Ultra-nano packaging system and preparation method thereof

Abstract

The present invention provides an ultra-nano encapsulation system and a preparation method thereof. The preparation method comprises: blending an active ingredient solution with an auxiliary agent to form a mixed colostrum, and then subjecting the mixed colostrum to a specific homogenization treatment to obtain the ultra-nano encapsulation system of the active ingredient; the solute of the active ingredient solution is selected from pharmaceutical active substances or cosmetic active ingredients; the solvent of the active ingredient solution comprises: caprylic / capric triglyceride or isopentyl glycol. The ultra-nano encapsulation system is prepared by the preparation method, and its particle size is less than or equal to 30 nm. The ultra-nano encapsulation system preparation technology route provided by the present invention is reasonable, the effect is outstanding, and it has high repeatability. The ultra-nano encapsulation system prepared by the present invention has the advantages of extremely small system particle size, small PDI, strong room temperature accelerated stability, strong high temperature accelerated stability, and active ingredients are not easy to precipitate, etc., and is particularly suitable for the fields of medicine, cosmetics, and skin care products.

Description

Technical Field

[0001] The invention belongs to the technical field of active ingredient encapsulation system preparation, and in particular relates to an ultra-nano encapsulation system and a preparation method thereof. Background Art

[0002] Liposomes are bilayer vesicles with a structure similar to biological membranes that are made by encapsulating drugs with lecithin, cholesterol, etc. as membrane materials. They have significant advantages in drug delivery systems. The particle size of the system can be controlled to reach the micrometer or even nanometer scale through different processes, formulations, and equipment parameter adjustments. It is a thermodynamically stable system. Compared with traditional encapsulation systems, liposome encapsulation systems have great advantages: small amounts of surfactants are added and irritation is low; the scale and release rate can be flexibly adjusted according to different application environments, and environmental factors such as temperature, humidity, and salinity have little effect on liposome encapsulation systems. The preparation of liposome systems often requires two steps, namely: adjustment of system components and formulations and energy injection homogenization treatment. Among them, the common energy injection homogenization preparation methods include high shear homogenization, ultrasonic homogenization, high pressure homogenization, colloid milling, etc., but they all have disadvantages. For example, the PDI and particle size of liposomes prepared by high shear homogenization are large, and there are huge differences between groups; the liposomes prepared by ultrasonic homogenization have the disadvantages of being time-consuming and energy-intensive, and are difficult to scale up for production; the colloid milling method easily destroys the particles and aggregates near the interface of the liposome emulsion, resulting in uneven droplets and larger particle size.

[0003] The Biopharmaceutics Classification System (BCS) classifies bioactive substances into four types based on the solubility and intestinal permeability of the compounds: Class I is highly soluble / highly permeable substances, Class II is low soluble / highly permeable substances, Class III is high soluble / low permeable substances, and Class IV is low soluble / low permeable substances. Most active ingredients in the cosmetic field are hydrophobic compounds, namely BCS Class II and BCS Class IV compounds. Generally, the bioavailability of such compounds is mainly limited by solubility and dissolution rate in an aqueous environment, and even a small increase in solubility can significantly improve the bioavailability of such compounds.

[0004] Therefore, developing an ultra-nano encapsulation system and its preparation technology with strong solubility, small particle size, small PDI, and water-soluble and fully transparent properties will have broad application prospects and great practical value in the field of nanoformulations. Summary of the invention

[0005] The object of the present invention is to provide an ultra-nano packaging system and a preparation method thereof to solve the above problems.

[0006] In order to achieve the above objectives, the present invention particularly adopts the following technical solutions:

[0007] A method for preparing an ultra-nano encapsulation system, comprising: blending an active ingredient solution with an adjuvant to form a mixed colostrum, and then subjecting the mixed colostrum to a specific homogenization treatment to obtain the ultra-nano encapsulation system of the active ingredient;

[0008] The solute of the active ingredient solution is selected from pharmaceutical active substances or cosmetic active ingredients;

[0009] The solvent of the active ingredient solution includes caprylic / capric triglyceride or isopentyl glycol.

