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

Abstract

The invention relates to a cationic pre-nanoemulsion capable of being used for encapsulating an oil-soluble functional substance as well as a preparation method and application of the cationic pre-nanoemulsion. The cationic pre-nanoemulsion is mainly prepared from the following raw materials in percentage by mass: a phase A: 10%-20% of first grease, 1%-5% of lecithin, 0.3%-0.8% of a positive charge inducer phytosphingosine and 0.03%-0.2% of an antioxidant; a phase B: 2%-6% of a nonionic surfactant, 2%-6% of polyol and 62%-84.67% of water; the nonionic surfactant is one or more of cetearyl alcohol polyether-25, cetearyl alcohol polyether-20, beheneth-25 and stearyl alcohol polyether-21. The preparation method comprises the following steps: preparing the surfactant; the cationic pre-nano-emulsion can improve the stability of oil-soluble functional components, can wrap various oil-soluble functional substances, can further obtain a nano-emulsion wrapped with oil-soluble functional raw materials, and both the cationic pre-nano-emulsion and the nano-emulsion can be used in cosmetics.

Description

Technical Field

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

[0002] A 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. The droplet size is usually distributed in the range of 50-500 nm, and it is a transparent or semi-transparent emulsion system.

[0003] Compared with ordinary emulsions, nanoemulsions have smaller particle sizes, more stable kinetics, better dispersibility, and better long-term stability. There will be no significant flocculation, sedimentation, and coalescence phenomena for a long time, which can effectively ensure the shelf-life stability of cosmetics. Moreover, due to the small droplet size and large surface area of the nanoemulsion system, it is more conducive to the transmission and transdermal absorption of the inner-phase active ingredients. At the same time, in the nanoemulsion system, both efficacy and safety are emphasized, and the use of penetration enhancers and surfactants is reduced, which can eliminate the potential irritation to the skin.

[0004] In view of the above-mentioned many advantages of nanoemulsions, they have been widely used as efficacy transmission systems for cosmetics. However, traditional nanoemulsion technologies all encapsulate a single substance and cannot be applied to different oil-soluble components. In addition, the stability and percutaneous penetration promotion of traditional nanoemulsions still need to be improved. Summary of the Invention

[0005] Based on this, the purpose of the present invention is to provide a cationic 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. Both the cationic pre-nanoemulsion and the nanoemulsion can be applied to cosmetics.

[0006] The technical solution is as follows:

[0007] A cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made of raw materials with the following mass percentages:

[0008] Phase A:

[0009]

[0010] Phase B:

[0011] Non-ionic surfactant 2% - 6%,

[0012] Polyol 2% - 6%,

[0013] Water 62% - 84.67%;

[0014] The positive charge inducer is phytosphingosine;

[0015] The non-ionic surfactant is one or more of cetostearyl alcohol polyether-25, cetyl alcohol polyether-20, behenyl alcohol polyether-25, and stearyl alcohol polyether-21.

[0016] In one embodiment, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly made from raw materials in the following mass percentages:

[0017] Phase A:

[0018]

[0019] Phase B:

[0020] Non-ionic surfactant 2% - 5%,

[0021] Polyol 4% - 6%,

[0022] Water 65.1% - 78.47%.

[0023] In one embodiment, the first oil is one or more of triglyceride caprylate / caprate and octyldodecanol.

[0024] In one embodiment, the lecithin is PC50 soy lecithin.

[0025] In one embodiment, the antioxidant is pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate).

[0026] In one embodiment, the polyol is glycerol.

[0027] In one embodiment, the raw materials further include a preservative, and the mass percentage in the cationic pre-nanoemulsion is 0.05% - 0.15%.

[0028] In one embodiment, the preservative is potassium sorbate.

[0029] In one embodiment, the raw materials further include a pH regulator, and the mass percentage in the cationic pre-nanoemulsion is 0.5% - 2%.

[0030] In one embodiment, the pH regulator is citric acid.

[0031] In one embodiment, the particle size of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is 70nm - 200nm, the PDI is 0.05 - 0.25, and the pH is 4.5 - 7.0.

[0032] There is also provided a method for preparing a cationic pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above, comprising the following steps:

[0033] Mix a first oil, lecithin, a positive charge inducer, and an antioxidant to prepare a phase A mixture;

[0034] Mix a nonionic surfactant, a polyol, and water to prepare a phase B mixture;

[0035] Mix the phase A mixture with the phase B mixture and prepare a primary emulsion by first normal pressure homogenization;

[0036] Perform a first high-pressure homogenization treatment on the primary emulsion.

[0037] In one embodiment, the method for preparing a cationic pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above comprises the following steps:

[0038] Dissolve the positive charge inducer in the first oil at 100 °C to 110 °C. After the solution becomes clear and transparent, cool it to 40 °C to 60 °C, and add the lecithin and the antioxidant to prepare the phase A mixture;

[0039] Mix the nonionic surfactant, the polyol, and the water at 40 °C to 60 °C to prepare the phase B mixture;

[0040] Add the phase B mixture to the phase A mixture and prepare a primary emulsion by normal pressure homogenization;

[0041] After the primary emulsion is cooled to room temperature, perform a high-pressure homogenization treatment on the primary emulsion to prepare the cationic pre-nanoemulsion.

[0042] In one embodiment, the rate of the first normal pressure homogenization is 4000 rpm to 8000 rpm, and the time is 5 min to 15 min.

[0043] In one embodiment, the pressure of the first high-pressure homogenization 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.

[0044] In one embodiment, the method for preparing a cationic pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above comprises the step of mixing a preservative and / or a pH regulator with the cationic pre-nanoemulsion.

[0045] The present invention also provides a nanoemulsion encapsulating an oil-soluble active substance, comprising a second oil, an oil-soluble active substance, and a cationic pre-nanoemulsion capable of encapsulating an oil-soluble active substance as described above.

[0046] In one embodiment, the nanoemulsion encapsulating the oil-soluble active substance is mainly made of raw materials in the following mass percentages:

[0047] The second oil 5% - 20%;

[0048] The oil-soluble active substance 0.05% - 2%; and

[0049] The cationic pre-nanoemulsion capable of encapsulating the oil-soluble active substance 78% - 94.95%.

[0050] In one embodiment, the second oil is one or more of triglyceride caprylate / caprate and octyldodecanol.

[0051] In one embodiment, the oil-soluble active substance is selected from one or more of HPR, 377, and glabridin.

[0052] The present invention also provides a method for preparing the nanoemulsion encapsulating the oil-soluble active substance as described above, comprising the following steps:

[0053] Mix the second oil, the oil-soluble active substance, and the cationic pre-nanoemulsion capable of encapsulating the oil-soluble active substance as described above, and perform the second atmospheric pressure homogenization treatment and the second high-pressure homogenization treatment.

[0054] In one embodiment, the rate of the second atmospheric pressure homogenization treatment is 4000 rpm - 8000 rpm, and the time is 4 min - 7 min.

