Facial cream with efficient transdermal absorption effect and preparation method thereof

Abstract

The invention provides face cream with an efficient transdermal absorption effect and a preparation method of the face cream, and belongs to the technical field of skin care products. Comprising the following components: sweet almond oil, hydrogenated lecithin, sodium lactate, betaine, caprylic / capric triglyceride, glycerol, ceramide, phytosterol, decyl methyl sulfoxide, laurocapram, a liposome-hydrogel compound and purified water. According to the invention, 1, 2-distearoyl-sn glycerol-3-phosphoethanolamine, distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 and cholesteryl hemisuccinate are used as raw materials to prepare an acid-sensitive liposome, and after the acid-sensitive liposome is used for loading a bletilla striata flower extract, a centella asiatica extract and resveratrol which have whitening active ingredients, the acid-sensitive liposome can be used for preparing the whitening mask. According to the invention, the skin barrier can be firstly repaired, inflammatory response is reduced, and after the skin is recovered to a weakly acidic environment, the whitening active ingredients are released, so that the skin can absorb and utilize the whitening active ingredients more easily.

Description

Technical Field

[0001] The invention relates to the technical field of skin care products, and in particular to a facial cream with high-efficiency transdermal absorption effect and a preparation method thereof. Background Art

[0002] As the largest organ in the human body, the skin has a barrier function to protect internal tissues from external damage. As we age, due to the influence of many factors such as gravity, endocrine, and light, the skin will gradually age and deteriorate, causing its elasticity to slowly decrease, and become thinner and looser, thereby weakening its protective effect on internal tissues.

[0003] Facial cream is a skin care product used for facial skin care. It usually contains a variety of nutrients and functional ingredients. It is applied on the face to form a protective film to achieve a variety of skin care effects such as moisturizing, nourishing, repairing, whitening, and anti-wrinkle. However, most skin care active ingredients are difficult to penetrate the stratum corneum to reach the dermis due to their large molecules or the obstruction of the skin barrier, resulting in low transdermal absorption efficiency of facial cream.

[0004] Liposomes can interact with the lipid layer of the skin, change its physical properties, fuse with the lipid layer of the stratum corneum, increase the fluidity of the skin, and thus promote the penetration of active substances. Using liposomes to load large molecular active substances can improve the skin's absorption of large molecular active substances. However, the phospholipid bilayer of liposomes is easily oxidized by oxygen, light or free radicals in the environment, leading to structural disintegration. In addition, there are esterases, phospholipases, etc. on the surface of the skin, which can degrade the phospholipid components and accelerate the rupture of liposomes, causing the liposomes to be quickly cleared from the skin, resulting in a decrease in the skin retention rate of the active ingredients, thereby reducing the transdermal absorption utilization rate of the active ingredients.

[0005] In addition, under normal circumstances, the pH value of the facial skin surface is weakly acidic. When the pH value of the facial skin is unbalanced, its pH value is usually high (i.e. weakly alkaline). At this time, if active ingredients with whitening effects (such as niacinamide) are used directly, it will not only reduce the absorption efficiency of these ingredients, causing their effects to weaken, but also easily induce chemical irritation reactions, leading to sensitive symptoms such as peeling, redness, and itching, thereby further damaging the skin barrier function.

[0006] Based on this, it is necessary to propose a facial cream with efficient transdermal absorption effect and a preparation method thereof, which can improve the skin retention rate of active ingredients and reduce the irritation reaction. Summary of the invention

[0007] In view of the deficiencies in the prior art, the object of the present invention is to provide a facial cream with efficient transdermal absorption effect and a preparation method thereof.

