Temperature-sensitive liposome as well as preparation method and application thereof

Abstract

The invention discloses a temperature-sensitive liposome as well as a preparation method and application thereof, and belongs to the technical field of cosmetics. The temperature-sensitive liposome comprises phospholipid, a temperature-sensitive material, polyol, an active component and a water phase, wherein the temperature-sensitive material is a binary or ternary eutectic mixture composed of two or three fatty acids. The phase transition temperature of the eutectic system is adjusted to be close to the temperature of a human body by regulating the length and proportion of carbon chains of fatty acid. The active ingredients are uniformly dispersed in the eutectic matrix in an amorphous or molecular state, and form a stable multi-element eutectic structure with fatty acid through intermolecular interaction, so that the stability, the encapsulation efficiency and the drug loading performance of the ingredients are effectively enhanced. The liposome is good in biocompatibility, safe in metabolism, suitable for the field of cosmetics and wide in application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of cosmetics, in particular to a temperature-sensitive liposome and a preparation method and application thereof. BACKGROUND

[0002] Liposomes are bilayer membrane vesicles formed by self-assembly of amphiphilic phospholipid molecules in an aqueous phase, with a unique hydrophobic membrane region and a hydrophilic internal cavity structure, and can simultaneously encapsulate fat-soluble and water-soluble active ingredients, so they are widely used in drugs and cosmetics. To achieve the "on-demand release" of active ingredients, researchers have tried to introduce temperature-responsive materials into the liposome membrane phase to construct temperature-sensitive liposomes to respond to temperature changes and regulate the release behavior of active ingredients.

[0003] Currently, the construction of temperature-sensitive liposomes mainly relies on regulating the phase transition temperature of the liposome wall material. For example, patent CN102210870A discloses a liposome complex phospholipid with adjustable phase transition temperature, which realizes the preparation of liposomes with different phase transition temperatures by adjusting the ratio of dipalmitoylphosphocholine and hydrogenated soybean phospholipid. Patents CN119185205A and CN107997979B respectively disclose a preparation method of a luteolin temperature-sensitive liposome and a temperature-sensitive liposome with whitening effect, which mainly adjusts the ratio of different structure phosphatidylcholine to realize the regulation of temperature-sensitive performance and release rate of active ingredients. In addition, some studies introduce temperature-sensitive materials to endow liposomes with temperature responsiveness. For example, patent CN103211765A discloses a preparation method of drug-loaded temperature-sensitive self-assembled liposomes, which introduces poly-N,N-isopropylacrylamide to make the liposomes have temperature-sensitive response ability by utilizing its phase transition at about 32℃.

[0004] Although temperature-sensitive liposomes have made some progress in the fields of drugs and cosmetics, the existing technology that uses liposome wall material as a temperature-sensitive control means still has problems such as low encapsulation efficiency, limited drug loading capacity, and high risk of burst release, which makes it difficult to meet the needs of high-efficiency loading and stable release of active substances in cosmetics. Therefore, developing a new type of temperature-sensitive material to construct temperature-sensitive liposomes with high encapsulation efficiency, high drug loading capacity, and good stability has become a key problem that needs to be solved in the current cosmetics field. SUMMARY

[0005] The present application aims to provide a temperature-sensitive liposome, a preparation method and application thereof, so as to solve the problems of low encapsulation efficiency, small drug loading capacity and poor stability of the temperature-sensitive liposome in the prior art in cosmetic applications. The liposome takes a binary or ternary fatty acid eutectic system as a temperature-sensitive control core, and by controlling the carbon chain length and proportion of the fatty acid, a responsive system with a phase transition temperature close to the skin temperature of the human body is constructed. The eutectic temperature-sensitive material can produce a synergistic effect with the phospholipid membrane, significantly improving the encapsulation efficiency and drug loading capacity of the liposome on the active ingredient, and at the same time enhancing the structural stability and release controllability of the system, so as to realize the temperature-sensitive release of the active ingredient in the skin.

