Pre-nanoemulsion capable of being used for encapsulating oil-soluble functional substances as well as preparation method and application of pre-nanoemulsion

Abstract

The invention relates to a pre-nanoemulsion capable of being used for encapsulating an oil-soluble functional substance as well as a preparation method and application of the pre-nanoemulsion. The pre-nanoemulsion is mainly prepared from the following raw materials in percentage by mass: a phase A: 5-20% of first grease, 1-2% of lecithin and 0.01-0.1% of an antioxidant; the phase B comprises the following components in percentage by weight: 2%-7% of a nonionic surfactant, 2%-7% of polyhydric alcohol and 63.9%-89.99% of water; the nonionic surfactant is one or more of tween-80, stearyl alcohol polyether-21, glyceryl polyether-26, beheneth-25 and polyglycerol-10 myristate, and the nonionic surfactant is one or more of polysorbate-80, stearyl alcohol polyether-21, glyceryl polyether-26, beheneth-25 and polyglycerol-10 The pre-nanoemulsion can improve the stability of the oil-soluble functional components, can wrap various oil-soluble functional substances, can further obtain the nanoemulsion wrapped with the oil-soluble functional raw materials, and both the pre-nanoemulsion and the nanoemulsion can be applied to cosmetics.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanoemulsions, and particularly relates to a pre-nanoemulsion capable of encapsulating oil-soluble active substances, a preparation method thereof, and an application thereof. Background Art

[0002] Nanoemulsion is one of the best carriers for promoting the penetration and transportation of active ingredients in the skin. Nanoemulsion refers to a multiphase colloidal dispersion system in which one phase is highly dispersed in another immiscible phase in the form of nanoscale droplets by using appropriate surfactants or external conditions, and the droplet size is usually distributed between 50 and 500 nm. Nanoemulsion is a novel drug delivery system with great potential, which can effectively encapsulate functional ingredients into droplets, and has the characteristics of large specific surface area, kinetic stability, thermodynamic instability, improving the stability of encapsulated drugs, increasing the solubility of poorly soluble drugs, increasing the bioavailability of macromolecular water-soluble drugs, and drug sustained-release effect. Compared with traditional delivery systems, nanoemulsion can improve the water solubility of lipophilic active compounds, and can also inhibit phenomena such as floating, sedimentation, and delamination of emulsions caused by gravity, thereby ensuring the long-term physical stability of emulsions.

[0003] Nanoemulsion has the advantages of high encapsulation efficiency, low turbidity, high stability, and diversity of preparation methods. Compared with other drug delivery systems such as liposomes, nanoemulsion has smaller emulsion particle size, finer system, more stable physical and chemical properties, and better skin feel. However, applying nanoemulsion to the cosmetic field still faces many challenges. Traditional nanoemulsion technologies all encapsulate a single substance and cannot be applied to different oil-soluble components.

[0004] In addition, how to design and simply prepare nanoemulsion with high stability and high encapsulation efficiency is a challenge faced by current nanoemulsion technologies. Traditional nanoemulsion production methods need to conduct single-factor or orthogonal experiments on the nanoemulsion formula and production parameters according to the characteristics of the encapsulated active substances to determine the final preparation method. This process often requires staff with R & D experience and a long R & D cycle, which is often difficult for some small raw material preparation companies to achieve. Moreover, for the various oil-soluble active substances on the market, continuously changing production methods and parameters in production also increases production costs.

[0005] In summary, there is an urgent need in the industry to provide a nanoemulsion that can be used to encapsulate different oil-soluble active substances and has a simple preparation method, so as to broaden the application of nanoemulsion in the cosmetic field and achieve better economic benefits. Summary of the Invention

[0006] Based on this, the object of the present invention is to provide a pre-nanoemulsion that can improve the stability of oil-soluble active ingredients and can encapsulate a variety of oil-soluble active substances, and further obtain a nanoemulsion loaded with oil-soluble active raw materials, and both the pre-nanoemulsion and the nanoemulsion can be applied to cosmetics.

[0007] The technical solution is as follows:

[0008] A pre-nanoemulsion that can be used to encapsulate oil-soluble active substances is mainly made of raw materials in the following mass percentages:

[0009] Phase A:

[0010] The first oil 5% - 20%,

[0011] Lecithin 1% - 2%,

[0012] Antioxidant 0.01% - 0.1%.

[0013] Phase B:

[0014] Non-ionic surfactant 2% - 7%,

[0015] Polyol 2% - 7%,

[0016] Water 63.9% - 89.99%.

[0017] The non-ionic surfactant is one or more of Tween-80, Stearyl alcohol polyether-21, Glycerin polyether-26, Behenyl alcohol polyether-25, and Polyglyceryl-10 myristate.

[0018] In one embodiment, the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances is mainly made of raw materials in the following mass percentages:

[0019] Phase A:

[0020] The first oil 10% - 20%,

[0021] Lecithin 1% - 2%,

[0022] Antioxidant 0.01% - 0.05%.

[0023] Phase B:

[0024] Non-ionic surfactant 2% - 5%,

[0025] Polyol 4% - 7%,

[0026] Water 65.95% - 89.99%.

[0027] In one embodiment, the first oil is one or more of triglyceride caprylic / capric acid, evening primrose oil, octyldodecanol, and isopropyl myristate.

[0028] In one embodiment, the lecithin is PC50 soy lecithin.

[0029] In one embodiment, the antioxidant is pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate).

[0030] In one embodiment, the polyol is one or more of glycerol and pentanediol.

[0031] In one embodiment, the raw material further contains a preservative.

[0032] In one embodiment, the preservative is a mixture of p-hydroxyacetophenone and pentanediol.

[0033] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials with the following mass percentages:

[0034] Phase A:

[0035] First oil 5% - 20%,

[0036] Lecithin 1% - 2%,

[0037] Antioxidant 0.01% - 0.1%;

[0038] Phase B:

[0039] Nonionic surfactant 2% - 7%,

[0040] Polyol 2% - 7%,

[0041] Water 63.9% - 89.91%;

[0042] Phase C:

[0043] p-Hydroxyacetophenone 0.03% - 0.06% and

[0044] Pentanediol 0.05% - 2%.

[0045] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials with the following mass percentages:

[0046] Phase A:

[0047] First oil 10% - 20%,

[0048] Lecithin 1% - 2%,

[0049] Antioxidant: 0.01% - 0.05%;

[0050] Phase B:

[0051] Non - ionic surfactant: 2% - 5%,

[0052] Polyol: 4% - 7%,

[0053] Water: 65.95% - 89.99%;

[0054] Phase C:

[0055] p - Hydroxyacetophenone: 0.03% - 0.06% and

[0056] Pentanediol: 0.05% - 2%.

[0057] In one embodiment, the particle size of the pre - nanoemulsion capable of encapsulating oil - soluble active substances is 70 nm - 200 nm, and the PDI is 0.1 - 0.3.

[0058] The present invention also provides a preparation method of the pre - nanoemulsion capable of encapsulating oil - soluble active substances as described above, comprising the following steps:

[0059] Mix the first oil, lecithin and antioxidant to prepare a mixed solution of Phase A;

[0060] Mix the non - ionic surfactant, polyol and water to prepare a mixed solution of Phase B;

[0061] Mix the mixed solution of Phase A and the mixed solution of Phase B, and prepare a primary emulsion by the first normal - pressure homogenization treatment;

[0062] Perform the first high - pressure homogenization treatment on the primary emulsion.