[0008] A method for preparing a facial cream with high-efficiency transdermal absorption efficacy comprises the following steps: S1: After dissolving ethylene glycol chitosan, adding lauryl tetraethylene glycol methacrylate to react to prepare modified chitosan; S2: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, bletilla striata flower extract, niacinamide and α-arbutin were mixed and dissolved to prepare acid-sensitive liposomes; S3: dissolving sodium alginate and the modified chitosan separately and mixing them, and then mixing them with the acid-sensitive liposomes to prepare a liposome-hydrogel complex; S4: Add sweet almond oil, hydrogenated lecithin, sodium lactate, betaine, caprylic / capric triglyceride and glycerin into pure water, heat and stir evenly, and after cooling, add ceramide, phytosterol, decyl methyl sulfoxide, laurocaprol and the above-mentioned liposome-hydrogel complex, stir evenly to obtain a facial cream with high-efficiency transdermal absorption effect.

[0009] Furthermore, S1 specifically includes the following steps: S1.1: Dissolve ethylene glycol chitosan in deionized water at a solid-liquid ratio of 1 g: (90-100) mL, stir thoroughly to dissolve, and then add isopropanol to dilute to twice the original volume to obtain ethylene glycol chitosan solution; S1.2: Add equimolar amounts of ammonium persulfate and tetramethylethylenediamine to the above ethylene glycol chitosan solution, stir and mix thoroughly, then add lauryloxytetraethylene glycol methacrylate, heat and stir under nitrogen at 30-40°C for 8-10h, cool, dialyze and freeze-dry to obtain modified chitosan.

[0010] Furthermore, S2 specifically includes the following steps: S2.1: Add 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, Bletilla striata flower extract, niacinamide and α-arbutin into the mixed solvent at a solid-liquid ratio of 1 mg: (6-8) mL, stir thoroughly to dissolve, and obtain a mixed solution; S2.2: The mixed solution was evaporated at 45-50°C and 20-30 r / min in the dark for 1-2 h, and then PBS buffer was added. The mixture was kept warm and hydrated for 1-2 h, and then ultrasonicated at low temperature and filtered through a 0.45 μm microporous filter membrane to obtain acid-sensitive liposomes.

[0011] Furthermore, S3 specifically includes the following steps: S3.1: Add sodium alginate powder into deionized water to prepare a 6-8 mg / mL sodium alginate solution; S3.2: Add the modified chitosan prepared in step S1.2 into deionized water at a solid-liquid ratio of 1 g: (90-100) mL, stir and mix thoroughly, and add it into the above sodium alginate solution at a volume ratio of 1: (2-3), stir and mix thoroughly, and then add 0.1 mol / L sodium hydroxide solution to adjust the pH to neutral to obtain a thermosensitive hydrogel; S3.3: Add the acid-sensitive liposomes prepared in step S2.2 to the above-mentioned thermosensitive hydrogel, stir and mix evenly to obtain a liposome-hydrogel complex.

[0012] Furthermore, the amount of ammonium persulfate added is 1-3% of the mass of ethylene glycol chitosan, and the mass ratio of lauryl tetraglycol methacrylate to ethylene glycol chitosan is (2-3):1.

[0013] Furthermore, the molar ratio of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate is (18-22):1:(12-14), and the mass ratio of the total mass of the three to the bletilla striata flower extract, niacinamide and α-arbutin is (25-35):(3-5):(1-2):1.

[0014] Furthermore, the mixed solvent is prepared from dichloromethane and methanol in a volume ratio of 1:(1.5-2.5), and the volume ratio of PBS buffer to the mixed solvent is 1:2, and the pH of the PBS buffer is 7.4.

[0015] Furthermore, the mass ratio of the acid-sensitive liposome to the thermosensitive hydrogel is 1:(3-5).

[0016] Furthermore, the facial cream with high-efficiency transdermal absorption effect includes, by mass: 8-10 parts of sweet almond oil, 2-3 parts of hydrogenated lecithin, 1-2 parts of sodium lactate, 0.6-0.8 parts of betaine, 0.8-1 parts of caprylic / capric triglyceride, 2-3 parts of glycerol, 0.1-0.3 parts of ceramide, 0.3-0.5 parts of phytosterols, 0.8-1.2 parts of decyl methyl sulfoxide, 0.6-1.2 parts of laurocapram, 2-3 parts of liposome-hydrogel complex and 70-80 parts of purified water.