[0010] Preferably, the solute of the active ingredient solution includes one or more of tetrahydrocurcumin, 4-butylresorcinol, peptide anamido, guaiacyl, and bakuchiol-hydroxypropyl tetrahydropyrantriol.

[0011] Preferably, the auxiliary agent includes: one or more of a bilayer film former, a thickener, a membrane fluidity regulator, an antioxidant, glycerol, and ultrapure water.

[0012] The blending comprises the following steps:

[0013] S1: After first mixing the active ingredient solution and the antioxidant, heating in a water bath, stirring and dissolving at a rotation speed of 750-850 rpm under an inert atmosphere to obtain phase A; the antioxidant includes one or more of VC-IP, A alcohol derivatives, and VE derivatives;

[0014] Preferably, the temperature of the first water bath heating is 35-50°C;

[0015] The stirring and dissolving treatment under an inert atmosphere is to prevent some bilayer film-forming agents from being affected by oxidation during pilot production and large-scale production. The oxidation effect is relatively small in the laboratory preparation stage, but the temperature rises rapidly during pilot production and large-scale production, and the specific surface area of ​​the solution system in the production kettle is larger than that in the laboratory container. At this time, the oxidation effect is more serious. Obvious oxidation will lead to the loss of phosphatidylcholine (PC), the active ingredient of the bilayer film-forming agent, resulting in a poorer overall encapsulation effect, which will increase the particle size of the system, increase the PDI, and reduce the encapsulation rate.

[0016] S2: After the bilayer film-forming agent and glycerol are mixed for the second time, they are heated in a water bath for the second time, and then stirred and dispersed for the second time at a rotation speed of 14000-16000 rpm, and then kept warm in a water bath at 50-70° C. to obtain phase B for standby use; the bilayer film-forming agent includes soybean lecithin and / or hydrogenated lecithin;

[0017] Preferably, the temperature of the second water bath heating is 50-70°C;

[0018] Furthermore, a membrane fluidity regulator is also added during the second mixing; more preferably, the membrane fluidity regulator includes: one or more of hexyldecanol, octyldodecanol, squalane, and ultrapure water;

[0019] S3: mixing the thickener and ultrapure water for the third time at room temperature and then stirring for the third time at a rotation speed of 300-500 rpm to obtain phase C; the thickener comprises one or more of hydrogenated phosphatidylcholine, panthenol, and hydroxypropyl tetrahydropyrantriol;

[0020] S4: The phase A obtained in S1, the phase B obtained in S2 and the phase C obtained in S3 are mixed and sheared and homogenized for the fourth time at a rotation speed of 14000-16000 rpm to obtain the mixed colostrum.

[0021] Preferably, the specific homogenization process comprises subjecting the mixed colostrum to an ultra-high pressure homogenization process at a pressure of 20,000-30,000 psi.

[0022] Further preferably, the specific homogenization treatment further comprises: subjecting the sub-nano emulsion obtained by the ultra-high pressure homogenization treatment to a microfluidization homogenization treatment at a pressure of 20000-30000 psi.

[0023] The amount of the antioxidant used in step S1 of the present invention should be not less than 0.1% by mass percentage of the ultra-nano encapsulation system. The reason is that the subsequent steps of the present invention will use a mixture of solid lipids and liquid lipids with large differences in chemical structure. This type of composition will cause more lattice defects in the fluidized layer film of the liposome, and crystallization will still cause the active ingredients to be squeezed out of the ultra-nano encapsulation system. Therefore, the present invention selects a specific amount of antioxidant to compound the system, and can prepare an ultra-nano encapsulation system that is still liquid but not crystallized at room temperature, low temperature and high temperature, that is, a non-crystalline ultra-nano encapsulation system.

[0024] The present invention also provides an ultra-nano encapsulation system, which is prepared by the preparation method; preferably, the particle size of the ultra-nano encapsulation system is less than or equal to 30 nm.