[0063] In one embodiment, the preparation method of the pre - nanoemulsion capable of encapsulating oil - soluble active substances comprises the following steps:

[0064] Under the condition of 55°C - 85°C, dissolve the lecithin in the first oil, and after the solution becomes clear and transparent, add the antioxidant to prepare the mixed solution of Phase A;

[0065] Under the condition of 80°C - 85°C, mix the non - ionic surfactant, the polyol and the water to prepare the mixed solution of Phase B;

[0066] Add the mixed solution of Phase B to the mixed solution of Phase A, and prepare a primary emulsion by the first normal - pressure homogenization treatment;

[0067] After the primary emulsion is cooled to room temperature, perform the first high - pressure homogenization treatment on the primary emulsion to prepare the pre - nanoemulsion.

[0068] In one embodiment, the rate of the first atmospheric pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 4 min to 7 min.

[0069] In one embodiment, the pressure of the first high-pressure homogenization treatment is 300 bar to 900 bar, the rate is 4000 rpm to 8000 rpm, the time is 5 min to 15 min, and the number of times is 3 to 9 times.

[0070] In one embodiment, the method for preparing the pre-nanoemulsion capable of encapsulating the oil-soluble active substance further includes the steps of preparing a C-phase mixture and mixing the C-phase mixture with the pre-nanoemulsion.

[0071] The present invention also provides a nanoemulsion encapsulating an oil-soluble active substance, which includes a second oil, an oil-soluble active substance, and the pre-nanoemulsion capable of encapsulating the oil-soluble active substance as described above.

[0072] In one embodiment, by mass percentage, the nanoemulsion encapsulating the oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0073] Second oil 5% to 20%;

[0074] Oil-soluble active substance 0.05% to 1.5%; and

[0075] Pre-nanoemulsion capable of encapsulating the oil-soluble active substance 79.9% to 94.95%.

[0076] In one embodiment, the second oil is one or more of triglyceride caprylate / caprate, evening primrose oil, octyldodecanol, and isopropyl myristate.

[0077] In one embodiment, the oil-soluble active substance is selected from one or more of ceramide, salicylic acid, bisabolol, retinol and its derivatives, astaxanthin, 377, and glabridin.

[0078] The present invention also provides a method for preparing the nanoemulsion encapsulating the oil-soluble active substance as described in the above claims, which includes the following steps:

[0079] Mix the second oil, the oil-soluble active substance, and the pre-nanoemulsion capable of encapsulating the oil-soluble active substance as described above, and perform a second atmospheric pressure homogenization treatment and a second high-pressure homogenization treatment.

[0080] In one embodiment, the rate of the second atmospheric pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 4 min to 7 min.

[0081] In one embodiment, the second high-pressure homogenization treatment is performed at a pressure of 300 bar to 900 bar, at a speed of 4000 rpm to 8000 rpm, for a time of 5 min to 15 min, and for 3 to 9 times.

[0082] The present invention also provides a cosmetic, comprising the pre-nanoemulsion for encapsulating oil-soluble functional substances as described above, or the nanooemulsion encapsulating oil-soluble functional substances as described above.

[0083] In one embodiment, the cosmetic is selected from one or more of a facial mask, a skin lotion, an essence, a spray and an emulsion.

[0084] The present invention has at least the following beneficial effects:

[0085] The pre-nanoemulsion for encapsulating oil-soluble functional substances mainly comprises oil, lecithin, antioxidant, non-ionic surfactant of a specific type, polyol and water in a specific ratio. The pre-nanoemulsion with good stability under extreme environmental conditions such as freezing and high temperature is obtained through the coordination of the non-ionic surfactant and the polyol, and the particle size does not change significantly within 3 months. The pre-nanoemulsion has the advantages of good transdermal property, high encapsulation rate, small particle size, high bioavailability and good sustained-release performance. The pre-nanoemulsion can encapsulate a variety of oil-soluble functional substances, and can further obtain a nanoemulsion encapsulating oil-soluble functional raw materials with good stability, good transdermal property, high encapsulation rate, small particle size, high bioavailability and good sustained-release performance. The pre-nanoemulsion for encapsulating oil-soluble functional substances and the nanoemulsion encapsulating oil-soluble functional raw materials can both be applied to cosmetics.

[0086] The present invention simplifies the production process of nanoemulsions that can encapsulate oil-soluble functional substances under the premise of ensuring encapsulation rate and stability, such as optimizing to prepare a pre-nanoemulsion with good penetration-promoting effect and sustained release effect through high-pressure homogenization technology, effectively promoting percutaneous absorption of oil-soluble functional ingredients, and long-acting sustained release. Subsequently, only the pre-nanoemulsion needs to be mixed with oil and oil and oil-soluble functional substances to prepare a nanoemulsion with universal oil-soluble functional substances, which greatly reduces the difficulty, requirements and cost of preparing and producing nanoemulsions that encapsulate oil-soluble functional substances. The whole process has a high degree of mechanization, so that the product quality and process have good reproducibility and stability, and are easy to industrialize. In addition, the present invention reduces the exploration and exploration of functional substance encapsulation schemes through pre-nanoemulsion (pre-carrier) technology, reduces time and cost, simplifies the method steps of material encapsulation, and effectively promotes the application and development of carrier technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 TEM electron microscope image of the pre-nanoemulsion sample prepared in Example 5;

[0088] Figure 2The reference backscattered light spectrum of the pre-nanoemulsion sample prepared in Example 5;

[0089] Figure 3 The kinetic instability results of the pre-nanoemulsion sample prepared in Example 5;

[0090] Figure 4 The reference backscattered light spectrum of the essence containing pre-nanoemulsion prepared in Example 7;

[0091] Figure 5 The kinetic instability results of the essence containing pre-nanoemulsion prepared in Example 7.

[0092] Figure 6 The reference backscattered light spectrum of the essence containing glabridin pre-nanoemulsion prepared in Example 8;

[0093] Figure 7 The kinetic instability results of the essence containing glabridin pre-nanoemulsion prepared in Example 8. Detailed implementation manners

[0094] The present invention will be further described in detail below with reference to specific embodiments. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the disclosure of the present invention more thorough and comprehensive.

[0095] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0096] The terms "preferably", "more preferably", "more preferably", "even more preferably", etc. in the present invention refer to embodiments of the present invention that can provide certain beneficial effects in certain cases. However, in the same or other cases, other embodiments may also be preferred. In addition, the description of one or more preferred embodiments does not imply that other embodiments are not available, nor is it intended to exclude other embodiments from the scope of the present invention. That is, in the present invention, "preferably", "more preferably", "more preferably", "even more preferably", etc. are only used to describe embodiments or examples with better effects, but do not constitute a limitation on the protection scope of the present invention.

[0097] In the present invention, "further", "even further", "especially", etc. are used for descriptive purposes to indicate differences in content, but should not be construed as a limitation on the protection scope of the present invention.

[0098] In the present invention, "above" and "below" both include the recited number. For example, "below 1" means ≥1.

[0099] In the present invention, the meaning of "at least one" is more than one, such as one, two or more. The meaning of "multiple" or "several" is at least two, for example, two, three, etc. The meaning of "multiple layers" is at least two layers, for example, two layers, three layers, etc., unless otherwise specifically defined. In the description of the present invention, the meaning of "several" is at least one, for example, one, two, etc., unless otherwise specifically defined.

[0100] When a numerical range is disclosed in the present invention, the above range is considered continuous and includes the minimum value and the maximum value of the range, as well as each value between such minimum and maximum values. Further, when the range refers to integers, it includes each integer between the minimum and maximum values of the range. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0101] If there is no special instruction, all steps of the present invention can be carried out in sequence or randomly. For example, the method includes steps (a) and (b), which means that the method can include steps (a) and (b) carried out in sequence, or can also include steps (b) and (a) carried out in sequence. For example, it is mentioned that the method may further include step (c), which means that step (c) can be added to the method in any order. For example, the method can include steps (a), (b) and (c) in sequence, or can also include steps (a), (c) and (b), or can also include steps (c), (a) and (b), etc.

