numerical value between the end values ​​and any sub-range formed by the end value or any numerical value between the end values.

[0035] Unless otherwise specified, all raw materials in the present invention can be purchased from the market, and the equipment used in the present invention can adopt conventional equipment in the relevant field or refer to the 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 the particle size of the traditional cream. The appearance, particle size, and content of whitening and freckle-removing active ingredients do not change significantly when stored at room temperature, 40°C, and 4°C for ≥90 days, and the stability is good;

[0038] 2. The preparation method of the present invention utilizes ultra-gravity technology to intensify the process. Compared with the traditional emulsification method, it significantly shortens the emulsification time, thereby shortening the production cycle. It has high efficiency, low cost, and is very easy to scale up, thereby achieving the invention goal of industrial production.

[0039] 3. Combine the strong antioxidant vitamin E with skin fading ingredients or whitening ingredients to achieve the effects of fighting free radicals, whitening the skin, removing and improving spots, and can also reduce the amount of irritating active substances added, reduce irritation, and improve the treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

[0042] Figure 2 The transmission electron microscope 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 physical picture of the whitening and freckle-removing nano cream prepared in Example 1;

[0044] Figure 4 This is a graph showing changes in the content of the whitening and anti-freckle active ingredient in the whitening and anti-freckle nano cream prepared in Example 1 after being left at room temperature, 40° C., and 4° C. for 90 days.

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

[0046] Figure 6 This is a physical picture of the whitening and freckle-removing nano cream prepared in Comparative Example 2;

[0047] Figure 7 This is a transmission electron microscope image of the whitening and freckle-removing nano cream prepared in Comparative Example 5;

[0048] Figure 8 This is a transmission electron microscopy image of the whitening and freckle-removing nano cream prepared in Comparative Example 6; DETAILED DESCRIPTION

[0049] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

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

[0051]

[0052] According to some 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 alcohol ether, and polyglyceryl-10 laurate.

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

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

[0055] According to some embodiments of the present invention, the liquid oil is one or more of dimethicone, caprylic / capric glyceride, myristic acid ester, and palm oil.

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

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

[0058] According to some embodiments of the present invention, the whitening and freckle-removing active ingredient is one or more of glabridin, hydroquinone, α-arbutin, niacinamide, ascorbyl glucoside, and tranexamic acid.

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

[0060] A method for preparing a whitening and freckle-removing nano cream comprises 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 tocopherol acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath and stir to obtain an oil phase;

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

[0063] 3) adding the oil phase and the water phase into the jacketed flask, connecting the flask and the rotating packed bed to a circulating water bath, and maintaining the temperature at the same temperature as in steps 1) and 2); starting the high-gravity rotating packed bed, and circulating the oil-water phases between the high-gravity rotating packed bed and the jacketed reactor for emulsification, and the droplets collide violently in the high-gravity environment, and are repeatedly mixed and sheared to obtain a VE nanoemulsion;

[0064] 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool to a certain temperature, add 1.8-4 parts of finely ground whitening and anti-freckle active ingredients and 0.5-1 parts of antioxidants, and stir until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

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

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

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

[0068] According to certain embodiments of the present invention, in step 3), the rotating speed of the rotating packed 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 ultra-gravity technology comprises the following steps:

[0073] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol 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 monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain an oil phase;

[0074] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0075] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed at a speed of 2000 rpm and a circulation flow rate of 150 ml / min, circulate and emulsify for 15 minutes, and 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 2 parts of glabridin and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and freckle-removing nanoemulsion.

[0077] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0078] Example 2

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

[0080] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 4 parts of polyoxyethylene 40 hydrogenated castor oil, and 4 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain the oil phase;

[0081] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0082] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed at a speed of 2000 rpm and a circulation flow rate of 150 ml / min, circulate and emulsify for 15 minutes, and 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 2 parts of hydroquinone and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and freckle-removing active ingredients did not change significantly, and the stability was good.

