Cosmetic liposome and preparation method and application thereof

Abstract

The application discloses liposomes for cosmetics, a preparation method and application thereof. The liposomes contain hydrogenated lecithin, sterol compounds, liquid oil and a stabilizer. The liposomes have high stability, can maintain good stability under the condition of long-time placement at low temperature and high temperature, can overcome the stimulation and bad skin feeling caused by the combination of high-osmotic-pressure liposomes and the corresponding isotonic external phase in application, can significantly enhance the related activity of effective substances, and have great development and application potential in the field of cosmetic application.

Description

Technical Field

[0001] This invention belongs to the field of cosmetics, specifically relating to a cosmetic liposome, its preparation method, and its application. Background Technology

[0002] Liposomes are microscopic spherical carriers that encapsulate active ingredients within a lipid bilayer. As a delivery medium for active ingredients in pharmaceuticals and cosmetics, liposome formulations offer numerous advantages on the skin, such as long-lasting release, protection of active ingredients, enhanced penetration, and skin nourishment.

[0003] Liposome technology requires significant use of organic solvents in its initial manufacturing process. However, in the cosmetics industry, liposomes are often formed using high concentrations of polyols or surfactants. This approach introduces other challenges, such as concerns about the safety of surfactants and the osmotic pressure challenges posed by high concentrations of polyols for product application. Therefore, liposome design must consider not only its own stability but also its osmotic pressure requirements.

[0004] The influence of the internal and external osmotic pressure difference. In cosmetic applications, the design of high osmotic pressure formulations is undoubtedly very difficult. High osmotic pressure formulations require the addition of high concentrations of low molecular weight substances, such as glycerin, butylene glycol, and similar small molecule substances. The use of such high concentrations will inevitably encroach on the space of other functional substances, while bringing irritation and unpleasant skin feel, thus negatively affecting the regulation of efficacy and skin feel.

[0005] To address the aforementioned technical problems in related technologies, there is a need for a liposome that does not require the addition of surfactants, can overcome the effects of high osmotic pressure, and possesses high stability. This would solve problems in related technologies such as skin cell dehydration or damage caused by the high osmotic pressure of liposomes, decreased safety due to the addition of surfactants, and low stability. Summary of the Invention

[0006] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the present invention proposes a cosmetic liposome, its preparation method, and its application. The liposome does not require the addition of surfactants, exhibits good stability, does not show significant changes in particle size during long-term storage, and can significantly enhance the relevant activity of active ingredients.

[0007] In a first aspect, the present invention provides a liposome, wherein, by weight percentage, the liposome contains 3-15% hydrogenated lecithin, 0.3-3% sterol compounds, 0.2-1.5% liquid oil, and 10-30% stabilizer, wherein:

[0008] The sterol compound is selected from at least one of cholesterol and phytosterol;

[0009] The liquid oil is selected from at least one of dibutyl diacidate (CAS No.: 105-99-7), caprylic / capric triglyceride (GTCC, CAS No.: 65381-09-1), coconut oil alcohol-caprylic / capric ester (CAS No.: 95912-86-0), and diisostearyl malate (CAS No.: 67763-18-2);

[0010] The stabilizer is selected from at least one of polyols and sugar compounds.

[0011] In some embodiments of the present invention, the hydrogenated lecithin contains ≥60% phosphatidylcholine (PC) and has an iodine value ≤10.

[0012] In this invention, since hydrogenated lecithin is a mixture, even if they are from the same source, the content of different types of phospholipids will fluctuate between batches. If the purity of lecithin is not properly addressed, it is difficult to ensure the stability of product quality. The higher the content of phosphatidylcholine, the more stable the product quality. Since hydrogenated lecithin contains a large amount of polyunsaturated fatty acids, it is easily oxidized by oxygen and light in the air. Therefore, it is necessary to control the iodine value in hydrogenated lecithin.

[0013] In some embodiments of the present invention, the phytosterol is any one of 4-amethylsterol, 4-methylsterol, and 4,4-dimethylsterol.

[0014] In some embodiments of the present invention, the total sterol content of the selected cholesterol and phytosterols is ≥95%.

[0015] In some specific embodiments of the present invention, the sterol compound is cholesterol.

[0016] In some specific embodiments of the present invention, the liquid oil is dibutyl adipate.

[0017] In some embodiments of the present invention, the polyol is selected from at least one of glycerol and 1,3-butanediol.