[0006] The present application provides a temperature-sensitive liposome, which comprises the following components in percentage by mass: Phospholipid 5-10%, Temperature-sensitive material 1-6%, Polyhydric alcohol 10-15%, Active ingredient 5-16%, Aqueous phase 55-75%; The temperature-sensitive material is a binary or ternary eutectic mixture formed by fatty acids.

[0007] Preferably, the phospholipid is selected from one or more of the following: lecithin, hydrogenated lecithin, dicaprylphosphatidylcholine, dilaurylphosphatidylcholine, dimyristylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, 1-palmitoyl-2-ethylphosphatidylcholine, 1-palmitoyl-2-butylphosphatidylcholine, 1-palmitoyl-2-hexanoylphosphatidylcholine, 1-palmitoyl-2-octanoylphosphatidylcholine, 1-palmitoyl-2-decanoylphosphatidylcholine, 1-palmitoyl-2-lauric acylphosphatidylcholine.

[0008] Preferably, the temperature-sensitive material is composed of two or three kinds of fatty acids to form a binary or ternary eutectic mixture; the fatty acids are capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, eicosanoic acid, and docosanoic acid.

[0009] Preferably, the polyhydric alcohol is selected from one or more of the following: 1,4-butanediol, 1,3-propanediol, glycerol, sorbitol, polyethylene glycol, and dipropylene glycol.

[0010] Preferably, the active ingredient is selected from one or more of the following: ascorbic acid, nicotinamide, ceramide, coenzyme Q10, astaxanthin, 4-butylresorcinol, retinol, and tetrahydrocurcumin.

[0011] Preferably, the liposome further comprises a preservative and / or an antioxidant; wherein the preservative is one or more of p-hydroxyacetophenone, 1,2-hexanediol, benzyl alcohol, benzoic acid, imidazole alkyl urea, and the antioxidant is one or more of tocopherol, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole.

[0012] The preparation method of the temperature-sensitive liposome described above comprises the following steps: (1) mixing and heating phospholipid, temperature-sensitive material, polyol, active ingredient, preservative and antioxidant to obtain solution A; (2) mixing solution A and water phase under constant temperature conditions and performing homogenization treatment; (3) performing ultrasonic treatment on the mixture obtained in step (2) to stably embed and uniformly disperse the active ingredient in fatty acid through intermolecular interaction to form an active molecule-fatty acid ternary or multi-component eutectic system, and the eutectic system cooperates with phospholipid to finally obtain the temperature-sensitive liposome.

[0013] Further, the heating temperature in step (1) is 80-90℃.

[0014] Further, the constant temperature conditions in step (2) are 85-95℃, the rotation speed of homogenization is 10000-15000 rpm, and the homogenization time is 10-15 min.

[0015] Further, the ultrasonic treatment in step (3) adopts a probe ultrasonic instrument, the ultrasonic power is 450-500 W, the ultrasonic temperature is 10-15℃, and the ultrasonic time is 10-20 min.

[0016] Preferably, the application of the temperature-sensitive liposome in cosmetics also belongs to the protection scope of the present application.

[0017] In the application, the fatty acid eutectic system cooperates with the phospholipid membrane to realize the temperature-sensitive release of the active ingredient near the temperature of human skin, and to improve the skin care effect and use experience.

[0018] The present application has the following advantages: (1) The present application adopts a binary or ternary fatty acid eutectic mixture as a temperature-sensitive material, adjusts the carbon chain length and the ratio of fatty acid to construct a eutectic system with a low melting point, so that the phase transition temperature can be adjusted to close to the human body temperature (about 37℃). When the temperature is lower than the phase transition temperature, the active ingredient is stably encapsulated in the liposome; when the environmental temperature rises above the phase transition temperature, the fatty acid eutectic mixture changes from solid to liquid, which causes the phospholipid membrane structure to be disordered and damaged, thereby promoting the rupture of the liposome and realizing the rapid and controllable release of the active ingredient.