[0102] In the present invention, the terms "first" and "second" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" can explicitly or implicitly include at least one such feature.

[0103] In the present invention, "comprises", "includes", "contains", "has" or other variants are intended to cover non-closed inclusion, and there is no distinction between these terms. The term "contains" means that other steps and components can be added without affecting the final result. The compositions and methods / processes of the present invention contain, consist of, and consist essentially of the essential elements and limitations described herein, as well as any additional or optional components, ingredients, steps or limitations described herein.

[0104] In the present invention, there is no distinction between the terms "efficacy", "performance", "effect", and "function".

[0105] In the description of the embodiments of the present invention, the weights of the relevant components mentioned not only can refer to the specific contents of each component, but also can represent the proportional relationship of the weights between each component. Therefore, as long as the contents of the relevant components in the description of the embodiments of the present invention are enlarged or reduced in proportion, they are within the scope disclosed in the description of the embodiments of the present invention. Specifically, the weights described in the description of the embodiments of the present invention can be mass units well-known in the chemical industry such as μg, mg, g, kg, etc.

[0106] In the present invention, for the temperature parameter, unless otherwise specifically defined, it is allowed to be a constant temperature treatment, and it is also allowed to be treated within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. The room temperature referred to in the present invention means 0 to 40 °C, preferably 10 °C to 35 °C, and more preferably 20 °C to 30 °C. The normal pressure referred to in the present invention means about 1 atm, one atmospheric pressure.

[0107] Unless otherwise mentioned, the terms in the singular form can include the plural form and should not be understood as having a quantity of one.

[0108] In addition, the drawings of the present invention are not drawn at a scale of 1:1, and the relative sizes of each component are only drawn by way of example in the drawings for the convenience of understanding the present invention, but are not necessarily drawn according to the actual scale. The scale in the drawings does not constitute a limitation to the present invention.

[0109] As a new type of transdermal delivery system, nanoemulsions have been applied to encapsulate lipophilic active substances. Although nanoemulsions show excellent kinetic stability, they do not belong to thermodynamically stable systems. Like coarse emulsions, they have a tendency to spontaneously reduce the interfacial area between the dispersed phase and the dispersion medium, and will be affected by coalescence and Ostwald ripening, etc., which affect the stability of nanoemulsions and lead to the instability of nanoemulsions. How to design and simply prepare charge nanoemulsions with high stability and high encapsulation efficiency is the challenge faced by the current nanoemulsion technology. The traditional production method of nanoemulsions needs to conduct single-factor or orthogonal experiments on the formula and production parameters of nanoemulsions according to the characteristics of the encapsulated active substances themselves to determine the final preparation method. This process often requires staff with R & D experience and a long R & D cycle, which is often difficult for some small raw material preparation companies to achieve. Moreover, for the numerous oil-soluble active substances on the market, continuously changing the production methods and parameters in production also increases the production cost.

[0110] Therefore, the present invention provides a pre-nanoemulsion with good stability that can be used to encapsulate oil-soluble active substances. On the premise of ensuring the encapsulation efficiency and stability, the nanoemulsion production process of oil-soluble active substances is optimized to only require one step to prepare, greatly reducing the difficulty, requirements and cost of preparation and production, and increasing the repeatability and stability of production.

[0111] The technical solution is as follows:

[0112] A pre-nanoemulsion that can be used to encapsulate oil-soluble active substances, calculated as a percentage of the total mass of the pre-nanoemulsion (counted as 100% by mass), is mainly made from raw materials with the following mass percentages:

[0113] Phase A (oil phase):

[0114] The first oil 5% - 20%,

[0115] Lecithin 1% - 2%,

[0116] Antioxidant 0.01% - 0.1%;

[0117] Phase B (aqueous phase):

[0118] Non-ionic surfactant 2% - 7%,

[0119] Polyol 2% - 7%,

[0120] Water 63.9% - 89.99%;

[0121] The non-ionic surfactant is one or more of Tween-80, Stearyl alcohol polyether-21, Glycerol polyether-26, Behenyl alcohol polyether-25, and Polyglycerol-10 myristate.

[0122] It can be understood that, calculated as a percentage of the mass of the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances, the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances contains 5% - 20% of the first oil, including but not limited to 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. Preferably, calculated as a percentage of the mass of the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances, the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances contains 10% - 20% of the first oil.

[0123] In one embodiment, the first oil is one or more of glyceryl trioctanoate (GTCC), evening primrose oil, octyldodecanol, and isopropyl myristate. Optionally, the oil is one or more of octyldodecanol and glyceryl trioctanoate.

[0124] It can be understood that, calculated as a percentage of the mass of the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances, the pre-nanoemulsion that can be used to encapsulate oil-soluble active substances contains 1% - 2% of lecithin, including but not limited to 1%, 1.5%, or 2%.

[0125] As a natural ingredient emulsifier, lecithin has good biocompatibility, can fuse with the lipids of the skin stratum corneum, disrupt its bilayer arrangement structure, and promote the transdermal absorption of drugs. In the present invention, lecithin is compounded with a nonionic surfactant. By selecting the type of nonionic surfactant and adjusting the ratio, the strength and viscoelasticity of the interfacial film are improved, the fluidity of the interfacial film is reduced, the outward diffusion of the nonionic surfactant from the interface is blocked, and at the same time, through steric hindrance and electrostatic repulsion, the collision between droplets is hindered, and the physical stability of the nanoemulsion is improved.

[0126] In one embodiment, the lecithin is PC50 soybean lecithin.

[0127] It can be understood that, calculated by mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.01% - 0.1% antioxidant, including but not limited to 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.075%, 0.08%, 0.09% or 0.1%. Preferably, calculated by mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.01% - 0.05% antioxidant.

[0128] In one embodiment, the antioxidant is pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate).

[0129] It can be understood that, calculated by mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 2% - 7% nonionic surfactant, including but not limited to 2%, 3%, 4%, 5%, 6% or 7%. Preferably, calculated by mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 2% - 5% nonionic surfactant.

[0130] In the present invention, one or more nonionic surfactants among Tween-80, steareth-21, glyceryl polyether-26, beheneth-25 and polyglyceryl-10 myristate can enhance the skin penetration ability and the ability to fluidize the stratum corneum lipids, thereby enhancing the absorption of active ingredients.

[0131] Understandably, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 2% to 7% of polyol, including but not limited to 2%, 3%, 4%, 5%, 6% or 7%. Preferably, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 4% to 7% of polyol.

[0132] In the present invention, polyol and non-ionic surfactant have a synergistic effect, which can further reduce the interfacial tension of the pre-nanoemulsion, effectively reduce the Ostwald ripening rate of the system. At the same time, polyol as a cryoprotectant can reduce the crystallization temperature of the aqueous phase, thereby preparing a nanoemulsion with good stability under high temperature and freezing conditions.

[0133] In one embodiment, the polyol is a polyol having three or five carbon atoms. Further, the polyol is one or more of glycerol and pentanediol.

[0134] Understandably, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 63.9% to 89.99% of water, including but not limited to 63.9%, 65%, 65.95%, 66%, 67%, 68%, 69%, 70%, 72%, 75%, 77%, 80%, 82% or 89.99%. Preferably, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 65.95% to 89.99% of water.

[0135] In one embodiment, the preparation raw materials of the pre-nanoemulsion available for encapsulating oil-soluble active substances further contain a preservative.

[0136] In one embodiment, the preservative is a mixture of p-hydroxyacetophenone and pentanediol.

[0137] In one embodiment, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.03% to 0.06% of p-hydroxyacetophenone, including but not limited to 0.03%, 0.04%, 0.05% or 0.06%. Preferably, based on the mass percentage of the pre-nanoemulsion available for encapsulating oil-soluble active substances, the pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.04% to 0.05% of p-hydroxyacetophenone.