[0025] The pre-treatment schemes used in conventional encapsulation systems are mostly high shear homogenization and ultrasonic homogenization. The traditional microfluidization homogenization method generates severe heat during the preparation process, which easily leads to a large PDI of liposomes. The system with a large PDI is very easy to condense during storage. The condensation will increase the particle size of the system, which is not conducive to storage and transdermal absorption, and the efficacy will also decrease accordingly during actual use. The high shear homogenization method mainly subjects the material to a strong shearing effect, so that the particles are repeatedly subjected to strong impact, collision, friction and shearing, and finally achieve the purpose of crushing. However, the high shear homogenization method is usually carried out in intermittent stirring reactors such as beakers and reactors, and the reaction time is generally long. It is difficult to control the rapid and uniform mixing of the reactants during the process, which may lead to poor dispersion of colostrum, poor repeatability, and difficulty in accurately controlling the microscopic morphology. This mixing process simultaneously significantly affects the parameters such as the particle size, PDI, bilayer film-forming speed and stability of the reaction product. Especially for the thermosensitive system that needs to complete the reaction as soon as possible, the rapid and stable mixing effect has a decisive influence on the smooth progress of the reaction, the yield and quality of the product. The high-pressure homogenizer is a refined pre-treatment instrument that produces strong shear, collision and cavitation effects under high pressure, so that the material can be refined and evenly mixed in the homogenizing valve. Compared with the traditional high-shear homogenization method, ultra-high pressure homogenization can form a chaotic or turbulent state of fluid at the energy contact reaction point. Unlike the intermittent stirring reactors such as beakers and reactors commonly used in high-shear homogenization, the high-pressure homogenizer reaction chamber has a complex geometric structure inside, which makes the flow direction of the fluid constantly change in the mixer, and the fluid is stretched and twisted, increasing the contact area of ​​different fluids. Compared with the high-shear homogenization method, it can quickly improve the mixing efficiency of the fluid, so that the fluids participating in the reaction can be evenly mixed in a shorter time. The smaller size of the reaction cavity inside the reaction chamber can greatly reduce the mixing time. Compared with the intermittent stirring reactor, the micro-mixing reactor greatly shortens the molecular diffusion distance and increases the contact surface area between the fluids, making it easier to achieve a uniform mixing state.

[0026] Microfluidization homogenization can be directly used for the preparation of nanoliposomes, but microfluidization homogenization technology still has the disadvantage of generating high temperature during the preparation process, and its actual application in the processing of cosmetic raw materials is not as extensive as that of high-pressure homogenization. The traditional single microfluidization homogenization method generates severe heat during the preparation process, which can easily cause excessive PDI. Systems with large PDI are very likely to condense during storage, which will increase the particle size of the system and is not conducive to storage and transdermal absorption, and the efficacy will also decrease accordingly during actual use.

[0027] The specific homogenization treatment provided by the present invention: the "ultra-high pressure homogenization-micro-jet homogenization" micro-mixing reaction process technology can make the particle size of the final product reach less than 30nm when performing the preparation of nano-inclusions due to its high mixing efficiency and mixing performance. Therefore, the specific reaction parameters in the encapsulation system provided by the present invention should be adjusted according to the thermal sensitivity and viscosity of different formulas. The structure of the encapsulation system provided by the present invention does not have a large number of hydroxyl groups pointing outward like the conventionally used cyclodextrin, which makes its solubility in aqueous solution far worse than cyclodextrin, and its solubility in organic solvents is even negligible, so it needs to be accompanied by a stirring procedure. At the same time, after a lot of research and experimental verification, it was found that the solubility is greatly affected by the mixing process. Specifically for this application, the solubility of the system will change significantly with the different order of use of the mixing process. When using the "ultra-high pressure homogenization-micro-jet homogenization" micro-mixing reaction process technology, the system will form a relatively stable host-guest complex and significantly improve the solubility of the overall complex in aqueous solution. In addition, under acidic conditions, a large number of free hydrogen ions in the solution of the encapsulation system provided by the present invention will form hydrogen bonds with its carbonyl group, which can also lead to an increase in its solubility. When applied in the field of cosmetics, the specific homogenization treatment provided by the present invention: "Ultra-high pressure homogenization-micro-jet homogenization" micro-mixing reaction process technology can achieve unexpected technical effects when preparing ultra-nano encapsulation systems.