[0055] In one embodiment, the pressure of the second high-pressure homogenization treatment is 300 bar - 900 bar, the rate is 4000 rpm - 8000 rpm, the time is 3 min - 15 min, and the number of times is 3 - 9 times.

[0056] The present invention also provides a cosmetic, which comprises the cationic pre-nanoemulsion capable of encapsulating the oil-soluble active substance as described above, or the nanoemulsion encapsulating the oil-soluble active substance as described above.

[0057] In one embodiment, the cosmetic is selected from one or more of facial masks, skin toners, essence, sprays, and lotions.

[0058] The present invention has at least the following beneficial effects:

[0059] The cationic pre-nanoemulsion capable of encapsulating the oil-soluble active substance of the present invention mainly comprises oils and fats, lecithin, phytosphingosine, antioxidants, specific types of non-ionic surfactants, polyols, and water in specific ratios. Among them, phytosphingosine is pK bThe free sphingoid base of about 9, so the amino group in its structure is protonated at a physiological skin pH of 5.5, thereby providing a positive charge for the nanodroplets. Due to the presence of negatively charged protein amino acid residues and selectively active ion pumps on the cell outer membrane, all epithelial cell surfaces, including the skin, carry negative charges. Under physiological conditions, the electrostatic attraction between the cationic nanoemulsion and the skin can make the active substances encapsulated therein have better permeability, more easily diffuse into the skin, and improve the bioavailability of the effective ingredients. Through the coordination of non-ionic surfactants and polyols, a pre-nanoemulsion with good stability under extreme environmental conditions such as freezing and high temperature is obtained, and the particle size does not change significantly within 3 months.

[0060] The cationic pre-nanoemulsion provided by the present invention has good stability, can encapsulate one or more oil-soluble functional ingredients, and has the advantages of good transdermal properties, high encapsulation rate, small particle size, and high bioavailability, and the pre-nanoemulsion has good sustained-release performance, can play the role of a storage depot in the skin, can continuously release the functional ingredients for a long time, and better play the skin care effect. Through the cationic pre-nanoemulsion, a nanoemulsion containing oil-soluble functional raw materials with good stability, good transdermal properties, high encapsulation rate, small particle size, high bioavailability, and good sustained-release performance can be further obtained, and the cationic pre-nanoemulsion that can be used to encapsulate oil-soluble functional substances and the nanoemulsion containing oil-soluble functional raw materials can be applied to cosmetics.

[0061] In addition, 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 encapsulation of oil-soluble functional substances, which greatly reduces the difficulty, requirements and cost of preparing and producing nanoemulsions encapsulating 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

[0062] Figure 1 The particle size distribution diagram of the cationic pre-nanoemulsion prepared in Example 7;

[0063] Figure 2 is the backscattered light reference spectrum of the pre-nanoemulsion sample prepared in Example 7;

[0064] Figure 3Results of the kinetic instability of the pre-nanoemulsion sample prepared in Example 7;

[0065] Figure 4 Reference backscattered light spectrum of the pre-nanoemulsion sample prepared in Example 9;

[0066] Figure 5 Results of the kinetic instability of the pre-nanoemulsion sample prepared in Example 9;

[0067] Figure 6 Reference backscattered light spectrum of the pre-nanoemulsion sample prepared in Example 10;

[0068] Figure 7 Results of the kinetic instability of the pre-nanoemulsion sample prepared in Example 10;

[0069] Figure 8 TEM electron micrograph of the morphology of the cationic pre-nanoemulsion prepared in Example 7;

[0070] Figure 9 Results of the cumulative retention amount of the cationic pre-nanoemulsion loaded with glabridin prepared in Example 8 and the glabridin negative charge pre-nanoemulsion in Comparative Example 3 in the Franz diffusion cell transdermal experiment;

[0071] Figure 10 Results of the cumulative permeation amount of the cationic pre-nanoemulsion loaded with glabridin prepared in Example 8 and the glabridin negative charge pre-nanoemulsion in Comparative Example 3 in the Franz diffusion cell transdermal experiment. Detailed implementation mode

[0072] 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, the purpose of providing these embodiments is to make the understanding of the disclosed content of the present invention more thorough and comprehensive.

[0073] 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 specification 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.

[0074] The terms "preferably", "more preferably", "more desirably", "even more desirably", 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 desirably", "even more desirably", 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.

[0075] 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 limiting the protection scope of the present invention.

[0076] In the present invention, "above" and "below" both include the recited number. For example, "below 1" means ≥1.

[0077] 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, such as two, three, etc. The meaning of "multiple layers" is at least two layers, such as two layers, three layers, etc., unless otherwise specifically defined. In the description of the present invention, the meaning of "several" is at least one, such as one, two, etc., unless otherwise specifically defined.

[0078] When a numerical range is disclosed in the present invention, the above range is considered continuous and includes the minimum and maximum values of the range, as well as every value between such minimum and maximum values. Further, when the range refers to integers, it includes every 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.

[0079] If there is no special indication, all steps of the present invention can be carried out sequentially or randomly. For example, the method includes steps (a) and (b), which means that the method can include steps (a) and (b) carried out sequentially, or can also include steps (b) and (a) carried out sequentially. 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.

[0080] In the present invention, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one such feature.

[0081] In the present invention, "comprising", "including", "containing", "having" or other variants are intended to cover non-closed inclusion, and no distinction is made between these terms. The term "including" means that other steps and components can be added without affecting the final result. The compositions and methods / processes of the present invention comprise, 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.

[0082] In the present invention, no distinction is made between the terms "efficacy", "performance", "effect", and "function".

[0083] In the description of the embodiments of the present invention, the weight of the relevant components mentioned not only can refer to the specific content of each component, but also can represent the proportional relationship of the weights between the components. Therefore, as long as the content of the relevant components in the description of the embodiments of the present invention is enlarged or reduced in proportion, it is within the scope disclosed in the description of the embodiments of the present invention. Specifically, the weight 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.

[0084] In the present invention, for temperature parameters, unless otherwise specifically defined, both constant temperature treatment and treatment within a certain temperature range are allowed. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. The room temperature described in the present invention refers to 0 - 40°C, preferably 10°C - 35°C, and more preferably 20°C - 30°C. The normal pressure described in the present invention refers to about 1 atm, one atmospheric pressure.

[0085] Unless otherwise mentioned, terms in the singular form may include the plural form and should not be construed as having a quantity of one.

[0086] In addition, the drawings of the present invention are not drawn to a scale of 1:1, and the relative sizes of the components are only drawn by way of example in the drawings for the convenience of understanding the present invention, but not necessarily drawn to the actual scale. The scale in the drawings does not constitute a limitation to the present invention.