[0138] In one embodiment, based on the mass percentage of the pre-nanoemulsion available for encapsulating the oil-soluble active substance, the pre-nanoemulsion available for encapsulating the oil-soluble active substance contains 0.05% to 2% of pentylene glycol, including but not limited to 0.05%, 0.06%, 0.07%, 0.075%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.2%, 1.5%, 1.8% or 2%. Preferably, based on the mass percentage of the pre-nanoemulsion available for encapsulating the oil-soluble active substance, the pre-nanoemulsion available for encapsulating the oil-soluble active substance contains 0.5% to 1.5% of pentylene glycol.

[0139] In one embodiment, the pre-nanoemulsion available for encapsulating the oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0140] Phase A:

[0141] The first oil and fat 10% - 20%,

[0142] Lecithin 1% - 2%,

[0143] Antioxidant 0.01% - 0.05%;

[0144] Phase B:

[0145] Non-ionic surfactant 2% - 5%,

[0146] Polyol 4% - 7%,

[0147] Water 65.95% - 89.99%.

[0148] In one embodiment, the pre-nanoemulsion available for encapsulating the oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0149] Phase A:

[0150] The first oil and fat 5% - 20%,

[0151] Lecithin 1% - 2%,

[0152] Antioxidant 0.01% - 0.1%;

[0153] Phase B:

[0154] Non-ionic surfactant 2% - 7%,

[0155] Polyol 2% - 7%,

[0156] Water 63.9% - 89.91%;

[0157] Phase C:

[0158] p-Hydroxyacetophenone 0.03% - 0.06% and

[0159] Pentylene glycol 0.05% - 2%.

[0160] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials with the following mass percentages:

[0161] Phase A:

[0162] The first oil 10% - 20%,

[0163] Lecithin 1% - 2%,

[0164] Antioxidant 0.01% - 0.05%;

[0165] Phase B:

[0166] Non-ionic surfactant 2% - 5%,

[0167] Polyol 4% - 7%,

[0168] Water 65.95% - 89.99%;

[0169] Phase C:

[0170] p-Hydroxyacetophenone 0.03% - 0.06% and

[0171] Pentylene glycol 0.05% - 2%.

[0172] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials with the following mass percentages:

[0173] Phase A:

[0174] The first oil 5% - 20%,

[0175] Lecithin 1% - 2%,

[0176] Antioxidant 0.01% - 0.1%;

[0177] Phase B:

[0178] Non-ionic surfactant 2% - 7%,

[0179] Polyol 2% - 7%,

[0180] Deionized water the balance;

[0181] Phase C:

[0182] p-Hydroxyacetophenone 0.05%,

[0183] 1% of pentylene glycol.

[0184] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials in the following mass percentages:

[0185] Phase A:

[0186] 10% - 20% of the first oil

[0187] 1% - 2% of lecithin

[0188] 0.01% - 0.05% of antioxidant

[0189] Phase B:

[0190] 2% - 5% of non-ionic surfactant

[0191] 4% - 7% of polyol

[0192] The balance is deionized water.

[0193] Phase C:

[0194] 0.05% of p-hydroxyacetophenone

[0195] 1% of pentylene glycol.

[0196] In one embodiment, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials in the following mass percentages:

[0197] Phase A:

[0198] 20% of the first oil

[0199] 1% of lecithin, and

[0200] 0.03% of antioxidant

[0201] Phase B:

[0202] 4% of non-ionic surfactant

[0203] 7% of polyol

[0204] The balance is deionized water.

[0205] Phase C:

[0206] 0.05% of p-hydroxyacetophenone

[0207] 1% of pentylene glycol.

[0208] In the present invention, the pre-nanoemulsion capable of encapsulating oil-soluble active substances is a pale yellow milky liquid with a faint blue opalescence. After testing, the particle size of the pre-nanoemulsion capable of encapsulating oil-soluble active substances in the present invention is 70 nm to 200 nm, the PDI is 0.1 to 0.3, and the particle size does not change significantly after being placed at -15 °C and 45 °C for 3 months. Further, the particle size of the pre-nanoemulsion is 70 to 130 nm, and the PDI is 0.1 to 0.3.

[0209] After testing, the encapsulation efficiency of the pre-nanoemulsion provided by the embodiment of the present invention for oil-soluble active substances is more than 70%, and the encapsulation efficiency of the pre-nanoemulsion prepared in some embodiments for oil-soluble active substances is 90% ± 8%.

[0210] The above-mentioned pre-nanoemulsion capable of encapsulating oil-soluble active substances can encapsulate a variety of oil-soluble active substances, and has a high encapsulation efficiency, good stability, and good sustained-release performance. It can continuously release active ingredients or substances for a long time. When used in cosmetics, it can better exert the skin care effect.

[0211] The present invention also provides a preparation method of the pre-nanoemulsion capable of encapsulating oil-soluble active substances as described above, including the following steps:

[0212] Mix the first oil, lecithin and antioxidant to prepare a phase A mixture;

[0213] Mix the non-ionic surfactant, polyol and water to prepare a phase B mixture;

[0214] Mix the phase A mixture and the phase B mixture, and prepare a primary emulsion by the first atmospheric pressure homogenization treatment;

[0215] Perform the first high-pressure homogenization treatment on the primary emulsion.

[0216] In one embodiment, the preparation method of the pre-nanoemulsion capable of encapsulating oil-soluble active substances includes the following steps:

[0217] Under the condition of 55 °C to 85 °C, dissolve the lecithin in the first oil, and add the antioxidant after the solution becomes clear and transparent to prepare the phase A mixture;

[0218] Under the condition of 80 °C to 85 °C, mix the non-ionic surfactant, the polyol and the water to prepare the phase B mixture;

[0219] Add the phase B mixture to the phase A mixture, and prepare a primary emulsion by the first atmospheric pressure homogenization treatment;

[0220] After the primary emulsion is cooled to room temperature, perform the first high-pressure homogenization treatment on the primary emulsion to prepare the pre-nanoemulsion.

[0221] In one embodiment, the rate of the first atmospheric pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 4 min to 7 min.

[0222] In one embodiment, the pressure of the first high-pressure homogenization treatment is 300 bar to 900 bar, the rate is 4000 rpm to 8000 rpm, the time is 5 min to 15 min, and the number of times is 3 to 9 times.

[0223] In one embodiment, the method for preparing the pre-nanoemulsion capable of encapsulating oil-soluble active substances further includes the steps of preparing a C-phase mixture and mixing the C-phase mixture with the pre-nanoemulsion.

[0224] In one embodiment, the method for preparing the pre-nanoemulsion capable of encapsulating oil-soluble active substances includes the following steps a to d:

[0225] Step a, dissolving the lecithin in the oil, and then adding the antioxidant to dissolve to prepare a phase A;

[0226] Specifically, at a temperature of 55 °C to 85 °C, dissolve the lecithin in the oil, and after the solution is clear and transparent, add other components of phase A: fat-soluble active ingredients and antioxidants to prepare a phase A solution;

[0227] Specifically, the selectable temperature range can be 55 °C to 65 °C, 65 °C to 75 °C or 75 °C to 85 °C, and the specifically selectable temperatures can be 55 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C or 85 °C;

[0228] Step b, mixing and dissolving the non-ionic surfactant, polyol and deionized water to prepare phase B;

[0229] Further, mix and stir to dissolve at a temperature of 80 °C to 85 °C until the solution is clear and transparent.

[0230] Step c, homogenize phase B, and slowly pour phase A into phase B, and then homogenize again to prepare a primary emulsion. Further, the homogenization rate is 4000 rpm to 8000 rpm.