[0028] Beneficial effects of the present invention:

[0029] The preparation method of the ultra-nano encapsulation system provided by the present invention comprises the following steps: a bilayer film-forming agent, a liposome bilayer membrane flow mosaic regulator, and an active ingredient composition dissolved in an active ingredient solvent are first prepared into a sub-nano emulsion, and the pre-treated sub-nano emulsion can prepare an ultra-nano encapsulation system more simply and efficiently than a traditional micron emulsion and a sub-micron emulsion. Compared with traditional micron emulsions and sub-micron emulsions, the ultra-nano encapsulation system prepared after the sub-nano emulsion treatment has a smaller particle size and PDI, and is more convenient for industrial production.

[0030] The ultra-nano encapsulation system provided by the present invention has the advantages of extremely small system particle size, small PDI, strong room temperature accelerated stability, strong high temperature accelerated stability, and active ingredients not easy to precipitate, and can reduce costs and increase efficiency while maintaining efficacy. It can be added to a variety of cosmetic systems of different types and application functions, and has broad development prospects for efficient sustained-release transdermal drug delivery carriers and skin care products industries. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 The particle size and PDI diagram of the ultra-nano encapsulation system provided in Example 1;

[0033] Figure 2 The particle size and PDI diagram of the ultra-nano encapsulation system provided in Example 2;

[0034] Figure 3 The particle size and PDI diagram of the ultra-nano encapsulation system provided in Example 3;

[0035] Figure 4 The particle size and PDI diagram of the ultra-nano encapsulation system provided in Example 4;

[0036] Figure 5 The particle size and PDI diagram of the ultra-nano encapsulation system provided in Example 5;

[0037] Figure 6 The particle size and PDI graph of the encapsulation system provided for Control Example 1;

[0038] Figure 7 Particle size and PDI graph of the encapsulation system provided for Control Example 2;

[0039] Figure 8 Particle size and PDI graph of the encapsulation system provided for Control Example 3;

[0040] Fig. 9 The particle size and PDI graph of the encapsulation system provided for Control Example 4;

[0041] Fig.10 Particle size and PDI graph of the encapsulation system provided for Control Example 5;

[0042] Fig.11 This is a comparison diagram of the promoting effects of Example 1 and Control Example 1 on the relative expression of eln1 gene;

[0043] Fig.12 This is a comparison chart of the inhibitory effects of Example 4 and Control Example 4 on hyaluronidase;

[0044] Fig.13 Atomic force microscope surface morphology and thickness image of the encapsulation system provided in Example 4. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0046] Example 1

[0047] According to the preparation method provided by the present invention, a tetrahydrocurcumin ultra-nano encapsulation system is prepared, which specifically comprises the following steps:

[0048] S1: 5% tetrahydrocurcumin, 5% caprylic / capric triglyceride, 2% VC-IP, 1% A alcohol derivative and 2% VE derivative were heated in a water bath at 40° C. and dissolved by stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0049] S2: 5% soybean lecithin, 2% hexyldecanol, 3% octyldodecyl alcohol, and 40% glycerol were dispersed and dissolved at a rate of 15000 rpm in a 60° C. water bath, and then kept warm in a 60° C. water bath to obtain phase B;

[0050] S3: dissolving and dispersing 3% hydrogenated phosphatidylcholine, 5% panthenol and ultrapure water at room temperature at a rate of 400 rpm by magnetic stirring to obtain phase C;

[0051] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0052] S5: subjecting the mixed colostrum obtained in S4 to ultra-high pressure homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of active ingredients;

[0053] S6: The sub-nano emulsion of the active ingredient obtained in S5 is subjected to microfluidization homogenization at a pressure of 25000 psi, and finally treated by a liposome extruder in series to obtain an ultra-nano encapsulation system of an antioxidant composition containing tetrahydrocurcumin, and the particle size and PDI are shown in the figure. Figure 1 shown.