[0017] Furthermore, a facial cream with efficient transdermal absorption effect is prepared by any of the above-mentioned methods for preparing a facial cream with efficient transdermal absorption effect.

[0018] Compared with the prior art, the present invention has at least the following beneficial effects: 1. In the present invention, acid-sensitive liposomes are prepared by using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate as raw materials, and the acid-sensitive liposomes are used to load whitening active ingredients such as Bletilla striata flower extract, Centella asiatica extract and resveratrol. When the pH value of facial skin is high, the coating effect of the acid-sensitive liposomes reduces the release of the active ingredients, and the skin barrier is repaired and the inflammatory response is reduced preferentially through ingredients such as ceramide and phytosterols. After the skin is restored to a weakly acidic environment, the whitening active ingredients are released through the acid-sensitive liposomes, thereby being more conducive to the skin's absorption and utilization of the whitening active ingredients, and helping to improve the whitening and spot-removing effects of the whitening active ingredients.

[0019] 2. In the present invention, glycidyl methacrylate is first reacted with chitosan to introduce methacrylic acid groups into chitosan molecules to functionalize them, and then the functionalized chitosan is mixed with lauryl tetraethylene glycol methacrylate to react, and lauryl tetraethylene glycol methacrylate with temperature response function is grafted onto chitosan to modify chitosan to give chitosan temperature-sensitive properties. The modified chitosan is mixed with sodium alginate to form a hydrogel, which is then mixed with acid-sensitive liposomes. When the hydrogel contacts facial skin, the temperature rises to promote gelation of the hydrogel, and combines with polar groups on the skin surface to form a tightly fitting interface, thereby reducing the shedding of the acid-sensitive liposomes caused by friction or sweat, thereby prolonging the retention time of the acid-sensitive liposomes in the epidermis, which is beneficial to improving the transdermal absorption utilization rate of the whitening active ingredients.

[0020] 3. In the present invention, laurocapram can increase the permeability of fat-soluble components by destroying the regular arrangement of the lipid bilayer of the stratum corneum, while decyl methyl sulfoxide can dissolve the α-helical structure in the keratin of the stratum corneum to form hydrophilic channels, thereby enhancing the permeability of hydrophilic components and reducing the mechanical resistance between keratinocytes by reducing the stability of intercellular adhesion proteins. When the two are used in combination, the lipid pathway and the polar pathway are activated at the same time, achieving full coverage and penetration of lipophilic and hydrophilic components, thereby significantly improving the transdermal absorption efficacy of active ingredients. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The accompanying drawings, which are incorporated herein and constitute a part of the specification, illustrate embodiments of the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable those skilled in the relevant art to make and use the present disclosure.

[0022] Figure 1 This is a cumulative release rate curve of the liposomes prepared in Example 1 of the present invention at pH=5.5 and pH=7.5.

[0023] Figure 2This is a cumulative release rate curve of the liposomes prepared in Comparative Example 1 of the present invention at pH=5.5 and pH=7.5.

[0024] Figure 3 This is a schematic diagram of the state of the liposome-hydrogel complex prepared in Example 1 of the present invention at 25°C.

[0025] Figure 4 This is a schematic diagram of the state of the liposome-hydrogel complex prepared in Example 1 of the present invention at 37°C. DETAILED DESCRIPTION

[0026] The following is a detailed description of a facial cream with efficient transdermal absorption effect and a preparation method thereof provided by the present invention in conjunction with the accompanying drawings and specific embodiments.