[0087] As an excellent transport carrier, nanoemulsions have been widely used in the transport and delivery of fat-soluble functional substances. Compared with traditional anionic nanoemulsions, cationic nanoemulsions have good adsorption and slow-release properties, can play a role of retention and slow release in the skin, can continuously release functional ingredients for a long time, and can better exert skin care effects. How to design and simply prepare cationic nanoemulsions with high stability and high encapsulation rate is a challenge faced by current nanoemulsion technology. The traditional nanoemulsion production method requires single-factor or orthogonal experiments on the nanoemulsion formula and production parameters according to the characteristics of the loaded functional substances to determine the final preparation method. This process takes a long time, consumes a large amount of manpower and material resources, and for the variety of oil-soluble functional substances on the market, continuously changing the production methods and parameters in production also increases the production cost.

[0088] Therefore, the present invention provides a cationic pre-nanoemulsion with good stability for loading oil-soluble functional substances. On the premise of ensuring the encapsulation rate and stability, the production process of the cationic pre-nanoemulsion of oil-soluble functional substances is optimized to only one step of preparation, greatly reducing the difficulty, requirements and cost of preparation and production, and increasing the repeatability and stability of production.

[0089] The technical solution is as follows:

[0090] A cationic pre-nanoemulsion for loading oil-soluble functional substances, comprising phase A and phase B. Calculated as a percentage of the total mass of the nanoemulsion (based on a mass of 100%), it is mainly made of raw materials with the following mass percentages:

[0091] Phase A (oil phase):

[0092]

[0093] Phase B (aqueous phase):

[0094] Non-ionic surfactant 2% - 6%,

[0095] Polyol 2% - 6%,

[0096] Water 62% - 84.67%;

[0097] The positive charge inducer is phytosphingosine;

[0098] The non-ionic surfactant is one or more of cetostearyl alcohol polyether-25, cetyl alcohol polyether-20, behenyl alcohol polyether-25, and stearyl alcohol polyether-21.

[0099] Understandably, based on the mass percentage of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances contains 10% - 20% of the first oil, including but not limited to 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances contains 15% - 20% of the first oil.

[0100] In one embodiment, the first oil is one or more of triglyceride caprylate / caprate and octyldodecanol. Further, the first oil is a mixture of triglyceride caprylate / caprate and octyldodecanol. Still further, the first oil is a mixture composed of triglyceride caprylate / caprate and octyldodecanol in a mass ratio of 1:1.

[0101] In one embodiment, based on the mass percentage of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances contains 10% of triglyceride caprylate / caprate and 10% of octyldodecanol.

[0102] Understandably, based on the mass percentage of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances contains 1% - 5% of lecithin, including but not limited to 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5% or 5%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances contains 1% - 3% of lecithin.

[0103] As a natural ingredient emulsifier, lecithin has good biocompatibility, can fuse with the lipids of the skin cutin layer, disrupt its bilayer arrangement structure, and promote the transdermal absorption of drugs. In the present invention, the compounding of lecithin with a non-ionic surfactant can improve the strength and viscoelasticity of the interfacial film, reduce the fluidity of the interfacial film, prevent the outward diffusion of the surfactant from the interface, and at the same time, through steric hindrance and electrostatic repulsion, hinder the collision between droplets and improve the physical stability of the nanoemulsion.

[0104] In one embodiment, the lecithin is PC50 soy lecithin.

[0105] Understandably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.3% to 0.8% of a positive charge inducer, including but not limited to 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.75% or 0.8%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.5% to 0.8% of an antioxidant.

[0106] Phytosphingosine is a precursor of ceramides and is also one of the skin lipid components. It has a natural barrier repair function and can also be used as a positive charge inducer to impart positive charges to the pre-nanoemulsion droplets. More importantly, the positive charges induced by phytosphingosine can attract negatively charged cells on the skin surface, improving the permeability of active ingredients such as oil-soluble active substances in the skin. Based on the negatively charged characteristics of the skin stratum corneum, the positive charges can increase the absorption of negatively charged skin to the active ingredients, increase their retention time, and thus improve their bioavailability.

[0107] Understandably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.03% to 0.2% of an antioxidant, including but not limited to 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.075%, 0.08%, 0.09%, 0.1%, 0.13%, 0.15%, 0.16%, 0.18%, 0.19% or 0.2%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 0.03% to 0.1% of an antioxidant.

[0108] In one embodiment, the antioxidant is pentaerythrityl tetrakis(bis-tert-butylhydroxyhydrocinnamate).

[0109] Understandably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 2% to 6% of a nonionic surfactant, including but not limited to 2%, 3%, 4%, 5% or 6%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble active substances contains 2% to 5% of a nonionic surfactant.

[0110] In the present invention, one or more nonionic surfactants among cetostearyl alcohol polyether-25, cetearyl alcohol polyether-20, behenyl alcohol polyether-25, and stearyl alcohol polyether-21 can enhance the skin penetration ability and the ability to fluidize the stratum corneum lipids, thereby enhancing the absorption of active ingredients. By using lecithin in combination with nonionic surfactants, and through the selection of the type and adjustment of the proportion of nonionic surfactants, the present invention improves the strength and viscoelasticity of the interfacial film, reduces the fluidity of the interfacial film, prevents the outward diffusion of surfactants from the interface, and at the same time, through steric hindrance and electrostatic repulsion, hinders the collision between droplets, thereby improving the physical stability of the nanoemulsion.

[0111] Understandably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances contains 2% to 6% of polyols, including but not limited to 2%, 3%, 4%, 5%, or 6%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances contains 4% to 6% of polyols.

[0112] In the present invention, polyols and nonionic surfactants 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, polyols as cryoprotectants can reduce the crystallization temperature of the aqueous phase, thereby preparing a nanoemulsion with good stability under high temperature and freezing conditions.

[0113] In one embodiment, the polyol is a polyol having three or five carbon atoms. Further, the polyol is glycerol.

[0114] Understandably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances contains 62% to 84.67% of water, including but not limited to 62%, 63.9%, 65%, 65.1%, 65.95%, 66%, 67%, 68%, 69%, 70%, 72%, 75%, 77%, 80%, 82%, or 84.67%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances, the cationic pre-nanoemulsion available for encapsulating oil-soluble functional substances contains 65.1% to 78.47% of water.

[0115] In one embodiment, the raw materials further include a preservative, which is 0.05% to 0.15% by mass percentage in the cationic pre-nanoemulsion, including but not limited to 0.05%, 0.06%, 0.07%, 0.075%, 0.08%, 0.09%, 0.1%, 0.13% or 0.15%. Preferably, based on the mass percentage of the cationic pre-nanoemulsion available for encapsulating the oil-soluble active substance, the cationic pre-nanoemulsion available for encapsulating the oil-soluble active substance contains 0.05% to 0.1% of the preservative.

[0116] In one embodiment, the preservative is potassium sorbate.

[0117] In one embodiment, the raw materials further include a pH regulator, which is 0.5% to 2% by mass percentage in the cationic pre-nanoemulsion, including but not limited to 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% and 2%.