[0085] Example 3

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

[0087] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 4 parts of Tween 80, and 4 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain the oil phase;

[0088] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0089] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed at a speed of 2000 rpm and a circulation flow rate of 150 ml / min, circulate and emulsify for 15 minutes, and 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 2 parts of hydroquinone and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[0091] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0092] Example 4

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

[0094] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to prepare the oil phase;

[0095] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0096] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed, with a rotation speed of 2500 rpm and a circulation flow rate of 100 ml / min, circulate emulsification for 15 min, and close 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 2 parts of α-arbutin and 0.5 parts of sodium metabisulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[0098] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0099] Example 5

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

[0101] 1) Weigh 5 parts of caprylic acid glyceride, 1 part of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 4 parts of polyoxyethylene 40 hydrogenated castor oil, and 4 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 75° C. and mix well to obtain the oil phase;

[0102] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, with a total of 100 parts, put them in a beaker, and then heat them in a water bath at 75° C. and mix them evenly to form the aqueous phase;

[0103] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 75°C; start the ultra-gravity rotating packed bed, with a rotation speed of 2000 rpm and a circulation flow rate of 100 ml / min, circulate emulsification for 15 min, and close 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 2 parts of hydroquinone and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[0105] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0106] Example 6

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

[0108] 1) Weigh 5 parts of myristic acid ester, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 4 parts of polyoxyethylene 40 hydrogenated castor oil, and 4 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain the oil phase;

[0109] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0110] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed, with a rotation speed of 1000 rpm and a circulation flow rate of 100 ml / min, circulate emulsification for 20 min, and close 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 2 parts of hydroquinone and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[0112] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0113] Example 7

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

[0115] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 3 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain the oil phase;

[0116] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0117] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed at a speed of 2000 rpm and a circulation flow rate of 150 ml / min, circulate and emulsify for 15 minutes, and 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 2 parts of ascorbyl glucoside and 1 part of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and freckle-removing active ingredients did not change significantly, and the stability was good.

[0120] Example 8

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

[0122] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 5.5 parts of Tween 80, and 2.5 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to prepare the oil phase;

[0123] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0124] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed, with a rotation speed of 1500 rpm and a circulation flow rate of 150 ml / min, circulate emulsification for 15 min, and close 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 2 parts of hydroquinone and 0.5 parts of sodium pyrosulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[0126] The whitening and anti-freckle 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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, and the stability was good.

[0127] Example 9

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

[0129] 1) Weigh 5 parts of polydimethylsiloxane, 2 parts of hexadecane, 2 parts of tocopherol acetate, 1.5 parts of laurocapram, 0.1 parts of propylparaben, 4 parts of Tween 80, and 4 parts of monostearate triglyceride into a three-necked flask, and then heat in a water bath at 65° C. and mix well to obtain the oil phase;

[0130] 2) Weigh 20 parts of glycerol, 0.2 parts of methylparaben, 0.06 parts of sodium lauryl sulfate, and the rest of deionized water, a total of 100 parts, put them in a beaker, and then heat them in a water bath at 65° C. and mix them evenly to form the aqueous phase;

[0131] 3) Add the oil phase and the water phase into the jacketed flask, connect the flask and the rotating packed bed to a circulating water bath, and maintain the temperature at 65°C; start the ultra-gravity rotating packed bed at a speed of 2000 rpm and a circulation flow rate of 150 ml / min, circulate and emulsify for 15 minutes, and 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 3 parts of tranexamic acid and 0.5 parts of sodium metabisulfite, add them to the VE nanoemulsion, and stir at 500 rpm until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

[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. After long-term stability testing, it was found that after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and freckle-removing active ingredients did not change significantly, and the stability was good.

[0134] Comparative Example 1

[0135] Repeat Example 1, except that:

[0136] The supergravity rotating packed bed was not used but a common stirring paddle was used for stirring. Other conditions and specific operation steps were completely consistent with those in Example 1.