[0027] Example 1 A method for preparing a facial cream with high-efficiency transdermal absorption efficacy comprises the following steps: S1: Ethylene glycol chitosan was dissolved in deionized water at a solid-liquid ratio of 1g:90mL, and the mixture was fully stirred and dissolved. Then, isopropanol was added to dilute the mixture to twice the original volume to obtain an ethylene glycol chitosan solution. Then, equimolar amounts of ammonium persulfate and tetramethylethylenediamine were added to the ethylene glycol chitosan solution, and the mixture was fully stirred and mixed. Then, lauryloxytetraethylene glycol methacrylate was added, and the mixture was heated and stirred at 30°C for 8h under the protection of nitrogen. After cooling, the mixture was dialyzed and freeze-dried to obtain modified chitosan, wherein the amount of ammonium persulfate added was 1% of the mass of the ethylene glycol chitosan, and the mass ratio of lauryloxytetraethylene glycol methacrylate to ethylene glycol chitosan was 2:1. S2: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, Bletilla striata flower extract, niacinamide and α-arbutin were added to the mixed solvent at a solid-liquid ratio of 1 mg:6 mL, and the mixture was fully stirred and dissolved to obtain a mixed solution, wherein the molar ratio of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate was 18:1:12 , and the total mass of the three and the mass ratio of the Bletilla striata flower extract, niacinamide and α-arbutin is 25:3:1:1; the mixed solvent is prepared by dichloromethane and methanol in a volume ratio of 1:1.5, and then the mixed solution is rotary evaporated at 45°C and 20r / min in the dark for 1h, and then PBS buffer is added, and the mixture is kept warm and hydrated for 1h, and then ultrasonicated at low temperature and filtered through a 0.45μm microporous filter membrane to obtain acid-sensitive liposomes, wherein the volume ratio of PBS buffer to the mixed solvent is 1:2, and the pH of PBS buffer is 7.4; S3: adding sodium alginate powder to deionized water to prepare a 6 mg / mL sodium alginate solution, then adding the modified chitosan prepared in step S1 to deionized water at a solid-liquid ratio of 1 g:90 mL, stirring and mixing thoroughly, and adding it to the sodium alginate solution at a volume ratio of 1:2, stirring and mixing thoroughly, and then adding 0.1 mol / L sodium hydroxide solution to adjust the pH to neutral to obtain a thermosensitive hydrogel, and then adding the acid-sensitive liposome prepared in step S2 to the above-mentioned thermosensitive hydrogel, stirring and mixing uniformly to obtain a liposome-hydrogel complex, wherein the mass ratio of the acid-sensitive liposome to the thermosensitive hydrogel is 1:3; S4: Add 8 parts by mass of sweet almond oil, 2 parts by mass of hydrogenated lecithin, 1 part by mass of sodium lactate, 0.6 parts by mass of betaine, 0.8 parts by mass of caprylic / capric triglyceride, and 2 parts by mass of glycerol to 70 parts by mass of pure water, heat and stir evenly, and after cooling, add 0.1 parts by mass of ceramide, 0.3 parts by mass of phytosterols, 0.8 parts by mass of decyl methyl sulfoxide, 0.6 parts by mass of laurocapram and 2 parts by mass of the above-mentioned liposome-hydrogel complex, stir evenly, and obtain a facial cream with high-efficiency transdermal absorption effect.