[0118] In one embodiment, the pH regulator is citric acid.

[0119] In one embodiment, the cationic pre-nanoemulsion available for encapsulating the oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0120] Phase A:

[0121]

[0122] Phase B:

[0123] Non-ionic surfactant 2% - 5%,

[0124] Polyol 4% - 6%,

[0125] Water 65.1% - 78.47%.

[0126] In one embodiment, the cationic pre-nanoemulsion available for encapsulating the oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0127] Phase A:

[0128]

[0129] Phase B:

[0130]

[0131] In one embodiment, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly prepared from the following raw materials in mass percentages:

[0132] Phase A:

[0133]

[0134] Phase B:

[0135]

[0136]

[0137] In one embodiment, the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is mainly prepared from the following raw materials in mass percentages:

[0138] Phase A:

[0139]

[0140] Phase B:

[0141]

[0142] The above-mentioned cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances is a light yellow milky liquid with a faint blue opalescence. This cationic pre-nanoemulsion can encapsulate a variety of oil-soluble active substances, with a high encapsulation efficiency, good stability, and the pre-nanoemulsion has good sustained-release performance, capable of continuously releasing active ingredients or substances for a long time. When used in cosmetics, it can better exert skin care effects.

[0143] Test results show that the particle size of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances in the embodiments of the present invention is 70 nm to 200 nm, the PDI is 0.05 to 0.25, and the pH is 4.5 to 7.0. After being placed at -15°C and 45°C for 3 months, the particle size shows no obvious change. Further, the particle size of the pre-nanoemulsion is 70 to 130 nm, and the PDI is 0.1 to 0.2. Furthermore, the encapsulation efficiency of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances for oil-soluble active substances is above 80%, and some can reach above 95%.

[0144] The present invention also provides a preparation method of the above-mentioned cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, including the following steps:

[0145] Mix the first oil, lecithin, positive charge inducer, and antioxidant to prepare a Phase A mixture;

[0146] Mix the non-ionic surfactant, polyol, and water to prepare a Phase B mixture;

[0147] Mix the A-phase mixture with the B-phase mixture and prepare the primary emulsion through the first atmospheric pressure homogenization treatment.

[0148] Conduct the first high-pressure homogenization treatment on the primary emulsion.

[0149] In one embodiment, the preparation method of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances as described above includes the following steps:

[0150] Under the condition of 100°C to 110°C, dissolve the positive charge inducer in the first oil, and after the solution becomes clear and transparent, cool it down to 40°C to 60°C, and add the lecithin and the antioxidant to prepare the A-phase mixture.

[0151] Under the condition of 40°C to 60°C, mix the non-ionic surfactant, the polyol and the water to prepare the B-phase mixture.

[0152] Add the B-phase mixture to the A-phase mixture and prepare the primary emulsion through the first atmospheric pressure homogenization treatment.

[0153] After the primary emulsion is cooled to room temperature, conduct the first high-pressure homogenization treatment on the primary emulsion to prepare the cationic pre-nanoemulsion.

[0154] In one embodiment, the rate of the first atmospheric pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 5 min to 15 min.

[0155] 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.

[0156] In one embodiment, the preparation method of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances includes the step of mixing a preservative and / or a pH regulator with the cationic pre-nanoemulsion.

[0157] In one embodiment, the preparation method of the cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances includes the following steps a to d:

[0158] Step a: Dissolve the positive charge inducer in the oil phase, stir until the solution is clear, and then add other components of the oil phase to prepare the oil phase mixture.

[0159] Further, dissolve the positive charge inducer in the oil, and after the solution becomes clear and transparent, add other components of the A phase: emulsifier and antioxidant, to prepare the oil phase solution. Preferably, mix and stir to dissolve at a temperature of 100°C to 110°C.

[0160] Step b: Mix and dissolve the non-ionic surfactant, polyol and deionized water to prepare an aqueous phase mixture.

[0161] Further, mix and stir to dissolve at a temperature of 40°C to 60°C until the solution is clear and transparent.

[0162] Step c: Homogenize the aqueous phase and slowly pour the oil phase into the aqueous phase for homogenization to prepare a primary emulsion.

[0163] Preferably, the homogenization rate is 4000 - 8000 rpm and the homogenization time is 5 - 10 min.

[0164] Step d: After the primary emulsion is cooled, it is subjected to high-pressure homogenization to prepare a pre-nanoemulsion.

[0165] Preferably, the pressure of high-pressure homogenization is 300 bar - 900 bar.

[0166] Preferably, the number of high-pressure homogenization times is 3 - 9 times.

[0167] In a specific example, the preparation method further includes step e: adding a preservative and / or a pH regulator to the pre-nanoemulsion prepared in step d and dispersing evenly.

[0168] The present invention also provides a nanoemulsion encapsulating an oil-soluble active substance, comprising a second oil, an oil-soluble active substance, and the cationic pre-nanoemulsion as described above that can be used to encapsulate the oil-soluble active substance.

[0169] In one embodiment, by mass percentage, the nanoemulsion encapsulating an oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0170] Second oil 5% - 20%;

[0171] Oil-soluble active substance 0.05% - 2%; and

[0172] Cationic pre-nanoemulsion that can be used to encapsulate the oil-soluble active substance 78% - 94.95%.

[0173] In one embodiment, by mass percentage, the nanoemulsion encapsulating an oil-soluble active substance is mainly made of raw materials with the following mass percentages:

[0174] Second oil 5% - 20%;

[0175] Oil-soluble active substance 0.5% - 2%; and

[0176] Cationic pre-nanoemulsion that can be used to encapsulate the oil-soluble active substance 78% - 94.5%.

[0177] In one embodiment, the second oil is one or more of triglyceride caprylate / caprate and octyldodecanol. Further, the first oil is a mixture of triglyceride caprylate / caprate and octyldodecanol. Still further, the first oil is a mixture composed of triglyceride caprylate / caprate and octyldodecanol in a mass ratio of 1:1.

[0178] In one embodiment, the oil-soluble efficacy substance is selected from one or more of HPR, 377, and glabridin.

[0179] The present invention also provides a method for preparing the nanoemulsion loaded with the oil-soluble efficacy substance as described above, comprising the following steps:

[0180] Mix the second oil, the oil-soluble efficacy substance, and the cationic pre-nanoemulsion that can be used to load the oil-soluble efficacy substance as described above, and perform a second normal pressure homogenization treatment and a second high-pressure homogenization treatment.

[0181] In one embodiment, the rate of the second normal pressure homogenization treatment is 4000 rpm to 8000 rpm, and the time is 4 min to 7 min.

[0182] 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 3 min to 15 min, and the number of times is 3 to 9 times.

[0183] The present invention also provides a cosmetic, which comprises the cationic pre-nanoemulsion that can be used to load the oil-soluble efficacy substance as described above, or the nanoemulsion loaded with the oil-soluble efficacy substance as described above.