[0231] Step d, after the primary emulsion is cooled, it is subjected to high-pressure homogenization treatment to prepare a pre-nanoemulsion. Further, after the primary emulsion is cooled to room temperature, it is subjected to high-pressure homogenization treatment. Further, the pressure of high-pressure homogenization is 300 bar to 900 bar, and the number of times of high-pressure homogenization is 3 to 9 times (total number of times).

[0232] In the present invention, the high-pressure homogenization treatment makes the pre-nanoemulsion system have a smaller particle size, and is more uniform and stable.

[0233] In a specific example, the preparation method further includes step e of uniformly dispersing p-hydroxyacetophenone and pentanediol in the pre-nanoemulsion prepared in step d.

[0234] Specifically, p-hydroxyacetophenone and pentanediol can be first mixed to prepare a C-phase solution, and the C-phase solution is added to the pre-nanoemulsion prepared in step d and dispersed uniformly.

[0235] The present invention also provides a nanoemulsion encapsulating an oil-soluble active substance, which includes a second oil, an oil-soluble active substance, and the pre-nanoemulsion as described above that can be used to encapsulate the oil-soluble active substance.

[0236] In one embodiment, by mass percentage, the nanoemulsion encapsulating an oil-soluble active substance is mainly made of raw materials in the following mass percentages:

[0237] Second oil 5% - 20%;

[0238] Oil-soluble active substance 0.05% - 1.5%; and

[0239] Pre-nanoemulsion that can be used to encapsulate the oil-soluble active substance 79.9% - 94.95%.

[0240] In one embodiment, by mass percentage, the nanoemulsion encapsulating an oil-soluble active substance is mainly made of raw materials in the following mass percentages:

[0241] Second oil 5% - 20%;

[0242] Oil-soluble active substance 0.5% - 1.5%; and

[0243] Pre-nanoemulsion that can be used to encapsulate the oil-soluble active substance 79.9% - 94.5%.

[0244] In one embodiment, the second oil is one or more of glyceryl trioctanoate (GTCC), evening primrose oil, octyldodecanol, and isopropyl myristate.

[0245] In one embodiment, the oil-soluble active substance is selected from one or more of ceramide, salicylic acid, bisabolol, retinol and its derivatives, astaxanthin, 377, and glabridin.

[0246] The present invention also provides a preparation method of the nanoemulsion encapsulating an oil-soluble active substance as described in the above claims, including the following steps:

[0247] Mix the second oil, the oil-soluble active substance, and the pre-nanoemulsion as described above that can be used to encapsulate the oil-soluble active substance, and perform a second normal pressure homogenization treatment and a second high pressure homogenization treatment.

[0248] In one embodiment, the rate of the second atmospheric pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 4 min to 7 min.

[0249] In one embodiment, the pressure of the second high-pressure homogenization treatment is 300 bar to 900 bar, the rate is 4000 rpm to 8000 rpm, the time is 5 min to 15 min, and the number of times is 3 to 9 times.

[0250] The present invention also provides a cosmetic, comprising the pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above, or the nanoemulsion encapsulating an oil-soluble active substance as described above.

[0251] In one embodiment, the cosmetic is selected from one or more of a facial mask, skin lotion, essence, spray and lotion.

[0252] In one embodiment, the cosmetic is an essence, and the essence comprises the pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above.

[0253] In one embodiment, the mass percentage of the pre-nanoemulsion capable of encapsulating an oil-soluble active substance in the essence is 20% to 60%, including but not limited to 20%, 30%, 40%, 50% or 60%. Preferably, the mass percentage of the pre-nanoemulsion capable of encapsulating an oil-soluble active substance in the essence is 30% to 50%.

[0254] In one embodiment, the essence further comprises one or more of a humectant, an ion chelating agent, a thickening agent, a preservative and an emollient.

[0255] In one embodiment, by mass percentage, the essence comprises the following components: 20% to 60% of the pre-nanoemulsion capable of encapsulating an oil-soluble active substance, 3% to 5% of glycerol, 3% to 5% of butanediol, 0.5% to 2% of pentanediol, 0.02% to 0.05% of EDTA-2Na, 0.3% to 0.6% of AVC (acryloyldimethyltaurine ammonium / VP copolymer), 0.5% to 2% of polyglyceryl-10 myristate, 0.1% to 0.3% of p-hydroxyacetophenone, and the balance is deionized water.

[0256] The present invention also provides a preparation method of the above-mentioned essence, comprising the following steps:

[0257] After dispersing AVC in 30% - 50% water, add glycerin, butanediol, pentanediol, p - hydroxyacetophenone, EDTA - 2Na, polyglyceryl - 10 myristate, heat up to 80°C - 85°C, and keep warm (for example, keep warm for 25 min - 35 min); cool down (for example, cool down to room temperature), then add the above - mentioned pre - nanoemulsion that can be used to encapsulate oil - soluble active substances and mix evenly. After cooling to room temperature, make up water to 100%.

[0258] In one embodiment, the cosmetic is a serum, and the serum comprises the nanoemulsion encapsulating the oil - soluble active substance as described above.

[0259] In one embodiment, the mass percentage of the nanoemulsion encapsulating the oil - soluble active substance in the serum is 20% - 60%, including but not limited to 20%, 30%, 40%, 50% or 60%. Preferably, the mass percentage of the nanoemulsion encapsulating the oil - soluble active substance in the serum is 30% - 50%.

[0260] In one embodiment, the serum further comprises one or more of a humectant, an ion chelator, a thickener, a preservative and an emollient.

[0261] In one embodiment, by mass percentage, the serum comprises the following components: 20% - 60% of the nanoemulsion encapsulating the oil - soluble active substance, 3% - 5% of glycerin, 3% - 5% of butanediol, 0.5% - 2% of pentanediol, 0.02% - 0.05% of EDTA - 2Na, 0.3% - 0.6% of AVC (ammonium acryloyldimethyltaurate / VP copolymer), 0.5% - 2% of polyglyceryl - 10 myristate, 0.1% - 0.3% of p - hydroxyacetophenone, and the balance is deionized water.

[0262] The present invention also provides a preparation method of the above - mentioned serum, comprising the following steps:

[0263] After dispersing AVC in 30% - 50% water, add glycerin, butanediol, pentanediol, p - hydroxyacetophenone, EDTA - 2Na, polyglyceryl - 10 myristate, heat up to 80°C - 85°C, and keep warm (for example, keep warm for 25 min - 35 min); cool down (for example, cool down to room temperature), then add the above - mentioned nanoemulsion encapsulating the oil - soluble active substance and mix evenly. After cooling to room temperature, make up water to 100%.

[0264] The implementation solutions of the present application will be described in detail below in conjunction with embodiments. It should be understood that these embodiments are only used to illustrate the present application and not to limit the scope of the present application. For the experimental methods without specific conditions in the following embodiments, the guidance given in the present application is preferentially referred to, and it can also be carried out according to the experimental manuals or conventional conditions in the art, or according to the conditions recommended by the manufacturer, or referring to the experimental methods known in the art.

[0265] In the following specific embodiments, for the measurement parameters of raw material components, if there is no special instruction, there may be slight deviations within the weighing accuracy range. For the temperature and time parameters, acceptable deviations caused by instrument test accuracy or operation accuracy are allowed.

[0266] Example 1

[0267] This example provides four kinds of pre-nanoemulsions and their preparation methods, which are as follows:

[0268] Prepare Samples 1 to 4 according to the raw material ratio in Table 1. Mix the oil and lecithin (PC50 soy lecithin), and mechanically stir at 55°C to 85°C until completely dissolved; then add the antioxidant and stir until the solution is clear and transparent to obtain Phase A; mix the non-ionic surfactant, polyol and deionized water, and mechanically stir at 85°C until completely dissolved to obtain Phase B; dissolve 0.05% p-hydroxyacetophenone at room temperature in 1% pentanediol to obtain Phase C; first homogenize Phase B at 8000 rpm, and slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion drops to room temperature, perform high-pressure homogenization treatment, the rotation speed is 6000 rpm, the pressure is 700 bar, each time for 3 min, and a total of 5 times of high-pressure homogenization are performed to obtain the pre-nanoemulsion; after the pre-nanoemulsion drops to room temperature, add Phase C and disperse evenly.