[0019] (2) The fatty acid cocrystal mixture exhibits excellent encapsulation capacity for hydrophobic active ingredients, significantly improving their solubility and dispersion stability. During melt blending, the active ingredient is uniformly dispersed in the fatty acid matrix, and after cooling and solidification, it is "frozen" in amorphous or molecular form within the solid framework. Furthermore, the active ingredient and fatty acid molecules can form a drug-fatty acid multi-element cocrystal structure through intermolecular forces such as hydrogen bonds and van der Waals forces, further enhancing its stability. This cocrystal system, in synergy with phospholipids, not only improves the dissolution rate of the active ingredient but also effectively enhances the encapsulation efficiency and drug loading of liposomes.

[0020] (3) Fatty acid eutectic mixtures have good biocompatibility while regulating the melting point and lipophilicity of active molecules. Their metabolites are safe and non-toxic, and they are suitable for cosmetics and skin care products. They have high practical value and application prospects. Attached Figure Description

[0021] Figure 1 The appearance of the thermosensitive liposomes prepared in Examples 1-4 and Comparative Examples 1-4 of the present invention after standing at 25°C for 24 hours; Figure 2 The cumulative release curves of active ingredients of the liposomes prepared in Examples 1-4 of this invention at different temperatures are shown. Figure 3 The particle size distribution diagrams are of the liposomes prepared in Examples 1-4 of this invention. Figure 4 The particle size distribution diagrams are for the liposomes prepared in Comparative Examples 1-4 of this invention. Detailed Implementation

[0022] The present invention is further illustrated below by way of examples. These examples are for illustrative purposes only and do not limit the scope of the present invention.

[0023] Example 1 A tranexamic acid thermosensitive liposome, comprising, by weight percentage, 8% dipalmitoylphosphatidylcholine, 10% 1,4-butanediol, 16% tranexamic acid, 1% decanoic acid / stearic acid (mass ratio 9:1), 0.3% p-hydroxyacetophenone, 0.5% ascorbic acid, and 64.2% water.

[0024] A method for preparing tranexamic acid thermosensitive liposomes includes the following steps: (1) Mix dipalmitoylphosphatidylcholine, 1,4-butanediol, tranexamic acid, decanoic acid / stearic acid, p-hydroxyacetophenone, and ascorbic acid at 90°C until completely dissolved to obtain solution A; (2) Under constant temperature of 85℃, homogenize at high speed of 15000rpm, slowly add solution A dropwise to water, and continue homogenizing for 10min after the addition is completed; (3) Transfer the homogenized mixture to a probe sonicator and sonicate it for 20 minutes at 480W and 10℃ to obtain tranexamic acid thermosensitive liposomes.

[0025] Example 2 A nicotinamide thermosensitive liposome, by weight percentage, comprises 5% myristoyl phosphatidylcholine, 10% 1,4-butanediol, 8% nicotinamide, 5% lauric acid / stearic acid (mass ratio 4:1), 0.3% imidazolidinyl urea, 0.3% tocopherol, and 71.4% water.

[0026] A method for preparing nicotinamide thermosensitive liposomes includes the following steps: (1) Mix dimyristoyl phosphatidylcholine, 1,4-butanediol, nicotinamide, lauric acid / stearic acid, imidazolidinyl urea and tocopherol at 85°C until completely dissolved to obtain solution A; (2) Under constant temperature of 90℃, homogenize at high speed of 13000rpm, slowly add solution A dropwise to water, and continue homogenization for 10min after the addition is completed; (3) Transfer the homogenized mixture to a probe sonicator and sonicate it for 10 minutes at 480W and 15℃ to obtain nicotinamide thermosensitive liposomes.

[0027] Example 3 A coenzyme Q10 thermosensitive liposome, comprising, by weight percentage: 8% hydrogenated lecithin, 15% 1,4-butanediol, 10% coenzyme Q10, 6% decanoic acid / lauric acid / linoleic acid (mass ratio 8:3:1), 0.2% benzyl alcohol, 0.3% tocopherol, and 60.5% water.