[0054] Example 2

[0055] According to the preparation method provided by the present invention, a 4-butylresorcinol ultra-nano packaging system is prepared, which specifically comprises the following steps:

[0056] S1: 5% 4-butylresorcinol, 15% caprylic / capric triglyceride, and 5% VC-IP were heated in a water bath at 45° C. and dissolved by stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0057] S2: Disperse and dissolve 5% soybean lecithin and 40% glycerol in a 60°C water bath at a rate of 15000 rpm, and then keep warm in a 60°C water bath to obtain phase B;

[0058] S3: Dissolve and disperse 20% panthenol and ultrapure water under magnetic stirring at room temperature at a rate of 400 rpm to obtain phase C;

[0059] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0060] S5: subjecting the mixed colostrum obtained in S4 to ultra-high pressure homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of active ingredients;

[0061] S6: The sub-nano emulsion of the active ingredient obtained in S5 is subjected to microfluidization homogenization at a pressure of 25000 psi, and finally treated by a liposome extruder in series to obtain a whitening composition ultra-nano encapsulation system containing 4-butylresorcinol, and its particle size and PDI are shown in the figure. Figure 2 shown.

[0062] Example 3

[0063] According to the preparation method provided by the present invention, a peptide Anmido ultra-nano encapsulation system is prepared, which specifically comprises the following steps:

[0064] S1: Heat 1% peptide Anmido, 15% isopentyl glycol, and 5% VC-IP in a water bath at 45°C, and dissolve them with stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0065] S2: 3% hydrogenated lecithin, 20% glycerol, 20% squalane and 10% ultrapure water were dispersed and dissolved at a rate of 15000 rpm in a 60°C water bath, and then kept in a 60°C water bath to obtain phase B;

[0066] S3: Dissolve and disperse 20% panthenol and ultrapure water under magnetic stirring at room temperature at a rate of 400 rpm to obtain phase C;

[0067] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0068] S5: subjecting the mixed colostrum obtained in S4 to ultra-high pressure homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of active ingredients;

[0069] S6: The sub-nano emulsion of active ingredients obtained in S5 is subjected to microfluidization homogenization at a pressure of 25,000 psi, and finally treated by a series of liposome extruders to obtain an ultra-nano encapsulation system of a jaundice-removing composition containing peptide Anmido. The particle size and PDI are shown in the figure below. Figure 3 shown.

[0070] Example 4

[0071] According to the preparation method provided by the present invention, a guaiazulene ultra-nano encapsulation system is prepared, which specifically comprises the following steps:

[0072] S1: 4% guaiazulene, 5% caprylic / capric triglyceride, 2% VC-IP, 1% A alcohol derivative and 2% VE derivative were heated in a water bath at 40° C. and dissolved by stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0073] S2: 5% soybean lecithin, 2% hexyldecanol, 3% octyldodecyl alcohol, and 40% glycerol were dispersed and dissolved at a rate of 15000 rpm in a 60° C. water bath, and then kept warm in a 60° C. water bath to obtain phase B;

[0074] S3: 0.1% aloesin, 3% hydrogenated phosphatidylcholine, 5% panthenol and ultrapure water were dissolved and dispersed by magnetic stirring at a speed of 400 rpm at room temperature to obtain phase C;

[0075] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0076] S5: subjecting the mixed colostrum obtained in S4 to ultra-high pressure homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of active ingredients;

[0077] S6: The sub-nano emulsion of active ingredient obtained in S5 is subjected to microfluidization homogenization treatment at a pressure of 25000 psi, and finally treated by a series of liposome extruders to obtain a soothing, anti-inflammatory and repairing composition ultra-nano encapsulation system containing guaiacylglycerol. The particle size and PDI are shown in the figure below. Figure 4 shown.

[0078] Example 5

[0079] According to the preparation method provided by the present invention, a bakuchiol-hydroxypropyl tetrahydropyrantriol ultra-nano encapsulation system is prepared, which specifically comprises the following steps:

[0080] S1: 5% bakuchiol, 15% caprylic / capric triglyceride, and 5% VC-IP were heated in a water bath at 45° C. and dissolved by stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0081] S2: Disperse and dissolve 5% soybean lecithin and 40% glycerol in a 60°C water bath at a rate of 15000 rpm, and then keep warm in a 60°C water bath to obtain phase B;

[0082] S3: 15% panthenol, 5% hydroxypropyl tetrahydropyrantriol and ultrapure water are dissolved and dispersed by magnetic stirring at a rate of 400 rpm at room temperature to obtain phase C;

[0083] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0084] S5: subjecting the mixed colostrum obtained in S4 to ultra-high pressure homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of active ingredients;

[0085] S6: The sub-nano emulsion of active ingredients obtained in S5 is subjected to microfluidization homogenization at a pressure of 25000 psi, and finally treated by a series of liposome extruders to obtain an ultra-nano encapsulation system of an anti-aging and anti-wrinkle composition containing bakuchiol and hydroxypropyl tetrahydropyrantriol, and its particle size and PDI are shown in the figure Figure 5 shown.