[0269] Table 1

[0270]

[0271]

[0272] As can be seen from Table 1, when GTCC is used as the oil, the particle size and PDI of the prepared pre-nanoemulsion are the smallest, PDI < 0.3, indicating that the pre-nanoemulsion shows good monodispersion, the system is homogeneous and stable, and the Zeta potential < -30 mV, which more meets the stability requirements.

[0273] Example 2

[0274] This example provides two kinds of pre-nanoemulsions and their preparation methods, as well as two kinds of nanoemulsions loaded with oil-soluble functional substances and their preparation methods, which are as follows:

[0275] Prepare samples according to the raw material ratios in Table 2. Mix the oil and lecithin (PC50 soy lecithin), and mechanically stir at 55 °C to 85 °C until completely dissolved; then add the antioxidant and stir until the solution is clear and transparent to obtain Phase A; mix the non-ionic surfactant, polyol, and deionized water, and mechanically stir at 85 °C until completely dissolved to obtain Phase B; dissolve 0.05% p-hydroxyacetophenone in 1% pentanediol at room temperature to obtain Phase C; first homogenize Phase B at 8000 rpm, and slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion cools to room temperature, perform high-pressure homogenization treatment at a speed of 6000 rpm, a pressure of 700 bar, and each time for 3 min, and perform high-pressure homogenization 5 times in total to obtain the pre-nanoemulsion; after the pre-nanoemulsion cools to room temperature, add Phase C and disperse evenly.

[0276] Dissolve 1 g of the oil-soluble active substance in 10 g of GTCC. Respectively take 100 g of the above-mentioned pre-nanoemulsion, mix well and homogenize at 8000 rpm for 5 min, and then perform high-pressure homogenization treatment at a speed of 8000 rpm, a pressure of 700 bar, and each time for 3 min, and perform high-pressure homogenization 5 times in total to obtain the nanoemulsion encapsulating the oil-soluble active substance.

[0277] Table 2

[0278]

[0279] Since the oil-soluble active substance ceramide has poor solubility in the water system, appropriate oil and content are needed to provide sufficient oil-phase solubility to prevent the leakage of the oil-soluble active substance and cause the instability of the system. To increase the universality of the pre-nanoemulsion and improve the solubility and encapsulation effect for most oil-soluble substances, GTCC with a content of 20% is preferably used.

[0280] Example 3

[0281] This example provides five pre-nanoemulsions and their preparation methods, which are as follows:

[0282] Prepare Samples 1 to 5 according to the raw material ratios in Table 3. Mix lecithin (PC50) and GTCC, and mechanically stir at 85 °C until completely dissolved; then add the antioxidant and stir until the solution is clear and transparent to obtain Phase A; mix the non-ionic surfactant, polyol, and deionized water, and mechanically stir at 85 °C until completely dissolved to obtain Phase B; dissolve 0.05% p-hydroxyacetophenone in 1% pentanediol at room temperature to obtain Phase C; first homogenize Phase B at 8000 rpm, and slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion cools to room temperature, perform high-pressure homogenization treatment at a speed of 6000 rpm, a pressure of 700 bar, and each time for 3 min, and perform high-pressure homogenization 5 times in total to obtain the pre-nanoemulsion; after the pre-nanoemulsion cools to room temperature, add Phase C and disperse evenly. The results are shown in Table 3 below.

[0283] Table 3

[0284]

[0285] As can be seen from Table 3, by using the non-ionic surfactant described in the present invention, sufficient interfacial film strength can be provided to stabilize the nanoemulsion system. The prepared pre-nanoemulsion has good physical stability, with Zeta potential all < -30 mV and PDI all < 0.3. Among them, the pre-nanoemulsion prepared with Tween-80 as the non-ionic surfactant has the smallest particle size. Therefore, Tween-80 is preferably used as the non-ionic surfactant.

[0286] Example 4

[0287] This example provides four pre-nanoemulsions and their preparation methods, which are as follows:

[0288] The raw material formulas of the four pre-nanoemulsions are the same. The pre-nanoemulsion contains the following raw materials in mass percentages:

[0289]

[0290] At 80 °C to 85 °C under stirring, dissolve lecithin in caprylic / capric triglyceride, and then add pentaerythritol tetra(bis-tert-butyl hydroxyhydrocinnamate) to obtain Phase A; mix Tween-80, glycerol, 1% pentylene glycol and deionized water, heat to 80 °C to 85 °C, and stir until the solution is clear and transparent to obtain Phase B; dissolve p-hydroxyacetophenone in 1% pentylene glycol at room temperature to obtain Phase C; first homogenize Phase B at 8000 rpm, slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion is cooled to room temperature, perform high-pressure homogenization treatment at a speed of 6000 rpm, a pressure of 300 - 900 bar, each time for 3 min, and perform high-pressure homogenization 5 times in total to obtain the pre-nanoemulsion; after the pre-nanoemulsion is cooled to room temperature, add Phase C and disperse evenly. The test results are shown in Table 4 below.

[0291] Table 4

[0292] Item Sample 1 Sample 2 Sample 3 Sample 4 High-pressure homogenization pressure / bar 300 500 700 900 Particle size / nm 168.2 150.9 125.5 126.6 PDI 0.08759 0.1405 0.1491 0.1883 Zeta potential (mV) -39.22 -41.78 -40.8 -39.43

[0293] As can be seen from Table 4, by adjusting the high-pressure homogenization pressure during the preparation of the pre-nanoemulsion, as the pressure increases, the particle size and PDI of the prepared pre-nanoemulsion gradually decrease. The data at 700 bar and 900 bar are similar. To save time and cost, 700 bar is preferably used as the preparation condition.

[0294] Example 5

[0295] This example provides four pre-nanoemulsions and their preparation methods, which are as follows:

[0296] The raw material formulas of the four pre-nanoemulsions are the same. The pre-nanoemulsion contains the following raw materials in mass percentages:

[0297]

[0298]

[0299] At 80 °C to 85 °C, under stirring conditions, dissolve lecithin in caprylic / capric triglyceride, and then add pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate) to obtain Phase A; mix Tween-80, glycerol, 1% pentylene glycol and deionized water, heat to 80 °C to 85 °C, and stir until the solution is clear and transparent to obtain Phase B; dissolve p-hydroxyacetophenone in 1% pentylene glycol at room temperature to obtain Phase C; first homogenize Phase B at 8000 rpm, slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion is cooled to room temperature, perform high-pressure homogenization treatment at a rotation speed of 6000 rpm, a pressure of 700 bar, and a time of 3 min each time, and perform high-pressure homogenization 3 to 9 times in total to obtain the pre-nanoemulsion; after the pre-nanoemulsion is cooled to room temperature, add Phase C and disperse evenly. The results are shown in Table 5 below.

[0300] Table 5

[0301] Item Sample 1 Sample 2 Sample 3 Sample 4 Number of high-pressure homogenization times 3 5 7 9 Particle size / nm 143.4 125.5 118.1 110.7 PDI 0.1255 0.1491 0.1723 0.1685 Zeta potential (mV) -38.95 -40.8 -39.4 -42.97

[0302] As can be seen from Table 5, by adjusting the number of high-pressure homogenization times during the preparation of the pre-nanoemulsion, as the pressure increases, the particle size of the prepared pre-nanoemulsion gradually decreases, and the PDI < 0.3, but it is not stable enough and has an upward trend. Considering comprehensively that the increase in the number of high-pressure homogenization times also increases the process difficulty, 7 times is preferably the better preparation condition.