[0018] In some specific embodiments of the present invention, the polyol is glycerol.

[0019] In some embodiments of the present invention, the carbohydrate compound is selected from at least one of trehalose, mannitol, xylitol, sucrose, erythritol, sorbitol, glucose, and rhamnose.

[0020] In some specific embodiments of the present invention, the carbohydrate compound is trehalose.

[0021] In some embodiments of the present invention, the liposomes further contain, by weight percentage, and / or solvents; the pH adjuster and / or solvents account for 60-80% of the total mass of the composition.

[0022] In some embodiments of the present invention, the pH adjuster is selected from at least one of arginine, citric acid, sodium citrate, triethanolamine, sodium hydroxide, potassium hydroxide, hydrochloric acid, phosphate, and hydroxyethylpiperazine ethanesulfonic acid.

[0023] In some specific embodiments of the present invention, the pH adjuster is arginine.

[0024] In some embodiments of the present invention, the solvent is water.

[0025] In some embodiments of the present invention, the osmotic pressure of the liposomes is 2000-4000 mosm / kg.

[0026] In this invention, the osmotic pressure of the liposomes can be adjusted by controlling the amount of stabilizer added.

[0027] A second aspect of the present invention provides a method for preparing the liposomes described in the first aspect of the present invention, comprising the following steps: mixing a sterol compound and a liquid oil and heating them, then adding hydrogenated lecithin, a stabilizer, a pH adjuster and deionized water, mixing, homogenizing, sonicating and cooling to obtain the liposomes.

[0028] In some embodiments of the present invention, the heating temperature is 80–100°C.

[0029] In some embodiments of the present invention, the homogenization rotation speed is 5000-10000 rpm and the time is 2-10 min.

[0030] In some embodiments of the present invention, the ultrasonic power of the ultrasonic treatment is 30-50% of the maximum power of the ultrasonic instrument, and the ultrasonic treatment time is 1-5 minutes; wherein the maximum power of the ultrasonic instrument used is 550W.

[0031] In some embodiments of the present invention, the cooling is a natural cooling to 23-27°C.

[0032] In some embodiments of the present invention, the pH value after the addition of the pH adjuster is 6 to 7.

[0033] A third aspect of the present invention provides the use of the liposomes described in the first aspect of the present invention in the preparation of cosmetics.

[0034] A fourth aspect of the present invention provides a composition comprising the liposomes described in the first aspect of the present invention.

[0035] In some embodiments of the present invention, the composition further contains at least one functional active ingredient, which accounts for 0.2 to 15% of the total mass of the composition.

[0036] In some embodiments of the present invention, the functional active ingredient is selected from at least one of water-soluble active ingredients and fat-soluble active ingredients.

[0037] In some embodiments of the present invention, the functional active ingredient is a cosmetic raw material with whitening, moisturizing, repairing, or wrinkle-reducing and firming effects.

[0038] In some specific embodiments of the present invention, the functional active ingredient is SYNCHROLIFE MBAL, which contains: glycerol, 1,2-pentanediol, rosemary leaf extract, lactic acid, palmitoyl tetrapeptide-7, and 5,7-dihydroxyflavone; purchased from Croda Chemicals (Shanghai) Co., Ltd.

[0039] In some embodiments of the present invention, the composition further contains excipients acceptable for cosmetic formulations.

[0040] In some embodiments of the present invention, the dosage form of the composition includes serum, lotion, face mask, skin cream, and skin lotion.

[0041] A fifth aspect of the present invention provides a method for preparing the composition described in the fourth aspect of the present invention, comprising the following steps: mixing liposomes with a functional active ingredient to obtain the composition.

[0042] In some embodiments of the present invention, the composition further contains excipients acceptable for cosmetic formulations.

[0043] In some embodiments of the present invention, the excipients include, but are not limited to, pH adjusters, thickeners, and humectants.

[0044] In some embodiments of the present invention, the composition contains, by weight percentage, 5-15% liposomes as described in the first aspect of the present invention, 0.01-0.1% pH adjuster, 0.1-1% thickener, 10-40% humectant, and the balance being deionized water.

[0045] In some embodiments of the present invention, the thickener is carbomer.

[0046] In some embodiments of the present invention, the humectant includes, but is not limited to, 1,3-propanediol, glycerin, maltitol, 1,3-butanediol, polyethylene glycol-32, and erythritol.