[0086] Comparative Example 1

[0087] A tetrahydrocurcumin nano-encapsulation system is prepared, which specifically comprises the following steps:

[0088] S1: 5% tetrahydrocurcumin, 5% caprylic / capric triglyceride, 2% VC-IP, 1% A alcohol derivative and 2% VE derivative were heated in a water bath at 40° C. and dissolved by stirring at a rate of 800 rpm under an inert atmosphere to obtain phase A;

[0089] S2: 5% soybean lecithin, 2% hexyldecanol, 3% octyldodecyl alcohol, and 40% glycerol were dispersed and dissolved at a rate of 15000 rpm in a 60° C. water bath, and then kept warm in a 60° C. water bath to obtain phase B;

[0090] S3: 0.1% aloesin, 3% hydrogenated phosphatidylcholine, 5% panthenol and ultrapure water were dissolved and dispersed by magnetic stirring at a speed of 400 rpm at room temperature to obtain phase C;

[0091] S4: mixing and shearing homogenizing the phase A obtained in S1, the phase B obtained in S2, and the phase C obtained in S3 at a rate of 15000 rpm to obtain a mixed colostrum;

[0092] S5: The mixed colostrum obtained in S4 is subjected to microfluidization homogenization treatment at a pressure of 25,000 psi, and finally treated by a series of liposome extruders to obtain an antioxidant composition nano-encapsulation system containing tetrahydrocurcumin.

[0093] Comparative Example 2

[0094] A 4-butylresorcinol nano-encapsulation system is prepared, which specifically comprises the following steps:

[0095] S1: Same as Example 2;

[0096] S2: Same as Example 2;

[0097] S3: Same as Example 2;

[0098] S4: Same as Example 2;

[0099] S5: The mixed colostrum obtained in S4 is subjected to ultra-high pressure homogenization treatment at a pressure of 25,000 psi, and finally treated by a series of liposome extruders to obtain a whitening composition nano-encapsulation system containing 4-butylresorcinol.

[0100] Comparative Example 3

[0101] A peptide Anmido nano-encapsulation system was prepared. The difference between its preparation steps and those of Example 3 is that in this control example S5, the mixed colostrum obtained in S4 was processed by a colloid mill at a pressure of 25,000 psi, and finally processed by a series of liposome extruders to obtain a nano-encapsulation system of a jaundice-removing composition containing the peptide Anmido.

[0102] Comparative Example 4

[0103] A guaiacyl sub-nano encapsulation system was prepared. The preparation steps were different from those in Example 4 in that, in this control example S5, the mixed colostrum obtained in S4 was treated by an ultrasonic homogenizer at a pressure of 25,000 psi, and finally treated by a liposome extruder connected in series to obtain a sub-nano encapsulation system of a soothing, anti-inflammatory and repairing composition containing guaiacyl.

[0104] Comparative Example 5

[0105] A bakuchiol-hydroxypropyl tetrahydropyrantriol nano-encapsulation system was prepared. The preparation steps were different from those in Example 5 in that first, in this comparative example S5, the mixed colostrum obtained in S4 was subjected to microfluidization homogenization at a pressure of 25,000 psi to obtain a sub-nano emulsion of the active ingredient;

[0106] Secondly, in this control example S6, the active ingredient sub-nano emulsion obtained in S5 was subjected to ultra-high pressure homogenization treatment at a pressure of 25,000 psi, and finally treated with a series of liposome extruders to obtain a sub-nano encapsulation system of an anti-aging and anti-wrinkle composition containing bakuchiol and hydroxypropyl tetrahydropyrantriol.