[0303] Example 6

[0304] This example provides a pre-nanoemulsion and its preparation method, as well as six nanoemulsions loaded with different oil-soluble active substances and their preparation methods, specifically as follows:

[0305] A pre-nanoemulsion containing the following raw materials in mass percentages:

[0306]

[0307]

[0308] At 55 °C to 60 °C, under stirring conditions, dissolve lecithin in caprylic / capric triglyceride, and then add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) to obtain Phase A; mix Tween-80, glycerol, 1% pentylene glycol and deionized water, heat to 80 °C to 85 °C, and stir until the solution is clear and transparent to obtain Phase B; dissolve p-hydroxyacetophenone in 1% pentylene glycol at room temperature to obtain Phase C; first homogenize Phase B at 8000 rpm, slowly pour it into Phase A, and homogenize for 5 min to obtain the primary emulsion; after the primary emulsion cools to room temperature, perform high-pressure homogenization treatment at a rotation speed of 6000 rpm, a pressure of 700 bar, and each time for 3 min, and perform high-pressure homogenization 7 times in total to obtain the pre-nanoemulsion; after the pre-nanoemulsion cools to room temperature, add Phase C and disperse evenly.

[0309] Dissolve 1 g of the oil-soluble active substance shown in Table 6 in 10 g of GTCC. Respectively take 100 g of the above-mentioned pre-nanoemulsion, mix well and homogenize at 8000 rpm for 5 min, and then perform high-pressure homogenization treatment at a rotation speed of 6000 rpm, a pressure of 700 bar, and each time for 3 min. Perform high-pressure homogenization 7 times in total to obtain the nanoemulsion encapsulating the oil-soluble active substance.

[0310] Perform an encapsulation efficiency test on the nanoemulsion encapsulating the oil-soluble active substance prepared in Example 6, specifically as follows:

[0311] Absorb a certain amount of the nanoemulsion sample, add 5 mL of methanol, mix well and ultrasonicate for 15 min, and then make up the volume to 10 mL. Take a certain amount of the demulsified sample and dilute it 5 times, measure the absorbance, and calculate the total content of the corresponding substance and record it as W1. Then filter 1 mL of the nanoemulsion through a 0.22 μm filter membrane 3 times, transfer 100 μL of the filtered sample, add 5 mL of methanol, mix well and ultrasonicate for 15 min, and then make up the volume to 10 mL. Take a certain amount of the demulsified sample and dilute it 5 times, measure the absorbance, and calculate the encapsulated content of the corresponding substance and record it as W2. The calculation formula is as follows:

[0312]

[0313] The results are shown in Table 6 below.

[0314] Table 6

[0315] Item Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Loaded active substance Salicylic acid Bisabolol HPR Astaxanthin 377 Glabridin Particle size / nm 125.3 132.1 130.1 133.3 127.1 131.2 PDI 0.08121 0.1035 0.1133 0.1166 0.1103 0.1052 Zeta potential (mV) -34.3 -46.46 -46.33 -45.6 -48.22 -47.83 Entrapment efficiency (%) 90.53 91.2 98.33 89.7 72.47 94.53

[0316] As can be seen from Table 6, the pre-nanoemulsion prepared in the examples of the present invention can be used to encapsulate oil-soluble active substances, and the encapsulation efficiency of the pre-nanoemulsion for various oil-soluble active substances is more than 70%, and some can reach more than 98%.

[0317] Example 7

[0318] This example provides an essence containing the pre-nanoemulsion prepared in Sample 3 of Example 4, and its component ratio is shown in Table 7.

[0319] Table 7

[0320]

[0321] The preparation method is as follows:

[0322] First, disperse AVC in 50% water, then add glycerol, butanediol, pentanediol, p-hydroxyacetophenone, EDTA-2Na, and polyglyceryl-10 myristate. After heating to 85°C, keep warm for 30 min; after cooling to room temperature, add the pre-nanoemulsion and mix evenly, and make up the water to 100%.

[0323] Example 8

[0324] This example provides an essence containing a nanoemulsion loaded with the oil-soluble active substance glabridin prepared from the sample 6 in Example 6, and its component ratio is shown in Table 8.

[0325] Table 8

[0326]

[0327]

[0328] The preparation method is as follows:

[0329] First, disperse AVC in 50% water, then add glycerol, butanediol, pentanediol, p-hydroxyacetophenone, EDTA-2Na, and polyglyceryl-10 myristate. After heating to 85°C, keep warm for 30 min; after cooling to room temperature, add 0.09% glabridin nanoemulsion prepared in Example 6 and mix evenly, and make up the water to 100%.

[0330] Comparative Example 1

[0331] Comparative Example 1 provides a pre-nanoemulsion and its preparation method, which is basically the same as sample 3 in Example 5, except that it is not subjected to high-pressure homogenization treatment.

[0332] The pre-nanoemulsion without high-pressure homogenization treatment is a milky yellow viscous liquid with a particle size of 660 nm. Compared with sample 3 in Example 5, the particle size increases by 530 nm. And its stability is poor. After the emulsion is placed for three days, it shows upper and lower stratification. The upper layer is milky white, and the lower layer is a light yellow turbid liquid.

[0333] Comparative Example 2

[0334] Comparative Example 2 provides a nanoemulsion, which is basically the same as Example 6, except that the prepared pre-nanoemulsion and the GTCC solution of the active substance are not homogenized under normal pressure and are directly subjected to high-pressure homogenization.

[0335] After testing, precipitation of the active substances occurred after the nanoemulsion was placed for three days under normal conditions.

[0336] Test Example 1 Investigation of the Stability of Nanoemulsion

[0337] Samples 3 of Example 5 and Sample 6 of Example 6 were respectively placed under normal conditions, light, dark, 4°C, 45°C, -15°C, and freeze-thaw cycle (one freeze-thaw cycle is to place at -15°C for 24 h and then at 45°C for 24 h), and their particle size stability was measured. The results are shown in Table 9.

[0338] Table 9

[0339]

[0340]

[0341] As can be seen from Table 9, for the pre-nanoemulsion Sample 3 prepared in Example 5 and Sample 6 of Example 6, the Zeta potential was <-30 mV, the PDI was <0.3, and the particle size was <200 nm within 90 days, and the fluctuation was small, indicating good physical stability.

[0342] Test Example 2 TEM Observation of the Morphology of Pre-Nanoemulsion

[0343] The pre-nanoemulsion Sample 3 prepared in Example 5 was subjected to TEM detection.

[0344] Weigh Sample 3 prepared in Example 5 and drop it on a copper grid. After a few seconds, gently pick up the copper grid sample with forceps, and absorb the excess liquid along one side with filter paper. After it is slightly dry, place the copper grid on a 2% phosphotungstic acid staining solution drop for floating staining for 60 s. After picking it up with forceps, also absorb the excess liquid along one side with filter paper, place it film-side up on the filter paper to dry, and observe and take pictures with a transmission electron microscope. The results are as Figure 1 shown. It can be seen that the nanoemulsion particles are spherical-like and the distribution is relatively uniform.