[0028] The method for preparing coenzyme Q10 thermosensitive liposomes includes the following steps: (1) Hydrogenated lecithin, 1,4-butanediol, coenzyme Q10, decanoic acid / lauric acid / linoleic acid, benzyl alcohol, and tocopherol are mixed at 85°C until completely dissolved to obtain solution A; (2) Under constant temperature of 95℃, homogenize at high speed of 15000rpm, slowly add solution A dropwise to water, and continue homogenizing for 15min after the addition is completed; (3) Transfer the homogenized mixture to a probe sonicator and sonicate it at 480W and 10℃ for 15 minutes to obtain coenzyme Q10 thermosensitive liposomes.

[0029] Example 4 A ceramide thermosensitive liposome, comprising, by weight percentage, 10% 1-palmitoyl-2-lauroyl phosphatidylcholine, 10% 1,4-butanediol, 15% ceramide, 5% myristic acid / stearic acid / eicosanoic acid (mass ratio 10:4:1), 0.3% p-hydroxyacetophenone, 0.5% ascorbic acid, and 59.2% water.

[0030] A method for preparing ceramide thermosensitive liposomes includes the following steps: (1) Mix 1-palmitoyl-2-lauroyl phosphatidylcholine, 1,4-butanediol, ceramide, myristic acid / stearic acid / eicosanoic acid, p-hydroxyacetophenone, and ascorbic acid at 80°C until completely dissolved to obtain solution A; (2) Under constant temperature of 90℃, homogenize at high speed of 12000rpm, slowly add solution A dropwise to water, and continue homogenization for 13min after the addition is completed; (3) Transfer the homogenized mixture to a probe sonicator and sonicate it at 480W and 15℃ for 10 minutes to obtain ceramide thermosensitive liposomes.

[0031] Comparative Example 1 Replace the thermosensitive material decanoic acid / stearic acid with an equal weight of water, and otherwise follow the same procedure as in Example 1.

[0032] Comparative Example 2 The phospholipids in Comparative Example 2 were hydrogenated lysophosphatidylcholine, dipalmitoylphosphatidylcholine, and dimyristoyl lecithin (in a mass ratio of 1:2:1), and the thermosensitive materials decanoic acid / stearic acid were replaced with an equal weight of water. Otherwise, they were the same as in Example 1.

[0033] Comparative Example 3 The phospholipids in Comparative Example 3 were dipalmitoylphosphatidylcholine and hydrogenated soybean phospholipids (mass ratio 1:1), and the thermosensitive materials decanoic acid / stearic acid were replaced with an equal weight of water. Otherwise, they were the same as in Example 1.

[0034] Comparative Example 4 The phospholipids in Comparative Example 4 were dipalmitoylphosphatidylcholine and 1-myristoyl-2-stearoylphosphatidylcholine (mass ratio 1:8), and the thermosensitive materials decanoic acid / stearic acid were replaced with an equal weight of water. Otherwise, they were the same as in Example 1.

[0035] The specific test methods for precipitation stability, particle size, zeta potential value, encapsulation efficiency, and drug loading rate are as follows: Stability test: The liposomes prepared in Examples 1-4 and Comparative Examples 1-4 were formulated into 5% aqueous dispersions, placed at 25°C and allowed to stand. The precipitation time was observed and the test period was 30 days.

[0036] Particle size and Zeta potential test: The liposomes prepared in Examples 1-4 and Comparative Examples 1-4 were diluted 100 times with deionized water, and their particle size and Zeta potential value were measured using a nanoparticle size and Zeta potential meter.

[0037] The content of free active ingredients in the prepared liposomes was determined by high performance liquid chromatography or ultraviolet-visible spectrophotometry. The total active ingredient content was the amount of feed used during liposome preparation. The encapsulation efficiency and drug loading rate were calculated using the following formulas: Encapsulation efficiency (%) = (Total active ingredient content - Free active ingredient content) / Total active ingredient content × 100%; Drug loading rate (%) = (total active ingredient content - free active ingredient content) / phospholipid content × 100%.