[0107] The particle size and PDI diagrams of the systems obtained in Comparative Examples 1-5 are as follows: Figure 6 , Figure 7 , Figure 8 , Fig. 9 and Fig.10 shown.

[0108] The parameters of the products obtained in the embodiments and control examples are shown in Table 1 below:

[0109] Table 1 Parameter test results of the products obtained in the embodiments and control examples

[0110] project Particle size (nm) PDI Example 1 15.17±0.61 0.207±0.08 Example 2 15.39±0.17 0.231±0.04 Example 3 15.06±0.35 0.217±0.06 Example 4 14.04±1.40 0.091±0.01 Example 5 14.41±1.15 0.149±0.06 Comparative Example 1 82.59±2.52 0.191±0.12 Comparative Example 2 113.52±1.73 0.132±0.26 Comparative Example 3 131.83±2.22 0.140±0.99 Comparative Example 4 229.24±3.01 0.251±0.42 Comparative Example 5 288.52±7.66 0.472±0.11

[0111] According to the data in Table 1, it can be clearly seen that the preparation method provided by the present invention can significantly reduce the particle size of the ultra-nano encapsulation system. In the actual application process, when the finished product with a smaller particle size is used, its appearance and application effect will be significantly improved. In addition, there is a certain correlation between the application effect and the particle size, which generally shows a trend that the smaller the particle size, the better the effect.

[0112] After particle size test and PDI test verification, the results show that the particle size data of various types of ultra-nano encapsulation systems prepared by the process provided by the present invention are significantly smaller than those of the control group with the same formula, indicating that the probability of system agglomeration of an ultra-nano encapsulation system prepared by this scheme is low during the storage period, and the stability during the storage period is significantly improved and enhanced.

[0113] Fig.11 The following is a comparison chart of the promotion effect of Example 1 and Control Example 1 on the relative expression of eln1 gene. According to the laboratory method, the anti-wrinkle and firming effects of the samples were tested by the laboratory method. The test results show that the relative expression of eln1 gene in Example 1 group reached 1.89, the reaction system was effective, and there was a significant difference compared with the Control Example 1 group (P<0.05), indicating that Example 1 group had better anti-wrinkle and firming effects. Combined with the experimental data, it can be seen that Example 1, as a new type of encapsulation system with both rigid hydrophobic cavity and multi-carbonyl port, has the ability to specifically bind to the positively charged object eln1 gene. Example 1 can strengthen the binding with the object eln1 gene through the effects of hydrophilic-hydrophobic effect, van der Waals force, ion-dipole interaction, and hydrogen bond, and is significantly better than the Control Example 1 group in terms of action pathway and final data expression, so that the anti-aging effect can be enhanced when used.

[0114] Fig.12 The following is a comparison chart of the inhibitory effects of Example 4 and Control Example 4 on hyaluronidase. According to the laboratory method (HMC-WI-029 hyaluronidase inhibition rate), the soothing effect of the sample was tested by the laboratory method; the test results show that the average hyaluronidase inhibition rate of Example 4 is 17.260%, which is significantly different from that of Control Example 4 (P<0.05), indicating that the soothing effect of Example 4 is better than that of Control Example 4. Combined with the experimental data, it can be seen that the molecular port of Example 4 is composed of carbonyl groups, and the large number of carbonyl groups are arranged in a directional manner, which makes the polarity of the port of Example 4 stronger, giving it obvious hydrophilicity. The cavity surrounded by the molecular skeleton composed of a large number of carbon-nitrogen bonds and carbon-carbon bonds is far away from any hydrophilic group, and there is no lone pair of electrons oriented inside the cavity, so that the cavity of Example 4 has extremely strong hydrophobicity, and the enhanced hydrophobicity of the internal cavity can better preserve the activity of the active ingredient, thereby making the soothing effect more obvious.

[0115] Fig.13 The atomic force microscope surface morphology and thickness map of the encapsulation system provided in Example 4 is shown by Fig.13 It can be seen that the surface morphology of the encapsulation system provided in Example 4 under atomic force microscopy is a typical spherical structure. Combining the particle size and PDI test data, it can be shown that Example 4 successfully prepared an ultra-nano encapsulation system.