[0184] In one embodiment, the cosmetic is selected from one or more of a facial mask, skin care lotion, essence, spray, and emulsion.

[0185] In one embodiment, the cosmetic is an essence, and the essence comprises the cationic pre-nanoemulsion that can be used to load the oil-soluble efficacy substance as described above.

[0186] In one embodiment, the mass percentage of the cationic pre-nanoemulsion that can be used to load the oil-soluble efficacy 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 cationic pre-nanoemulsion that can be used to load the oil-soluble efficacy substance in the essence is 30% to 50%.

[0187] 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.

[0188] In one embodiment, by mass percentage, the essence contains the following components: 20% - 60% of a cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances, 3% - 5% of glycerol, 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 hydroxyacetophenone, and the balance is deionized water.

[0189] The present invention also provides a preparation method of the above-mentioned essence, including the following steps:

[0190] After dispersing AVC in 30% - 50% of water, add glycerol, butanediol, pentanediol, hydroxyacetophenone, EDTA-2Na, and polyglyceryl-10 myristate, and raise the temperature 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 cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances and mix evenly, and make up water to 100% after cooling to room temperature.

[0191] In one embodiment, the cosmetic is an essence, and the essence includes the nanoemulsion encapsulating oil-soluble active substances as described above.

[0192] In one embodiment, the mass percentage of the nanoemulsion encapsulating oil-soluble active substances in the essence is 20% - 60%, including but not limited to 20%, 30%, 40%, 50% or 60%. Preferably, the mass percentage of the nanoemulsion encapsulating oil-soluble active substances in the essence is 30% - 50%.

[0193] In one embodiment, the essence further includes one or more of a humectant, an ion chelating agent, a thickening agent, a preservative, and an emollient.

[0194] In one embodiment, by mass percentage, the essence contains the following components: 20% - 60% of a nanoemulsion encapsulating oil-soluble active substances, 3% - 5% of glycerol, 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 hydroxyacetophenone, and the balance is deionized water.

[0195] The present invention also provides a preparation method of the above-mentioned essence, including the following steps:

[0196] After dispersing AVC in 30% - 50% water, add glycerol, butanediol, pentanediol, p-hydroxyacetophenone, EDTA-2Na, polyglyceryl-10 myristate, heat 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 nanoemulsion loaded with oil-soluble active substances and mix evenly, and add water to 100% after cooling to room temperature.

[0197] The following will describe the implementation schemes of the present application in detail in combination 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, give priority to referring to the guidance given in the present application, 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.

[0198] In the following specific embodiments, for the measurement parameters of raw material components, if there is no special description, there may be slight deviations within the weighing accuracy range. For temperature and time parameters, acceptable deviations caused by instrument test accuracy or operation accuracy are allowed.

[0199] In the following embodiments, the polyol is glycerol, the antioxidant is pentaerythritol tetrakis(bis-tert-butylhydroxyhydrocinnamate), and the preservative is potassium sorbate.

[0200] Example 1

[0201] Prepare Samples 1 - 5 according to the raw material ratios in Table 1. Under stirring, dissolve the positive charge inducer in the oil phase at 100°C, stir until the solution is clear, cool down to 50°C, and then add other components of the oil phase and stir until clear to obtain the oil phase; add the water phase components to deionized water in turn, heat to 50°C, and stir until the solution is clear and transparent; homogenize the water phase at 50°C at 8000 rpm, and slowly pour it into the oil phase, then homogenize at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion cools down to room temperature, perform high-pressure homogenization treatment, with a pressure of 700 bar, 3 min each time, and a total of 5 times of high-pressure homogenization to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion drops to room temperature, add 0.5% - 2% citric acid to adjust the pH to 5.5.

[0202] Table 1

[0203]

[0204]

[0205] As can be seen from Table 1, the type of surfactant was adjusted to provide sufficient interfacial film strength to stabilize the nanoemulsion system. When the emulsifier was a mixture of 1% PC50 soy lecithin and 4% non-ionic surfactant, and the polyol content was 6% glycerol, the physical stability was good. The prepared cationic pre-nanoemulsion was screened with the conditions of Zeta potential > 30 mV, PDI < 0.3, and small particle size. Among the initial values, the potential of cetostearyl alcohol polyether-20 was slightly higher than the latter, and the particle size and PDI of stearyl alcohol polyether-21 were better than the former. Combining the results of stability investigation, stearyl alcohol polyether-21 was preferably selected as the non-ionic surfactant.

[0206] Example 2

[0207] Samples 1 to 5 were prepared according to the raw material ratios in Table 2. Under stirring, the positive charge inducer was dissolved in the oil phase at 100 °C, stirred until the solution was clear, cooled to 50 °C, and then other components of the oil phase were added and stirred until clear to obtain the oil phase; the components of the aqueous phase were added to deionized water in turn, heated to 50 °C, and stirred until the solution was clear and transparent; the aqueous phase was homogenized at 8000 rpm at 50 °C, slowly poured into the oil phase, and then homogenized at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion was cooled to room temperature, high-pressure homogenization treatment was carried out at a pressure of 700 bar for 3 min each time, and a total of 5 high-pressure homogenizations were carried out to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion dropped to room temperature, 0.5% - 2% citric acid was added to adjust the pH to 5.5.

[0208] Table 2

[0209]

[0210]

[0211] As can be seen from Table 2, as the concentration of the non-ionic surfactant increases, the particle size of the cationic nanoemulsion gradually decreases, and basically remains unchanged after increasing to 6%, but the PDI shows an obvious increase. Within the acceptable growth range of the PDI, the mass percentage of stearyl alcohol polyether-21 in the cationic pre-nanoemulsion was preferably 4%.

[0212] Example 3

[0213] Samples 1 to 6 were prepared according to the raw material ratios in Table 3. Under stirring conditions, the positive charge inducer was dissolved in the oil phase at 100 °C, stirred until the solution was clear, cooled to 40 - 60 °C, and then other components of the oil phase were added and stirred until clear to obtain the oil phase; the components of the aqueous phase were added successively to deionized water, heated to 40 - 60 °C, and stirred until the solution was clear and transparent; the aqueous phase was homogenized at 8000 rpm at 50 °C, slowly poured into the oil phase, and then homogenized at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion was cooled to room temperature, high-pressure homogenization treatment was carried out at a pressure of 700 bar for 3 min each time, and a total of 5 high-pressure homogenizations were performed to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion dropped to room temperature, 0.5% - 2% citric acid was added to adjust the pH to 5.5.

[0214] Table 3

[0215]

[0216] As can be seen from Table 3, as the concentration of the positive charge inducer phytosphingosine increases, the particle size of the cationic nanoemulsion shows a slightly insignificant increase, and the Zeta potential increases significantly until 0.6% and then remains basically unchanged. Therefore, 0.6% is preferably selected as the concentration of the positive charge inducer.