[0038] The specific testing method for the content of free active ingredients is as follows: (1) Determination of the content of free active ingredients in tranexamic acid thermosensitive liposomes Tranexamic acid methanol solutions with concentrations of 0.05 mg / mL, 0.06 mg / mL, 0.07 mg / mL, 0.08 mg / mL, and 0.09 mg / mL were prepared, and standard curves were established by high-performance liquid chromatography (HPLC). The HPLC test conditions were as follows: the column packing material was octadecylsilane-bonded silica gel, the column temperature was 30℃, the mobile phase was acetonitrile and 0.1 M ammonium acetate buffer (pH 5.0) at a volume ratio of 25:75, the flow rate was 1 mL / min, and the injection volume was 10 μL; the detection wavelength of the evaporative light scattering detector was 232 nm.

[0039] Mix 1 mL of tranexamic acid thermosensitive liposome sample with 10 mL of petroleum ether, vortex for 5 min, centrifuge at 3000 r / min for 5 min, and collect the supernatant. After drying the supernatant, redissolve it in methanol and bring the volume to 10 mL. Filter the solution through a 0.22 μm microporous membrane and perform high-performance liquid chromatography (HPLC) analysis. Record the peak areas and calculate the content of free active ingredients in the tranexamic acid thermosensitive liposome sample based on the standard curve.

[0040] (2) Determination of the content of free active ingredient in nicotinamide thermosensitive liposomes Nicotinamide methanol solutions with concentrations of 0.02 mg / mL, 0.04 mg / mL, 0.06 mg / mL, 0.08 mg / mL, and 0.10 mg / mL were prepared, and standard curves were established by high-performance liquid chromatography (HPLC). The HPLC test conditions were as follows: the column packing material was octadecylsilane-bonded silica gel, the column temperature was 30℃, the mobile phase was a mixture of 0.02 mol / L potassium dihydrogen phosphate solution and methanol at a volume ratio of 95:5, the flow rate was 1 mL / min, the injection volume was 10 μL, and the detection wavelength of the evaporative light scattering detector was 261 nm.

[0041] Mix 1 mL of nicotinamide thermosensitive liposome sample with 10 mL of petroleum ether, vortex for 5 min, centrifuge at 3000 r / min for 5 min, and collect the supernatant. After drying the supernatant, redissolve it in methanol and bring the volume to 10 mL. Filter the solution through a 0.22 μm microporous membrane and perform high-performance liquid chromatography (HPLC) analysis. Record the peak area and calculate the content of free active ingredient in the nicotinamide thermosensitive liposome sample based on the standard curve.

[0042] (3) Determination of the content of free active ingredients in thermosensitive coenzyme Q10 liposomes Coenzyme Q10 ethanol solutions with concentrations of 0.03 mg / mL, 0.04 mg / mL, 0.05 mg / mL, 0.06 mg / mL, and 0.07 mg / mL were prepared respectively, and the ultraviolet absorbance at 275 nm was measured using a UV-Vis spectrophotometer to establish a standard curve.

[0043] Mix 1 mL of coenzyme Q10 thermosensitive liposome sample with 6 mL of n-pentane, vortex for 5 min, centrifuge at 3000 r / min for 5 min, and collect the supernatant. After drying the supernatant, redissolve it in ethanol and bring the volume to 10 mL. Measure the absorbance using a UV-Vis spectrophotometer, and calculate the content of free active ingredient in the coenzyme Q10 thermosensitive liposome sample according to the standard curve.