[0028] Example 2 A method for preparing a facial cream with high-efficiency transdermal absorption efficacy comprises the following steps: S1: Ethylene glycol chitosan was dissolved in deionized water at a solid-liquid ratio of 1g:95mL, and the mixture was fully stirred and dissolved. Then, isopropanol was added to dilute the mixture to twice the original volume to obtain an ethylene glycol chitosan solution. Then, equimolar amounts of ammonium persulfate and tetramethylethylenediamine were added to the ethylene glycol chitosan solution, and the mixture was fully stirred and mixed. Then, lauryloxytetraethylene glycol methacrylate was added, and the mixture was heated and stirred at 35°C for 9h under the protection of nitrogen. After cooling, the mixture was dialyzed and freeze-dried to obtain modified chitosan, wherein the amount of ammonium persulfate added was 2% of the mass of the ethylene glycol chitosan, and the mass ratio of lauryloxytetraethylene glycol methacrylate to ethylene glycol chitosan was 2.5:1. S2: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, Bletilla striata flower extract, niacinamide and α-arbutin were added to a mixed solvent at a solid-liquid ratio of 1 mg:7 mL, and the mixture was fully stirred and dissolved to obtain a mixed solution, wherein the molar ratio of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate was 20:1:13, and The total mass of the three and the mass ratio of Bletilla striata flower extract, niacinamide and α-arbutin is 30:4:1.5:1; the mixed solvent is prepared by dichloromethane and methanol in a volume ratio of 1:2, and then the mixed solution is rotary evaporated at 48°C and 25r / min in the dark for 1.5h, and then PBS buffer is added, and the mixture is kept warm and hydrated for 1.5h, and low-temperature ultrasound is performed, and the mixture is filtered through a 0.45μm microporous membrane to obtain acid-sensitive liposomes, wherein the volume ratio of PBS buffer to the mixed solvent is 1:2, and the pH of PBS buffer is 7.4; S3: adding sodium alginate powder into deionized water to prepare a 6-8 mg / mL sodium alginate solution, then adding the modified chitosan prepared in step S1 into deionized water at a solid-liquid ratio of 1 g:95 mL, stirring and mixing thoroughly, and adding the chitosan into the sodium alginate solution at a volume ratio of 1:2.5, stirring and mixing thoroughly, and then adding 0.1 mol / L sodium hydroxide solution to adjust the pH to neutral to obtain a thermosensitive hydrogel, and then adding the acid-sensitive liposome prepared in step S2 into the above-mentioned thermosensitive hydrogel, stirring and mixing uniformly to obtain a liposome-hydrogel complex, wherein the mass ratio of the acid-sensitive liposome to the thermosensitive hydrogel is 1:4; S4: Add 9 parts by mass of sweet almond oil, 2.5 parts by mass of hydrogenated lecithin, 1.5 parts by mass of sodium lactate, 0.7 parts by mass of betaine, 0.9 parts by mass of caprylic / capric triglyceride, and 2.5 parts by mass of glycerol to 75 parts by mass of pure water, heat and stir evenly, and after cooling, add 0.2 parts by mass of ceramide, 0.4 parts by mass of phytosterols, 1 part by mass of decyl methyl sulfoxide, 0.9 parts by mass of laurocapram and 2.5 parts by mass of the above-mentioned liposome-hydrogel complex, stir evenly, and obtain a facial cream with high efficient transdermal absorption effect.

[0029] Example 3 A method for preparing a facial cream with high-efficiency transdermal absorption efficacy comprises the following steps: S1: Dissolve ethylene glycol chitosan in deionized water at a solid-liquid ratio of 1g:100mL, stir thoroughly to dissolve, then add isopropanol to dilute to twice the original volume to obtain an ethylene glycol chitosan solution, then add equimolar amounts of ammonium persulfate and tetramethylethylenediamine to the ethylene glycol chitosan solution, stir thoroughly to mix, then add lauryloxytetraethylene glycol methacrylate, heat and stir at 40°C for 10h under the protection of nitrogen, and after cooling, dialyze and freeze-dry to obtain modified chitosan, wherein the amount of ammonium persulfate added is 3% of the mass of ethylene glycol chitosan, and the mass ratio of lauryloxytetraethylene glycol methacrylate to ethylene glycol chitosan is 3:1; S2: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, Bletilla striata flower extract, niacinamide and α-arbutin were added to the mixed solvent at a solid-liquid ratio of 1 mg:8 mL, and the mixture was fully stirred and dissolved to obtain a mixed solution, wherein the molar ratio of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate was 22:1:14 , and the total mass of the three and the mass ratio of the Bletilla striata flower extract, niacinamide and α-arbutin is 35:5:2:1; the mixed solvent is prepared by dichloromethane and methanol in a volume ratio of 1:2.5, and then the mixed solution is rotary evaporated at 50°C and 30r / min in the dark for 2h, and then PBS buffer is added, and the mixture is kept warm and hydrated for 2h, and then ultrasonicated at low temperature and filtered through a 0.45μm microporous filter membrane to obtain acid-sensitive liposomes, wherein the volume ratio of PBS buffer to the mixed solvent is 1:2, and the pH of PBS buffer is 7.4; S3: adding sodium alginate powder to deionized water to prepare an 8 mg / mL sodium alginate solution, then adding the modified chitosan prepared in step S1 to deionized water at a solid-liquid ratio of 1 g:100 mL, stirring and mixing thoroughly, and adding it to the sodium alginate solution at a volume ratio of 1:3, stirring and mixing thoroughly, and then adding 0.1 mol / L sodium hydroxide solution to adjust the pH to neutral to obtain a thermosensitive hydrogel, and then adding the acid-sensitive liposome prepared in step S2 to the above-mentioned thermosensitive hydrogel, stirring and mixing uniformly to obtain a liposome-hydrogel complex, wherein the mass ratio of the acid-sensitive liposome to the thermosensitive hydrogel is 1:5; S4: Add 10 parts by mass of sweet almond oil, 3 parts by mass of hydrogenated lecithin, 2 parts by mass of sodium lactate, 0.8 parts by mass of betaine, 1 part by mass of caprylic / capric triglyceride, and 3 parts by mass of glycerol to 80 parts by mass of pure water, heat and stir evenly, and after cooling, add 0.3 parts by mass of ceramide, 0.5 parts by mass of phytosterols, 1.2 parts by mass of decyl methyl sulfoxide, 1.2 parts by mass of laurocapram and 3 parts by mass of the above-mentioned liposome-hydrogel complex, stir evenly, and obtain a facial cream with high efficient transdermal absorption effect.