[0217] Example 4

[0218] Samples 1 to 3 were prepared according to the raw material ratios in Table 4. Under stirring conditions, the positive charge inducer was dissolved in the oil phase at 100 °C, stirred until the solution was clear, cooled to 50 °C, and then other components of the oil phase were added and stirred until clear to obtain the oil phase; the components of the aqueous phase were added successively to deionized water, heated to 50 °C, and stirred until the solution was clear and transparent; the aqueous phase was homogenized at 8000 rpm at 50 °C, slowly poured into the oil phase, and then homogenized at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion was cooled to room temperature, high-pressure homogenization treatment was carried out at a pressure of 700 bar for 3 min each time, and a total of 5 high-pressure homogenizations were performed to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion dropped to room temperature, 0.5% - 2% citric acid was added to adjust the pH to 5.5.

[0219] Table 4

[0220]

[0221] As can be seen from Table 4, compared with the pre-nanoemulsion with an oil content of 20%, the Zeta potential of the pre-nanoemulsions with oil contents of 10% and 15% decreased more after being placed at room temperature for 20 days, and the Zeta potential of the pre-nanoemulsion with an oil content of 20% decreased the least. Therefore, the preferred oil content of the pre-nanoemulsion is 20%.

[0222] Example 5

[0223] Prepare samples according to the raw material ratios of the orthogonal test factors and levels in Table 5.

[0224] Under stirring conditions, dissolve the positive charge inducer in the oil phase at 100 °C, stir until the solution is clear, cool down to 50 °C, then add other components of the oil phase and stir until clear to obtain the oil phase; sequentially add the aqueous phase components to deionized water, heat to 50 °C, and stir until the solution is clear and transparent; homogenize the aqueous phase at 8000 rpm at 50 °C, slowly pour it into the oil phase, and then homogenize at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion cools down to room temperature, perform high-pressure homogenization treatment at a pressure of 700 bar for 3 min each time, and perform high-pressure homogenization 5 times in total to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion drops to room temperature, add 0.5% - 2% citric acid to adjust the pH to 5.5. Among them, the oil phase ratio is set at three ratios according to the different solubilities of phytosphingosine in octyldodecanol and GTCC.

[0225] Table 5

[0226]

[0227] Table 6

[0228]

[0229]

[0230] Analysis of the test results in Table 7 --- Comprehensive balance method

[0231]

[0232] For different indicators, the influence degrees of different factors are different. Obtain the comprehensive optimal scheme through the comprehensive balance method. The specific balance process is as follows:

[0233] Factor A: For the Zeta potential index, A is the most important factor and should be considered emphatically when determining the optimal level. Therefore, A1 is preferred.

[0234] Factor B: B is the most important factor for particle size, and B3 is preferred.

[0235] Factor C: According to the importance degree of the indicators: particle size > potential, C2 is preferred.

[0236] Factor D: For both indicators, D2 is the best level.

[0237] Based on the above analysis, the optimal solution is A1B3C2D2, that is, lecithin 1%, steareth-21 4%, glycerol 6%, oil phase ratio 1:1, namely octyldodecanol content is 10%, triglyceride caprylate / caprate 10%, lecithin 1%, glycerol 6%, Tween 80 4%, phytosphingosine 0.6%, potassium sorbate 0.1%,) which can prepare a cationic nanoemulsion with the highest Zeta potential, the smallest particle size and good stability.

[0238] Example 6

[0239] This example provides a cationic pre-nanoemulsion for encapsulating oil-soluble active substances, specifically as follows:

[0240]

[0241] Under stirring, dissolve the positive charge inducer in the oil phase at 100 °C, stir until the solution is clear, cool to 50 °C, then add other components of the oil phase and stir until clear to obtain the oil phase; add the water phase components to deionized water in sequence, heat to 5 °C, and stir until the solution is clear and transparent; homogenize the water phase at 8000 rpm at 50 °C, and slowly pour it into the oil phase, then homogenize at 8000 rpm for 5 min to obtain the primary emulsion; after the primary emulsion cools to room temperature, perform high-pressure homogenization treatment according to Table 8, the pressure range is 300 bar to 900 bar, each time for 3 min, and perform high-pressure homogenization 5 times in total to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion drops to room temperature, add 0.5% - 2% citric acid to adjust the pH to 5.5.

[0242] Table 8

[0243] Sample 1 Sample 2 Sample 3 Sample 4 High-pressure homogenization pressure / bar 300 500 700 900 Particle size / nm 180.8 148.8 108.3 99.27 PDI 0.139 0.123 0.119 0.167

[0244] As can be seen from Table 8, when adjusting the high-pressure homogenization pressure for preparing the pre-nanoemulsion, with the increase of pressure, the particle size and PDI of the prepared pre-nanoemulsion gradually decrease. The particle size data at 700 bar and 900 bar are similar, but the PDI at 900 bar pressure increases more. Considering the increased requirements for equipment and process, 700 bar is preferably selected as the preparation condition.

[0245] Example 7

[0246] This example provides a cationic pre-nanoemulsion for encapsulating oil-soluble active substances, specifically as follows:

[0247]

[0248] Under stirring, the positive charge inducing agent is dissolved in the oil phase at 100°C, stirred until the solution is clear, cooled to 50°C, and then other components of the oil phase are added and stirred until the solution is clear to obtain the oil phase; the aqueous phase components are added to the deionized water in sequence, heated to 50°C, and stirred until the solution is clear and transparent; the aqueous phase is homogenized at 8000rpm at 50°C, and the oil phase is slowly poured into it, and then homogenized at 8000rpm for 5-15min to obtain the colostrum; after the colostrum is cooled to room temperature, it is subjected to high-pressure homogenization treatment according to Table 9, with a pressure of 700bar, each time for 3min, and a total of 3-9 high-pressure homogenizations to obtain the cationic pre-nanoemulsion; after the temperature of the cationic pre-nanoemulsion is reduced to room temperature, 0.5%-2% citric acid is added to adjust the pH to 5.5.

[0249] Table 9

[0250] Sample 1 Sample 2 Sample 3 Sample 4 Number of high-pressure homogenization times 3 5 7 9 Particle size / nm 138.2 116.4 110.9 101.4 PDI 0.122 0.116 0.132 0.139

[0251] It can be seen from Table 9 that by adjusting the number of high-pressure homogenization times when preparing the pre-nanoemulsion, as the pressure increases, the particle size of the prepared pre-nanoemulsion gradually decreases, and the PDI of all samples is <0.3, but it is not stable enough, and there is an upward trend after the number is greater than 5 times. Considering that the increase in the number of high-pressure homogenization times also increases the process difficulty, 5 times of high-pressure homogenization is preferably used as the preparation condition.