[0044] (4) Determination of the content of free active ingredients in ceramide thermosensitive liposomes Ceramide methanol solutions with concentrations of 0.02 mg / mL, 0.03 mg / mL, 0.04 mg / mL, 0.05 mg / mL, and 0.06 mg / mL were prepared, and standard curves were established by high-performance liquid chromatography (HPLC). The HPLC test conditions were as follows: the column packing material was octadecylsilane-bonded silica gel, the column temperature was 25℃, the mobile phase was 100% methanol, the flow rate was 1 mL / min, the injection volume was 20 μL, the drift tube temperature of the evaporative light scattering detector was 75℃, and the nitrogen flow rate was 2 L / min.

[0045] Mix 1 mL of ceramide thermosensitive liposome sample with 5 mL of n-hexane, vortex for 5 min, centrifuge at 3000 r / min for 5 min, and collect the supernatant. After drying the supernatant, redissolve it in methanol and bring the volume to 10 mL. Filter the solution through a 0.22 μm microporous membrane and perform high-performance liquid chromatography (HPLC) analysis. Record the peak area and calculate the content of free active ingredient in the ceramide thermosensitive liposome sample based on the standard curve.

[0046] Table 1: Performance test results of liposomes prepared in Examples 1-4 and Comparative Examples 1-4 As shown in Table 1, the thermosensitive liposomes prepared in Examples 1-4 of this invention are very stable. No solid precipitation occurred after 30 days of storage at 25°C, demonstrating excellent storage stability. The average particle size is less than 110 nm, the Zeta potential is less than -50 mV, the system carries a high negative charge, and the interparticle repulsion is strong, making it difficult to aggregate. The encapsulation efficiency is greater than 98%, and the drug loading rate exceeds 100%. Among them, the drug loading rate of Example 1 is as high as 200%, which is significantly better than conventional liposomes.

[0047] In Comparative Examples 1-4, the liposome carriers used were phospholipid molecules or mixtures of phospholipids that have been reported to have thermosensitive effects. No additional thermosensitive materials were introduced, and their thermosensitive properties mainly originated from the physical properties of the phospholipids themselves. As can be seen from the data in Table 1, this type of liposome has problems such as poor stability, large particle size, zeta potential higher than -40mV, and low encapsulation efficiency and drug loading.

[0048] Figure 1 The images show the appearance of the thermosensitive liposomes prepared in Examples 1-4 and Comparative Examples 1-4 after standing at 25°C for 24 hours. Examples 1-4 all exhibited a homogeneous, semi-transparent, and stable system. Comparative Examples 1 and 2 showed a turbid state and obvious precipitation after standing for 36 hours and 42 hours, respectively. Although Comparative Examples 3 and 4 had a semi-transparent appearance, their stability was still not ideal, with precipitation occurring after 49 hours and 76 hours, respectively, indicating poor stability.

[0049] Figure 2 The figures show the cumulative release curves of the active ingredients from the liposomes prepared in Examples 1-4 at different temperatures. The results show that the liposomes in each example exhibit good thermosensitive response performance; as the temperature increases, the release rate of the active ingredients accelerates, and the cumulative release amount increases significantly. The phase transition temperatures of the liposomes in Examples 1-4 are 22℃, 39℃, 43℃, and 48℃, respectively. As can be seen from the figures, the lower the phase transition temperature, the higher the release efficiency of the liposomes at 37℃, with Example 1 showing a cumulative release rate exceeding 75% at 37℃. Given that the surface temperature of human skin is typically between 25℃ and 37℃, the thermosensitive liposomes developed in this invention have significant application potential and practical value in the field of functional cosmetics.

[0050] Figure 3 and Figure 4 The figures show the particle size distribution of liposomes prepared in Examples 1-4 and Comparative Examples 1-4, respectively. The figures show that the average particle size distribution of Examples 1-4 is less than 110 nm, indicating a narrow particle size distribution. In contrast, the average particle size distribution of Comparative Examples 1-4 is greater than 124 nm, indicating a wide particle size distribution. This suggests that the liposomes in the comparative examples have poor particle size uniformity.