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

[0138] Comparative Example 2

[0139] Repeat Example 2, except that:

[0140] In step 4), 0.1 parts of sodium pyrosulfite are added. Other conditions and specific operation steps are exactly the same as those in Example 2.

[0141] The results show that the hydroquinone in the whitening and anti-freckle nano cream is oxidized and its appearance is no longer milky white, but brown. If the antioxidant is added in an amount less than 0.5 parts, it cannot protect the active ingredients. The amount of antioxidant added in skin care products is preferably less than 1%, so the amount of antioxidant added 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. Other conditions and specific operation steps are exactly the same as those in Example 2.

[0145] The results showed that the whitening and anti-freckle nano cream turned light brown in about 10 days. The antioxidant effect of tert-butyl-p-cresol was not as good as that of sodium pyrosulfite 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. Other conditions and specific operation steps are exactly the same as those in Example 2.

[0149] The results showed that the average particle size of the whitening and anti-freckle nano cream was 113.17 nm, which was slightly larger than that of the one using sodium metabisulfite as an antioxidant, but the antioxidant capacity was comparable. After long-term stability testing, after being stored at room temperature, 4°C, and 40°C for 90 days, the appearance, particle size, and content of whitening and anti-freckle active ingredients did not change significantly, indicating good stability. Therefore, anhydrous sodium sulfite is also suitable as an antioxidant for nano cream systems.

[0150] Comparative Example 5

[0151] Repeat Example 1, except that:

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

[0153] The results show that the average particle size of the whitening and anti-freckle nano cream is 155.21 nm, which is twice that of Example 1, and the particle size uniformity is poor. In the transmission image, it can be seen that the active ingredients have leaked and are not wrapped in the nanoemulsion droplets. The reason is that the amount of emulsifier added is small and the emulsification effect is poor.

[0154] Comparative Example 6

[0155] Repeat Example 1, except that:

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

[0157] The results showed that the whitening and anti-freckle nano cream did not have regular round nanoemulsion droplets in the transmission image, and agglomerates appeared. After a certain period of storage, oil and water separation occurred. Too much emulsifier added formed micelles and affected the texture and stability of the cream.

[0158] Comparative Example 7

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

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

[0161] The results show that the particle size of the whitening and freckle-removing nano cream is 191.44 nm, which is 2.5 times and 2 times that of Examples 2 and 3, respectively. This indicates that the emulsification 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 and monostearic triglyceride, Tween 80 and monostearic triglyceride, and the appropriate combination of water-in-oil and oil-in-water emulsifiers can effectively reduce the particle size.

[0162] Comparative Example 8

[0163] Repeat Example 1, except that:

[0164] In step 1), 2 parts of water-in-oil emulsifier: polyoxyethylene 40 hydrogenated castor and 6 parts of water-in-oil emulsifier: monostearate triglyceride were added. Other conditions and specific operation steps were completely consistent with those in Example 1.

[0165] The results show that the particle size of the whitening and freckle-removing nano cream is 188.42 nm, which is 2.4 times that of Example 1, and the product viscosity is relatively large, which is not as delicate as the product obtained in Example 1, and the skin feel is poor, because monostearate triglyceride is a solid emulsifier, and its large proportion will lead to increased viscosity and hardness of the system. It shows that the ratio of water-in-oil emulsifier to water-in-oil emulsifier has a great influence on the particle size. The appropriate ratio will not only reduce the particle size of the cream, but also improve the texture and skin feel of the cream.

[0166] Comparative Example 9

[0167] Repeat Example 1, except that:

[0168] In step 3), the circulating emulsification time is 5 min, and other conditions and specific operation steps are exactly the same as those in Example 1.

[0169] The results show that if the emulsification time is too short, the particle size is uneven and the morphology is irregular. A suitable emulsification time can achieve a better emulsification effect. A long emulsification time is a waste of energy and resources. The present invention can achieve a good effect within about 15-20 minutes.

[0170] Comparative Example 10

[0171] Repeat Example 1, except that:

[0172] In step 1), hexadecane is not added. Other conditions and specific operation steps are completely consistent with those in Example 1.