[0252] Example 8

[0253] The cationic pre-nanoemulsion sample 3 prepared in Example 7 was used to encapsulate the functional substances, as follows:

[0254] 1 g of oil-soluble functional substance was dissolved in 10 g of GTCC, and 100 g of cationic pre-nanoemulsion was taken. After mixing, the mixture was homogenized at 6000 rpm for 5 min, and then subjected to high-pressure homogenization at 700 bar for 3 min each time. A total of 5 high-pressure homogenizations were performed to obtain cationic nanoemulsions containing different oil-soluble functional substances.

[0255] The encapsulation efficiency of each cationic nanoemulsion loaded with oil-soluble functional substances prepared in Example 8 was tested as follows:

[0256] Take a certain amount of nanoemulsion sample, add 5mL of methanol, mix and sonicate for 15 minutes, and then make up to 10mL. Take a certain amount of demulsified sample and dilute it 5 times, measure the absorbance, and calculate the total content of the corresponding substance, recorded as W1. Then filter 1mL of nanoemulsion through a 0.22μm filter membrane 3 times, transfer 100μL of the sample after the membrane, add 5mL of methanol, mix and sonicate for 15 minutes, and then make up to 10mL. Take a certain amount of demulsified sample and dilute it 5 times, measure the absorbance, and calculate the encapsulation content of the corresponding substance, recorded as W2. The calculation formula is as follows:

[0257]

[0258] The results are shown in Table 10 below.

[0259] Table 10

[0260] Raw material Sample 1 Sample 2 Sample 3 Oil-soluble active substance 377 HPR Glabridin Entrapment efficiency (%) 84.74±0.01 92.80±0.07 95.55±0.13

[0261] Example 9

[0262] This example provides an essence containing a positively charged pre-nanoemulsion prepared from Sample 2 of Example 7, and the ingredient ratio is shown in Table 11.

[0263] Table 11

[0264]

[0265] Preparation method:

[0266] 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 cationic pre-nanoemulsion of Sample 2 of Example 7 and mix evenly, and make up the water to 100%.

[0267] Example 10

[0268] This example provides an essence containing a positively charged pre-nanoemulsion loaded with glabridin prepared from Sample 3 of Example 8, and the ingredient ratio is shown in Table 12.

[0269] Table 12

[0270]

[0271] The preparation method is as follows:

[0272] 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 cationic nanoemulsion loaded with glabridin of Sample 3 of Example 8 and mix evenly, and make up the water to 100%.

[0273] Comparative Example 1

[0274] Comparative Example 1 provides a nanoemulsion and its preparation method, which is substantially the same as that of Example 5, except that it is not subjected to high-pressure homogenization treatment.

[0275] This emulsion is a milky yellow viscous liquid with a particle size of 660 nm. After standing for three days, it shows upper and lower layers. The upper layer is milky white and the lower layer is a light yellow turbid liquid.

[0276] Comparative Example 2

[0277] Comparative Example 2 provides a nanoemulsion, which is substantially the same as Sample 2 of Example 7, except that no positive charge inducer is added.

[0278] This emulsion is a common anionic nanoemulsion, and its particle size distribution and PDI value are similar to those of the cationic nanoemulsion.

[0279] Comparative Example 3

[0280] Comparative Example 3 provides a nanoemulsion, which is basically the same as Sample 3 of Example 8, except that no positive charge inducer is added. This emulsion is a common negatively charged glabridin nanoemulsion, and its particle size distribution and PDI value are similar to those of the positively charged glabridin nanoemulsion.

[0281] Experimental Example 1 Investigation of the stability of nanoemulsion

[0282] Sample 2 of Example 7 and Sample 3 of Example 8 were respectively placed under the conditions of daily, 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 13.

[0283] Table 13

[0284]

[0285]

[0286] Experimental Example 2 Comparative investigation of the stability of essence

[0287] Stability tests were carried out on the cationic prenanoemulsion prepared from Sample 2 of Example 7, and the essences containing the cationic prenanoemulsion of Sample 2 of Example 7 and the cationic glabridin nanoemulsion of Sample 3 of Example 8 prepared in Examples 9 and 10.

[0288] A certain amount of the sample was pipetted into the sample bottle of the Turbiscan Lab stability analyzer to measure the dynamic change of the essence stability. The parameter settings were to scan once every 30 min for 24 h. For the experimental results of Sample 2 of Example 7, see Figure 2 、 3 , generally, it is considered that when the average value of the backscattered light intensity is less than 0.2, the system is in an absolutely stable state. The average value of the backscattered light intensity △BS of this system is 0.03, indicating good stability at room temperature. From the kinetic stability index (TSI) of the two, the smaller the TSI index, the better the stability. It can be seen from this that the cationic nanoemulsion applied to the essence matrix has good stability and can be simply and stably applied to the cosmetic formula. For the experimental results of Example 9, see Figure 4 、 5, the average value of the backscattered light intensity △BS = 0.1, indicating good stability at room temperature. See the experimental results of Example 10 in Figure 6 、 7 , the average value of the backscattered light intensity △BS = 0.14, indicating good stability at room temperature.

[0289] Experimental Example 3 Observation of the Morphology of Cationic Pre-Nanoemulsion by TEM

[0290] The cationic pre-nanoemulsion prepared from Sample 2 of Example 7 was subjected to TEM detection.

[0291] Weigh the sample prepared from Sample 2 of Example 7 and drop it on the copper mesh. After a few seconds, gently pick up the copper mesh sample with forceps, and absorb the excess liquid along one side with filter paper. After it is slightly dried, place the copper mesh on a drop of 2% phosphotungstic acid staining solution 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 on the filter paper with the film side up to dry, and observe and take pictures with a transmission electron microscope. The results are as Figure 8 shown. The TEM images obtained by diluting the emulsion 10 times and 5 times respectively show that the particles are spherical-like and the distribution is relatively uniform.

[0292] Experimental Example 4 Comparative Analysis of In Vitro Skin Permeability and Retention

[0293] The transdermal experiment was carried out in a Franz diffusion cell device. The abdominal skin of guinea pigs was fixed between the receiving cell and the supply cell (the inner layer of the skin faced the receiving cell). The effective permeation area of the skin was 1.77 cm 2 , the volume of the receiving cell was 12 mL, and the magnetic stirring speed in the receiving chamber was 300 r / min. The receiving cell was filled with a release medium of 2% Tween 80 - 20% propylene glycol - physiological saline to remove air bubbles, the stirring was started, and the temperature was kept constant at (37.0 ± 0.5) °C. Samples (with the same content of the active ingredient in the samples) were evenly applied to the skin surface. At 24 h, 1 mL of the sample was taken with a sampling needle and placed in an ep tube. Then, the receiving cell was first evacuated of air bubbles by pulling with a non-porous puncture needle, and then 1 mL of isothermal receiving liquid was added to the receiving cell. The concentration of the lipophilic active substance in the receiving liquid filtered through a 0.22 μm filter membrane was measured by HPLC. The cumulative permeation amount of the active ingredient in 24 h was calculated.