[0051] In summary, this invention utilizes a binary or ternary fatty acid eutectic mixture as the thermosensitive material for liposomes. This eutectic system can fully dissolve cosmetic active molecules in the molten state. After cooling and solidification, the active ingredients are uniformly "anchored" in the fatty acid matrix in an amorphous or molecular state. Simultaneously, the active ingredients and fatty acid molecules form a stable ternary or multi-component eutectic structure through intermolecular forces such as hydrogen bonds and van der Waals forces. This fatty acid eutectic mixture exhibits a synergistic effect with phospholipids, significantly improving not only the dissolution rate of the active ingredients but also effectively enhancing the encapsulation efficiency, drug loading capacity, and long-term storage stability of the liposomes.

[0052] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A temperature-sensitive liposome, characterized in that, comprise, by mass percentage: phospholipid 5-10%, temperature-sensitive material 1-6%, polyhydric alcohol 10-15%, active ingredient 5-16%, aqueous phase 55-75%; The temperature-sensitive material is a binary or ternary eutectic mixture formed by fatty acids.

2. The thermosensitive liposome according to claim 1, characterized in that: The phospholipid is selected from one or more of the following: lecithin, hydrogenated lecithin, dicaprylphosphatidylcholine, dilaurylphosphatidylcholine, dimyristylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, 1-palmitoyl-2-ethylphosphatidylcholine, 1-palmitoyl-2-butylphosphatidylcholine, 1-palmitoyl-2- hexanoylphosphatidylcholine, 1-palmitoyl-2-octanoylphosphatidylcholine, 1-palmitoyl-2-decanoylphosphatidylcholine, 1-palmitoyl-2-lauric acid phosphatidylcholine.

3. The thermosensitive liposome according to claim 1, characterized in that: The temperature-sensitive material consists of two or three fatty acids to form a binary or ternary eutectic mixture; the fatty acids are capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, eicosanoic acid, docosanoic acid.

4. The thermosensitive liposome according to claim 1, characterized in that: The polyhydric alcohol is selected from one or more of the following: 1,4-butanediol, 1,3-propanediol, glycerol, sorbitol, polyethylene glycol, dipropylene glycol.

5. The thermosensitive liposome according to claim 1, characterized in that: The active ingredient is selected from one or more of the following: ascorbic acid, nicotinamide, ceramide, coenzyme Q10, astaxanthin, 4-butyl resorcinol, retinol, tetrahydrocurcumin.

6. The thermosensitive liposome according to claim 1, characterized in that: The liposome further comprises a preservative and / or an antioxidant; wherein the preservative is one or more of p-hydroxyacetophenone, 1,2-hexanediol, benzyl alcohol, benzoic acid, imidazole alkyl urea, and the antioxidant is one or more of tocopherol, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole.

7. The thermosensitive liposome according to any one of claims 1 to 6, characterized in that, The preparation method of the temperature-sensitive liposome comprises the following steps: (1) mixing and heating the phospholipid, temperature-sensitive material, polyhydric alcohol, active ingredient, preservative, and antioxidant to obtain solution A; (2) mixing solution A and the aqueous phase under constant temperature conditions and performing homogenization treatment; (3) performing ultrasonic treatment on the mixture obtained in step (2) to make the active ingredient stably embedded and uniformly dispersed in the fatty acid through intermolecular interaction to form an active molecule-fatty acid ternary or multi-component eutectic system, and the eutectic system cooperates with the phospholipid to finally obtain the temperature-sensitive liposome.

8. The thermosensitive liposome according to claim 7, characterized in that: The heating temperature in step (1) is 80-90°C; The constant temperature condition in step (2) is 85-95°C, the rotation speed of homogenization is 10,000-15,000 rpm, and the homogenization time is 10-15 min.

9. The thermosensitive liposome according to claim 7, characterized in that: The ultrasonic treatment in step (3) uses a probe ultrasonic instrument, the ultrasonic power is 450-500 W, the ultrasonic temperature is 10-15°C, and the ultrasonic time is 10-20 min.

10. The temperature-sensitive liposome according to any one of claims 1-9 for use in cosmetics.

Images