[0030] Comparative Example 1 The difference between this comparative example 1 and example 1 is that the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate in step S2 are replaced by lecithin, hydrogenated lecithin and cholesterol, and the total amount of lecithin, hydrogenated lecithin and cholesterol is equal to the total amount of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate.

[0031] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that step S1 is removed, and the modified chitosan in step S3 is replaced by an equal amount of ethylene glycol chitosan.

[0032] Comparative Example 3 The difference between this comparative example 3 and example 1 is that the laurocapram in step S4 is replaced by an equal amount of decyl methyl sulfoxide.

[0033] Comparative Example 4 The difference between this comparative example 4 and embodiment 1 is that the decyl methyl sulfoxide in step S4 is replaced by an equal amount of laurocapram.

[0034] Test Case Test 1: 1 mL of the liposomes prepared in Example 1 and Comparative Example 1 were loaded into dialysis bags, immersed in PBS buffer (9 mL, 0.1 mol / L, pH = 7.5 or 5.5), and dialyzed continuously in a 37°C water bath. Then, 1 mL of the dialysate was taken at 0.5, 1, 2, 4, 6, 8, 10, and 12 seconds, and 1 mL of PBS buffer was added. The total concentrations of Bletilla striata flower extract, nicotinamide, and α-arbutin at different sampling points were measured, and the cumulative release rate was calculated. Each group was tested three times in parallel, and the average value was taken. The cumulative release rate-time curve was plotted, as shown in FIG. Figure 1 and Figure 2 shown.

[0035] from Figure 1 and Figure 2It can be seen that the 12h cumulative release rate of the liposomes prepared in Example 1 is about 85% under pH = 5.5 environment, and the 12h cumulative release rate under pH = 7.5 environment is only about 40%, while the 12h cumulative release rate of the liposomes prepared in Comparative Example 1 under pH = 5.5 and pH = 7.5 environments is more than 80%, indicating that the liposomes prepared in Example 1 have acid-sensitive properties, and their release rate in a weakly acidic environment is much higher than that in a weakly alkaline environment. It can be seen that by using 1,2-distearoyl- Acid-sensitive liposomes were prepared using sn-glycerol-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate as raw materials. The acid-sensitive liposomes were loaded with Bletilla striata flower extract, Centella asiatica extract and resveratrol, which have whitening active ingredients. When the pH value of facial skin was high, the coating effect of the acid-sensitive liposomes reduced the release of active ingredients, and preferentially repaired the skin barrier through ingredients such as ceramide and phytosterols, reduced inflammatory response, and restored the skin to a weakly acidic environment.