[0294] The cumulative transdermal amount per unit area of the lipophilic active substance was calculated according to the following formula:

[0295]

[0296] In the formula: Qn: the cumulative permeation amount per unit area at the nth time point (μg / cm 2 )

[0297] Cn: Concentration of the active substance in the receiving solution (μg / mL) at the nth sampling time point;

[0298] Cn-1: Concentration of the active substance in the receiving solution (μg / mL) at the (n - 1)th sampling time point;

[0299] V0: Volume of the receiving solution in the receiving pool (mL);

[0300] S: Effective area of the diffusion cell (cm 2 );

[0301] V: Volume of each sampling (1 mL);

[0302] After 24 h, the skin was removed, and the residual sample solution on the surface of the mouse skin was washed off with ultrapure water. Then the mouse skin was cut into pieces and placed in a 10 mL ep tube. 3 mL of methanol was added, and the mixture was sonicated for 30 min. After sonication, it was centrifuged at 5000 rpm for 10 min. The supernatant was taken and the content of the liposoluble active substance was determined by HPLC method, which was the retention amount (Qs) of the active substance in the skin.

[0303] Qs = VC / A

[0304] In the formula: A is the effective diffusion area (1.76625 cm 2 ), V is the total volume of the skin extract (3 mL), and C is the concentration of the active substance in the skin extract.

[0305] The transdermal tests were carried out on the samples of Example 8 and Comparative Example 3 of the present invention. For the test results, see Figure 9 、 10 . From Figure 9 、 10 the in vitro skin cumulative permeation amount and skin retention amount of the samples of Example 8 and Comparative Example 3, it can be seen that the skin permeation amounts per unit area of the samples of Example 8 and Comparative Example 3 at 24 h are respectively: 9.61129 ± 0.90369 μg / cm 2 and 8.90445 ± 0.61192 μg / cm 2 . The skin retention amounts per unit area at 24 h are respectively: anionic glabridin nanoemulsion 0.64348 ± 0.02289 μg / cm 2 、cationic glabridin nanoemulsion 0.64537 ± 0.00367 μg / cm 2 . It can be seen that the permeation amount of the cationic nanoemulsion is higher than that of the ordinary anionic nanoemulsion, which is increased by 1.08 times respectively, and the retention amounts are almost the same. It shows that the cationic nanoemulsion can electrostatically adsorb with cells to improve the permeability of the active substance, and can solve the problems of insufficient transdermal penetration of the anionic nanoemulsion and difficulty for the active substance to reach the deep layer of the skin.

[0306] 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 described in this specification.

[0307] The above-described embodiments only express 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 present invention patent shall be subject to the appended claims.

Claims

1. A cationic 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: Phase B: Non-ionic surfactant 2% - 6%, Polyol 2% - 6%, Water 62% - 84.67%; The positive charge inducer is phytosphingosine; The non-ionic surfactant is one or more of cetearyl alcohol polyether-25, cetyl alcohol polyether-20, behenyl alcohol polyether-25, and stearyl alcohol polyether-21.

2. The cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances according to claim 1, characterized in that, It is mainly made of raw materials with the following mass percentages: Phase A: Phase B: Non-ionic surfactant 2% - 5%, Polyol 4% - 6%, Water 65.1% - 78.47%.

3. The cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances according to claim 1, characterized in that, Meet one or more of the following conditions (1) - (4): (1) The first oil is one or more of triglyceride caprylic / capric acid and octyldodecanol; (2) The lecithin is PC50 soy lecithin; (3) The antioxidant is pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate); (4) The polyol is glycerol.

4. The cationic pre-nanoemulsion for encapsulating oil-soluble active substances according to any one of claims 1 to 3, characterized in that, Meet one or more of the following conditions (1) - (2): (1) The raw materials also include a preservative, with a mass percentage of 0.05% - 0.15% in the cationic pre-nanoemulsion; (2) The raw materials also include a pH regulator, with a mass percentage of 0.5% - 2% in the cationic pre-nanoemulsion.

5. The cationic pre-nanoemulsion according to claim 4, which is used for encapsulating oil-soluble active substances, is characterized in that, Meet one or more of the following conditions (1) - (2): (1) The preservative is potassium sorbate; (2) The pH regulator is citric acid.

6. The cationic pre-nanoemulsion for encapsulating oil-soluble active substances according to any one of claims 1 to 3, characterized in that, The particle size is 70nm - 200nm, PDI is 0.05 - 0.25, and pH is 4.5 - 7.

0.

7. A method for preparing a cationic 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 oil, lecithin, positive charge inducer, 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 the first atmospheric pressure homogenization treatment; Conduct the first high-pressure homogenization treatment on the primary emulsion.

8. The preparation method of the cationic 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 100°C - 110°C, dissolve the positive charge inducer in the first oil. After the solution becomes clear and transparent, cool it to 40°C - 60°C, and add the lecithin and the antioxidant to prepare the Phase A mixture; Under the condition of 40°C - 60°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 treatment; After the primary emulsion cools to room temperature, conduct the first high-pressure homogenization treatment on the primary emulsion to prepare the cationic pre-nanoemulsion.

9. The preparation method of the cationic pre-nanoemulsion according to claim 7 or 8, which can be used for encapsulating oil-soluble active substances, is characterized in that, Meet one or more of the following conditions (1) - (2): (1) The rate of the first atmospheric pressure homogenization treatment is 4000rpm - 8000rpm, and the time is 5min - 15min; (2) The pressure of the first high-pressure homogenization treatment 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 cationic pre-nanoemulsion capable of encapsulating oil-soluble active substances according to claim 7 or 8, characterized in that, It also includes the step of mixing the preservative and / or the pH regulator with the cationic 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 a cationic pre-nanoemulsion as described in any one of claims 1 to 6 that can be used to encapsulate the oil-soluble active ingredient.

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% - 2%; and The cationic pre-nanoemulsion that can be used to encapsulate the oil-soluble active ingredient: 78% - 94.95%.

13. The nanoemulsion encapsulating an oil-soluble active substance according to claim 11 or 12, characterized in that, It satisfies one or more of the following conditions (1) - (2): (1) The second oil is one or more of triglyceride caprylate / caprate and octyldodecanol; (2) The oil-soluble active ingredient is selected from one or more of HPR, 377, and glabridin.

14. A method for preparing the nanoemulsion loaded with 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 cationic pre-nanoemulsion as described in any one of claims 1 to 6 that can be used to encapsulate the oil-soluble active ingredient, 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 satisfies 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 3 min - 15 min, and the number of times is 3 - 9 times.

16. A cosmetic, characterized in that, It includes the cationic pre-nanoemulsion as described in any one of claims 1 to 6 that can be used to encapsulate the oil-soluble active ingredient, or the nanoemulsion encapsulating the oil-soluble active ingredient as described in 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, serums, sprays, and lotions.

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