[0047] The beneficial effects of this invention are:

[0048] 1. By controlling the osmotic pressure during the liposome preparation process, the liposomes prepared in this invention have the characteristics of high stability and can maintain good stability under long-term storage at low and high temperatures.

[0049] 2. The liposomes prepared by this invention take into account both their own stability and the influence of internal and external phases in actual formulation applications. A suitable osmotic pressure formulation for cosmetic design can be designed, which can overcome the irritation and unpleasant skin feel caused by the combination of high osmotic pressure liposomes and corresponding isotonic external phases during application, thereby negatively affecting the regulation of skin feel and efficacy. It has great application value in cosmetic applications.

[0050] 3. When the liposomes prepared by this invention are combined with the active ingredient to form a composition, the relevant activity of the active ingredient can be significantly enhanced, and it has great potential for development and application in the field of cosmetics. Attached Figure Description

[0051] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein:

[0052] Figure 1 The particle size of Example 3 of the present invention after being mixed with different solutions under different treatment conditions;

[0053] Figure 2 This refers to the particle size of Comparative Example 3 of the present invention after being mixed with different solutions under different treatment conditions;

[0054] Figure 3 The standard curve shows the inhibition rate of water-soluble vitamin E in ABTS free radical solution.

[0055] Figure 4 This is a comparison graph showing the effect of the composition of Example 4 of the present invention on scavenging ABYS free radicals with other test groups, where "*" indicates a significant difference compared with the blank control group (p<0.05). Detailed Implementation

[0056] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0057] The room temperature mentioned in the following examples is 23-27°C.

[0058] Unless otherwise specified, all experimental materials and reagents used are commercially available consumables and reagents.

[0059] Example 1

[0060] In this embodiment, a liposome was prepared from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, trehalose, deionized water, and arginine.

[0061] Its preparation method is as follows:

[0062] (1) Mix the A phase components evenly and heat to 90°C;

[0063] (2) At 85℃, add phase B component and homogenize at 7500 rpm for 6 min;

[0064] (3) After homogenization, ultrasonic treatment with 40% of the ultrasonic power, i.e. 220W, for 3 minutes is performed. The mixture is then stirred evenly and cooled to room temperature to obtain the final product.

[0065] The content of each component of the liposome in this embodiment is shown in Table 1.

[0066] Example 2

[0067] In this embodiment, a liposome was prepared from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, deionized water, and arginine.

[0068] Its preparation method is the same as that in Example 1 above.

[0069] The content of each component of the liposome in this embodiment is shown in Table 1.

[0070] Example 3

[0071] In this embodiment, a liposome was prepared from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, deionized water, and arginine.

[0072] Its preparation method is the same as that in Example 1 above.

[0073] The content of each component of the liposome in this embodiment is shown in Table 2.

[0074] Example 4

[0075] This embodiment prepared a composition containing SYNCHROLIFE MBAL (containing: glycerol, 1,2-pentanediol, rosemary leaf extract, lactic acid, palmitoyl tetrapeptide-7, 5,7-dihydroxyflavone) purchased from Croda Chemicals (Shanghai) Co., Ltd., which was prepared from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, deionized water, SYNCHROLIFE MBAL and arginine.

[0076] Its preparation method is as follows:

[0077] (1) Mix the A phase components evenly and heat to 90°C;

[0078] (2) At 85℃, add phase B component and homogenize at 7500 rpm for 6 min;

[0079] (3) After homogenization, ultrasonic treatment with 40% of the ultrasonic power, i.e. 220W, for 3 minutes was carried out, and the mixture was stirred evenly and then cooled to 45℃.

[0080] (4) Add the C phase component at 45℃, stir evenly, and cool to room temperature to obtain the final product.

[0081] The content of each component of the liposome in this embodiment is shown in Table 3.

[0082] Example 5

[0083] This embodiment prepared an essence containing liposomes from Example 2, which was prepared from the following components: carbomer, 1,3-propanediol, glycerol, maltitol, 1,3-butanediol, polyethylene glycol-32, erythritol, the liposomes prepared in Example 2 above, arginine, and deionized water.

[0084] Its preparation method is as follows:

[0085] (1) Mix phase A components evenly and heat to 85°C until the system is homogeneous;

[0086] (2) After mixing evenly, lower the temperature to room temperature, add phase B component, stir evenly, and the product is obtained.

[0087] The content of each component of the essence in this embodiment is shown in Table 4.

[0088] Comparative Example 1

[0089] This comparative example prepared a liposome from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, mannitol, deionized water, and arginine.