[0036] Test 2: The liposome-hydrogel complexes prepared in Examples 1-3 and Comparative Example 2 were placed in a water bath at 25°C and 37°C, respectively, and the gelation was observed. The results are shown in Table 1. The gelation of the liposome-hydrogel complex prepared in Example 1 is shown in Table 1. Figure 3 and Figure 4 shown.

[0037] Table 1: Gelation of liposome-hydrogel complex 25℃ 37℃ Example 1 Unformed Glue Example 2 Unformed Glue Example 3 Unformed Glue Comparative Example 2 Glue Glue From Table 1, Figure 3 and Figure 4 It can be seen that the liposome-hydrogel complex prepared in Comparative Example 2 does not have a thermosensitive property, and it is a colloid in a high temperature or low temperature environment, while the liposome-hydrogel complexes prepared in Examples 1-3 all have a thermosensitive property. It can be seen that by first reacting glycidyl methacrylate with chitosan, a methacrylic acid group is introduced into the chitosan molecule to functionalize it, and then the functionalized chitosan is mixed with lauryl tetraethylene glycol methacrylate to react, and lauryl tetraethylene glycol methacrylate with a temperature-responsive function is grafted onto chitosan, and the chitosan is modified to give the chitosan a thermosensitive property.

[0038] Test 3: Transdermal Diffusion Test The pre-treated mouse abdomen was depilated and fixed between the dosing pool and the receiving pool of the diffusion pool, and 1g of the cream prepared in Examples 1-3 and Comparative Examples 3-4 was evenly applied on the mouse skin. The receiving solution in the receiving pool was a saline solution of 20% ethanol, and the mouse skin was in full contact with the receiving solution. 1mL of the receiving solution was taken at 8h, and the total content of Bletilla striata flower extract, niacinamide and α-arbutin was determined, and the 8h cumulative permeability was calculated. Each group was tested 3 times in parallel, and the average value was taken. The results are shown in Table 2.

[0039] Table 2: 8h cumulative permeability test results Cumulative permeability (%) Example 1 75.23 Example 2 75.76 Example 3 74.94 Comparative Example 3 65.62 Comparative Example 4 63.48 It can be seen from Table 2 that when single decyl methyl sulfoxide or single laurocapram is used in Comparative Examples 3 and 4, the cumulative permeability is lower than that in the embodiment. It can be seen that when decyl methyl sulfoxide and laurocapram are used in combination, the transdermal absorption efficacy of the active ingredient can be synergistically improved.

[0040] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A method for preparing a facial cream with efficient transdermal absorption, characterized in that: The steps include: S1: After dissolving ethylene glycol chitosan, adding lauryl tetraethylene glycol methacrylate to react to prepare modified chitosan; S2: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, bletilla striata flower extract, niacinamide and α-arbutin were mixed and dissolved to prepare acid-sensitive liposomes; S3: dissolving sodium alginate and the modified chitosan separately and mixing them, and then mixing them with the acid-sensitive liposomes to prepare a liposome-hydrogel complex; S4: Add sweet almond oil, hydrogenated lecithin, sodium lactate, betaine, caprylic / capric triglyceride and glycerin into pure water, heat and stir evenly, and after cooling, add ceramide, phytosterol, decyl methyl sulfoxide, laurocaprol and the above-mentioned liposome-hydrogel complex, stir evenly to obtain a facial cream with high-efficiency transdermal absorption effect.

2. The method for preparing a facial cream with efficient transdermal absorption according to claim 1, characterized in that: S1 specifically includes the following steps: S1.1: Dissolve ethylene glycol chitosan in deionized water at a solid-liquid ratio of 1 g: (90-100) mL, stir thoroughly to dissolve, and then add isopropanol to dilute to twice the original volume to obtain ethylene glycol chitosan solution; S1.2: Add equimolar amounts of ammonium persulfate and tetramethylethylenediamine to the above ethylene glycol chitosan solution, stir and mix thoroughly, then add lauryloxytetraethylene glycol methacrylate, heat and stir under nitrogen at 30-40°C for 8-10h, cool, dialyze and freeze-dry to obtain modified chitosan.