[0345] Test Example 3 Comparative Investigation of the Stability of Essence

[0346] Absorb a certain amount of Sample 3 of Example 5, Example 7, and Sample of Example 8 into the sample bottles of the Turbiscan Lab stability analyzer, and measure the dynamic changes in the stability of the essence. The parameter settings are to scan once every 30 min and the scanning time is 24 h. The experimental results of Sample 3 of Example 5 are shown in Figures 2 to 3 , in terms of the kinetic stability index (TSI) of the two, the smaller the TSI index, the better the stability. From this, it can be seen that the stability of the pre-nanoemulsion is good. The experimental results of Example 7 are shown in Figures 4 to 5, in terms of the kinetic stability index (TSI) of the two, the smaller the TSI index, the better the stability. From this, it can be seen that the essence containing pre-nanoemulsion has good stability, indicating that pre-nanoemulsion can be simply and stably applied to cosmetic formulations. For the experimental results of Example 8, see Figures 6 to 7 , in terms of the kinetic stability index (TSI) of the two, the smaller the TSI index, the better the stability. From this, it can be seen that the essence containing glabridin pre-nanoemulsion has good stability. Further, from Figure 2 、 Figure 3 it can be known that the reference spectrum tends to be a straight line, indicating that Sample 3 of Example 5 has good stability, ΔBS = 0, less than 0.2, and is in an absolutely stable state. From Figure 4 、 Figure 5 it can be known that the reference spectrum curve has a certain fluctuating trend and the TSI value is relatively large, indicating that Example 7 is not as stable as Sample 3 of Example 5, but ΔBS = 0.03, less than 0.2, and is also in an absolutely stable state. From Figure 6 、 Figure 7 it can be known that the reference spectrum tends to be a straight line, and ΔBS = 0.11, less than 0.2, and is in an absolutely stable state, indicating that Example 8 has good stability and can be stably applied to cosmetic formulations.

[0347] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0348] The above-described embodiments only represent several implementation manners of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. A pre-nanoemulsion that can be used to encapsulate oil-soluble active substances, characterized in that, It is mainly made of raw materials with the following mass percentages: Phase A: The first grease 5% - 20%, Lecithin 1% - 2%, Antioxidant 0.01% - 0.1%; Phase B: Non-ionic surfactant 2% - 7%, Polyol 2% - 7%, Water 63.9% - 89.99%; The non-ionic surfactant is one or more of Tween-80, Stearyl alcohol polyether-21, Glycerol polyether-26, Behenyl alcohol polyether-25, and Polyglycerol-10 myristate.

2. The pre-nanoemulsion according to claim 1, which can be used for encapsulating oil-soluble active substances, is characterized in that, It is mainly made of raw materials with the following mass percentages: Phase A: The first grease 10% - 20%, Lecithin 1% - 2%, Antioxidant 0.01% - 0.05%; Phase B: Non-ionic surfactant 2% - 5%, Polyol 4% - 7%, Water 65.95% - 89.99%.

3. The pre-nanoemulsion according to claim 1, which is capable of encapsulating an oil-soluble active substance, is characterized in that, Meet one or more of the following conditions (1) - (4): (1) The first grease is one or more of triglyceride caprylate / caprate, evening primrose oil, octyldodecanol, and isopropyl myristate; (2) The lecithin is PC50 soy lecithin; (3) The antioxidant is pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate); (4) The polyol is one or more of glycerol and pentanediol.

4. The pre-nanoemulsion for encapsulating oil-soluble active substances according to any one of claims 1 to 3, characterized in that, The raw materials also contain a preservative.

5. The pre-nanoemulsion according to claim 4, which can be used for encapsulating oil-soluble active substances, is characterized in that, The preservative is a mixture of p-hydroxyacetophenone and pentanediol. The mass percentage of p-hydroxyacetophenone in the pre-nanoemulsion is 0.03% - 0.06%, and the mass percentage of pentanediol in the pre-nanoemulsion is 0.05% - 2%.

6. The pre-nanoemulsion for encapsulating an oil-soluble active substance according to any one of claims 1 to 3, characterized in that, The particle size of the nanoemulsion is 70nm - 200nm, and the PDI is 0.1 - 0.

3.

7. A method for preparing a pre-nanoemulsion according to any one of claims 1 to 6, which can be used for encapsulating oil-soluble active substances, characterized in that, It includes the following steps: Mix the first grease, lecithin, and antioxidant to prepare a Phase A mixture; Mix the non-ionic surfactant, polyol, and water to prepare a Phase B mixture; Mix the Phase A mixture with the Phase B mixture and prepare a primary emulsion through atmospheric pressure homogenization; Perform high-pressure homogenization on the primary emulsion.

8. The preparation method of the pre-nanoemulsion capable of encapsulating oil-soluble active substances according to claim 7, characterized in that, It includes the following steps: Under the condition of 55°C - 85°C, dissolve the lecithin in the first grease, and add the antioxidant after the solution becomes clear and transparent to prepare the Phase A mixture; Under the condition of 80°C - 85°C, mix the non-ionic surfactant, the polyol, and the water to prepare the Phase B mixture; Add the Phase B mixture to the Phase A mixture and prepare a primary emulsion through the first atmospheric pressure homogenization; After the primary emulsion is cooled to room temperature, perform the first high-pressure homogenization on the primary emulsion to prepare a pre-nanoemulsion.

9. The preparation method of the pre-nanoemulsion capable of encapsulating oil-soluble active substances according to claim 7 or 8, characterized in that, Meet one or more of the following conditions (1) - (2): (1) The rate of the first atmospheric pressure homogenization is 4000rpm - 8000rpm, and the time is 4min - 7min; (2) The pressure of the first high-pressure homogenization is 300bar - 900bar, the rate is 4000rpm - 8000rpm, the time is 5min - 15min, and the number of times is 3 - 9 times.

10. The preparation method of the pre-nanoemulsion capable of encapsulating oil-soluble functional substances according to claim 7 or 8, characterized in that, It also includes the step of preparing a Phase C mixture and mixing the Phase C mixture with the pre-nanoemulsion.

11. A nanoemulsion encapsulating an oil-soluble active substance, characterized in that, It includes a second oil, an oil-soluble active ingredient, and the pre-nanoemulsion capable of encapsulating the oil-soluble active ingredient according to any one of claims 1 to 6.

12. The nanoemulsion encapsulating an oil-soluble active substance according to claim 11, wherein, By mass percentage, it is mainly made of raw materials with the following mass percentages: The second oil: 5% - 20%; The oil-soluble active ingredient: 0.05% - 1.5%; and The pre-nanoemulsion capable of encapsulating the oil-soluble active ingredient: 79.9% - 94.95%.

13. The nanoemulsion encapsulating an oil-soluble active substance according to claim 11 or 12, characterized in that, It meets one or more of the following conditions (1) - (2): (1) The second oil is one or more of triglyceride caprylate / caprate, evening primrose oil, octyldodecanol, and isopropyl myristate; (2) The oil-soluble active ingredient is selected from one or more of ceramide, salicylic acid, bisabolol, retinol and its derivatives, astaxanthin, 377, and glabridin.

14. A method for preparing the nanoemulsion encapsulating an oil-soluble active substance according to any one of claims 11 to 13, characterized in that, It includes the following steps: Mix the second oil, the oil-soluble active ingredient, and the pre-nanoemulsion capable of encapsulating the oil-soluble active ingredient according to any one of claims 1 to 6, and perform a second atmospheric pressure homogenization treatment and a second high-pressure homogenization treatment.

15. The preparation method of the nanoemulsion encapsulating an oil-soluble active substance according to claim 14, characterized in that, It meets one or more of the following conditions (1) - (2): (1) The rate of the second atmospheric pressure homogenization treatment is 4000 rpm - 8000 rpm, and the time is 4 min - 7 min; (2) The pressure of the second high-pressure homogenization treatment is 300 bar - 900 bar, the rate is 4000 rpm - 8000 rpm, the time is 5 min - 15 min, and the number of times is 3 - 9 times.

16. A cosmetic, characterized in that, It includes the pre-nanoemulsion capable of encapsulating the oil-soluble active ingredient according to any one of claims 1 to 6, or the nanoemulsion encapsulating the oil-soluble active ingredient according to any one of claims 11 to 13.

17. The cosmetic according to claim 16, characterized in that, The cosmetic is selected from one or more of facial masks, skin toners, essence liquids, sprays, and lotions.

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