[0173] The results show that the whitening and freckle-removing nano cream is a white flocculent with stratification. Solid grease can give the product a certain appearance, making the product tend to solidify and also play a certain stabilizing role. The present invention uses a combination of solid-phase grease and liquid-phase grease to make the product have a suitable viscosity, which not only avoids the problem of too short skin residence time caused by too thin products, but also avoids the situation of too high viscosity, agglomeration and poor skin feel.

[0174] Obviously, the above embodiments of the present invention are merely examples for clearly explaining the present invention, and are not intended to limit the implementation methods of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all implementation methods here. Any obvious changes or modifications derived from the technical solution of the present invention are still within the scope of protection of the present invention.

Claims

1. A whitening and freckle-removing nano cream, characterized in that: The invention comprises the following raw materials in parts by weight:

2. The whitening and freckle-removing nano cream according to claim 1, characterized in that: The water-in-oil emulsifier is selected from one or more of Tween 80, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene-21 stearyl alcohol ether, and polyglyceryl-10 laurate.

3. The whitening and freckle-removing nano cream according to claim 1, characterized in that: The water-in-oil emulsifier is selected from one or more of monostearate triglyceride, Span 6, polyoxyethylene-2 ​​stearyl alcohol ether, and stearic acid.

4. The whitening and freckle-removing nano cream according to claim 1, characterized in that: The ratio of the oil-in-water emulsifier to the water-in-oil emulsifier is 1:3-3:

1.

5. The whitening and freckle-removing nano cream according to claim 1, characterized in that: Preferably, the liquid oil is one or more of dimethicone, caprylic / capric glyceride, myristic acid ester, and palm oil.

6. The whitening and freckle-removing nano cream according to claim 1, characterized in that: The solid oil is one or more of hexadecane, octadecane and paraffin.

7. The whitening and freckle-removing nano cream according to claim 1, characterized in that: The antioxidant is one or more of sodium pyrosulfite and anhydrous sodium sulfite.

8. 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 glabridin, hydroquinone, α-arbutin, niacinamide, ascorbyl glucoside, and tranexamic acid.

9. The method for preparing a whitening and anti-freckle nano cream by ultra-gravity technology according to any one of claims 1 to 8, characterized in that: The steps include: 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 tocopherol acetate, 0.5-2 parts of laurocapram, and 0.1-0.25 parts of propylparaben, and heat in a water bath and stir to obtain an oil phase; 2) Weigh 10-30 parts of glycerol, 0.2-0.3 parts of methylparaben, 0.05-0.1 parts of sodium lauryl sulfate, and an appropriate amount of deionized water, and heat and stir in a water bath to obtain an aqueous phase; 3) adding the oil phase and the water phase into the jacketed flask, connecting the flask and the high gravity rotating packed bed to a circulating water bath, and maintaining the temperature at the same temperature as in steps 1) and 2); starting the high gravity rotating packed bed, the oil and water phases circulate and emulsify between the high gravity rotating packed bed and the jacketed reactor, the droplets collide violently in the high gravity environment, and are repeatedly mixed and sheared to obtain a VE nanoemulsion; 4) Pour the VE nanoemulsion obtained in step 3) into a flask, cool to a certain temperature, add 1.8-4 parts of finely ground whitening and anti-freckle active ingredients and 0.5-1 parts of antioxidants, and stir until cooled to room temperature to obtain a whitening and anti-freckle nanoemulsion.

10. The preparation method according to claim 9, characterized in that: The water bath heating temperature in step 1), step 2) and step 3) is 60-80°C; Preferably, in step 3), the cyclic emulsification time is 10-20 min; Preferably, in step 3), the circulation flow rate of the cyclic emulsification is 50-150 ml / min; Preferably, in step 3), the rotating speed of the rotating packed bed is 1000-2500 rpm; Preferably, in step 4), the certain temperature is 30-45°C; Preferably, in step 4), the stirring speed is 300-500 rpm.

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