3. The method for preparing a facial cream with efficient transdermal absorption according to claim 2, characterized in that: S2 specifically includes the following steps: S2.1: Add 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoyl phosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, Bletilla striata flower extract, niacinamide and α-arbutin into the mixed solvent at a solid-liquid ratio of 1 mg: (6-8) mL, stir thoroughly to dissolve, and obtain a mixed solution; S2.2: The mixed solution was evaporated at 45-50°C and 20-30 r / min in the dark for 1-2 h, and then PBS buffer was added. The mixture was kept warm and hydrated for 1-2 h, and then ultrasonicated at low temperature and filtered through a 0.45 μm microporous filter membrane to obtain acid-sensitive liposomes.

4. The method for preparing a facial cream with high-efficiency transdermal absorption efficacy according to claim 3, characterized in that: S3 specifically includes the following steps: S3.1: Add sodium alginate powder into deionized water to prepare a 6-8 mg / mL sodium alginate solution; S3.2: Add the modified chitosan prepared in step S1.2 into deionized water at a solid-liquid ratio of 1 g: (90-100) mL, stir and mix thoroughly, and add it into the above sodium alginate solution at a volume ratio of 1: (2-3), stir and mix thoroughly, and then add 0.1 mol / L sodium hydroxide solution to adjust the pH to neutral to obtain a thermosensitive hydrogel; S3.3: Add the acid-sensitive liposomes prepared in step S2.2 to the above-mentioned thermosensitive hydrogel, stir and mix evenly to obtain a liposome-hydrogel complex.

5. The method for preparing a facial cream with efficient transdermal absorption according to claim 2, characterized in that: The amount of ammonium persulfate added is 1-3% of the mass of ethylene glycol chitosan, and the mass ratio of lauryl tetraethylene glycol methacrylate to ethylene glycol chitosan is (2-3):

1.

6. The method for preparing a facial cream with high-efficiency transdermal absorption efficacy according to claim 3, characterized in that: The molar ratio of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol hemisuccinate is (18-22):1:(12-14), and the mass ratio of the total mass of the three to the bletilla striata flower extract, niacinamide and α-arbutin is (25-35):(3-5):(1-2):

1.

7. The method for preparing a facial cream with high-efficiency transdermal absorption efficacy according to claim 3, characterized in that: The mixed solvent is prepared from dichloromethane and methanol in a volume ratio of 1:(1.5-2.5), and the volume ratio of PBS buffer to the mixed solvent is 1:2, and the pH of the PBS buffer is 7.

4.

8. The method for preparing a facial cream with high-efficiency transdermal absorption efficacy according to claim 4, characterized in that: The mass ratio of acid-sensitive liposomes to thermosensitive hydrogel is 1:(3-5).

9. The method for preparing a facial cream with high-efficiency transdermal absorption efficacy according to claim 1, characterized in that: The facial cream with high-efficiency transdermal absorption effect includes, by mass: 8-10 parts of sweet almond oil, 2-3 parts of hydrogenated lecithin, 1-2 parts of sodium lactate, 0.6-0.8 parts of betaine, 0.8-1 parts of caprylic / capric triglyceride, 2-3 parts of glycerin, 0.1-0.3 parts of ceramide, 0.3-0.5 parts of phytosterols, 0.8-1.2 parts of decyl methyl sulfoxide, 0.6-1.2 parts of laurocapram, 2-3 parts of liposome-hydrogel complex and 70-80 parts of purified water.

10. A facial cream with high-efficiency transdermal absorption effect, characterized in that: The facial cream is prepared by the method for preparing a facial cream with high-efficiency transdermal absorption effect as described in any one of claims 1 to 9.

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