[0116] The ultra-nano encapsulation system provided by the present invention has an extremely small average particle size, which increases the surface area and reduces the surface charge density, so the absolute value of the Zeta potential tends to zero. It can be seen from the Leckner theoretical model that in actual application, the ultra-nano encapsulation system can show better adhesion to cells than the liposome encapsulation system, and can promote the active ingredients to complete the retention, sustained release and controlled release of cells for a longer time, thereby greatly improving the application effect of the active ingredients. The ultra-nano encapsulation system of the active composition can be added to a variety of cosmetic systems of different types and application functions, and has broad development and application prospects for the high-efficiency sustained-release transdermal drug delivery carrier and the functional skin care product industry.

[0117] Please note that the technical features of the above embodiments can be combined arbitrarily. In order to make the description concise, all possible combinations of the technical features in the above embodiments are not described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification. The above embodiments only express several implementation methods of the present application, and their descriptions are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several variations and improvements can be made, which all belong to the scope of protection of the present application. Therefore, the scope of protection of the patent in this application shall be based on the attached claims.

Claims

1. A method for preparing an ultra-nano encapsulation system, characterized in that: include: The active ingredient solution is blended with the adjuvant to form a mixed colostrum, and then the mixed colostrum is subjected to a specific homogenization treatment to obtain an ultra-nano encapsulation system of the active ingredient; The solute of the active ingredient solution includes one or more of tetrahydrocurcumin, 4-butylresorcinol, peptide anamido, guaiazulene, bakuchiol-hydroxypropyl tetrahydropyrantriol; The solvent of the active ingredient solution includes: caprylic / capric triglyceride or isopentyl glycol; The auxiliary agent includes: one or more of a bilayer film former, a thickener, a film fluidity regulator, an antioxidant, and glycerol; Wherein, the membrane fluidity regulator includes: one or more of hexyldecanol, octyldodecanol, squalane, etc.; The thickener includes one or more of hydrogenated phosphatidylcholine, panthenol, and hydroxypropyl tetrahydropyrantriol; The specific homogenization treatment includes subjecting the mixed colostrum to ultra-high pressure homogenization at a pressure of 20,000-30,000 psi, and then subjecting the sub-nano emulsion obtained by the ultra-high pressure homogenization treatment to microfluidization homogenization at a pressure of 20,000-30,000 psi.

2. The preparation method according to claim 1, characterized in that: The blending comprises the following steps: S1: After first mixing the active ingredient solution and the antioxidant, heating them in a water bath, and first stirring and dissolving them in an inert atmosphere to obtain phase A; S2: mixing the bilayer film-forming agent and glycerol for a second time, heating them in a water bath for a second time, stirring and dispersing them for a second time, and then keeping them warm in a water bath to obtain phase B for use; S3: mixing the thickener and ultrapure water for a third time at room temperature and then stirring for a third time to obtain phase C; S4: The phase A obtained in S1, the phase B obtained in S2 and the phase C obtained in S3 are mixed and sheared and homogenized for the fourth time at a rotation speed of 14000-16000 rpm to obtain the mixed colostrum.

3. The preparation method according to claim 2, characterized in that: The step S1 satisfies one or more of the following conditions: a. The antioxidant comprises one or more of VC-IP, A alcohol derivatives, and VE derivatives; b. The first water bath is heated at a temperature of 35-50 ° C; c. The first stirring speed is 750-850rpm.

4. The preparation method according to claim 2, characterized in that: The step S2 satisfies one or more of the following conditions: d. The bilayer film-forming agent comprises soy lecithin and / or hydrogenated lecithin; e. The second water bath is heated at a temperature of 50-70°C; f. The water bath temperature is 50-70 ° C; g. The second stirring speed is 14000-16000rpm; h. In step S2, a membrane fluidity regulator is also added during the second mixing.

5. The preparation method according to claim 2, characterized in that: The third stirring speed is 300-500 rpm.

6. An ultra-nano packaging system, characterized in that: Prepared by the preparation method according to any one of claims 1 to 5.

7. The ultra-nano packaging system according to claim 6, characterized in that: The particle size of the ultra-nano encapsulation system is less than or equal to 30 nm.

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