[0090] Its preparation method is the same as that in Example 1 above.

[0091] The content of each component of the liposome in this embodiment is shown in Table 1.

[0092] Comparative Example 2

[0093] A liposome was prepared in this comparative example from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, trehalose, deionized water, and arginine.

[0094] The preparation method is the same as in Example 1 above.

[0095] The content of each component of the liposome in this embodiment is shown in Table 1.

[0096] Comparative Example 3

[0097] This comparative example prepared a liposome from the following components: cholesterol, dibutyl adipate, hydrogenated lecithin, glycerol, deionized water, and arginine.

[0098] Its preparation method is the same as in Example 1 above;

[0099] The content of each component of the liposome in this embodiment is shown in Table 2.

[0100] Table 1. Mass percentage ratio of different liposomes

[0101]

[0102]

[0103] Table 2. Mass percentage ratio of liposomes with different osmotic pressures

[0104]

[0105] Table 3. Mass percentage ratio of the composition in Example 4

[0106]

[0107] Table 4. Mass percentage ratio of the essence in Example 5

[0108]

[0109]

[0110] Effect verification test experiment

[0111] 1. Osmotic pressure and stability testing

[0112] Immediately after obtaining Examples 1-2 and Comparative Examples 1-2, the osmotic pressure, particle size, and distribution coefficient (PI) were measured. Then, after being placed at -18℃ and 48℃ for 1 month, the average particle size and distribution coefficient of Examples 1-2 and Comparative Examples 1-2 were measured. The particle size tester was Zetasizer Lab, and the osmotic pressure tester was YASN Osmo310. The test methods were the conventional test methods of the respective instruments. The test results are shown in Table 5.

[0113] Table 5. Results of osmotic pressure and stability tests for different liposomes

[0114]

[0115]

[0116] As can be seen from the data of Examples 1-2 and Comparative Examples 1-2 above, in Comparative Examples 1-2 with an osmotic pressure below 2000 mosm / kg, the liposomes showed poor stability under low-temperature storage conditions, and precipitates were produced. Furthermore, in Comparative Example 1, the liposome particle size increased and the dispersion coefficient deteriorated under high-temperature storage conditions, and the overall appearance became milky white. In contrast, Examples 1-2 with an osmotic pressure above 2000 mosm / kg were able to maintain good stability under both low-temperature and high-temperature storage conditions, with minimal particle size changes and a stable dispersion coefficient.

[0117] 2. Test of particle size of liposomes with different osmotic pressures in solutions with different osmotic pressures.

[0118] In cosmetic manufacturing, liposomes exist as a core ingredient in the formulation. The formulation medium in which liposomes exist is the relative external phase of the liposomes. The osmotic pressure of the relative external phase also affects the stability of the liposomes. This test verifies the influence of the osmotic pressure of the relative external phase through two liposomes with different osmotic pressures, Example 3 and Comparative Example 3.

[0119] The sample from Example 3 was taken and placed in different solutions according to the mass ratio of liposome sample to solution = 1:9. The solutions used as the relative external phase were pure water, 10% glycerol solution, 20% glycerol solution, 40% glycerol solution, and pure glycerol. The samples were tested under three conditions: room temperature, accelerated high temperature at 45°C for 3 days, and accelerated high temperature at 45°C for 7 days. The particle size of the liposomes was determined by referring to the particle size test method in the above osmotic pressure and stability test.

[0120] Take the sample from Comparative Example 3 and place it in different solutions according to the mass ratio of liposome sample:solution = 1:9. The solutions used as the relative external phase are pure water, 10% glycerol solution, 40% glycerol solution, 60% glycerol solution, and pure glycerol. The samples are tested immediately at room temperature. Then, the samples are tested under three conditions: accelerated high temperature at 45°C for 3 days and accelerated high temperature at 45°C for 7 days. The particle size of the liposomes is determined by referring to the particle size test method in the above osmotic pressure and stability test.

[0121] In Example 3 and Comparative Example 3, the measured osmotic pressures were 2300 mosm / kg and 6500 mosm / kg, respectively. The external phases for both osmotic pressure measurements can be considered as 20% glycerol and 40% glycerol solutions, respectively. The test results are as follows: Figure 1 and Figure 2 As shown.

[0122] from Figure 1 and Figure 2 The results show that when liposomes are in a low-osmotic-pressure solution, such as pure water, the particle size tends to increase, and this tendency increases further with increasing temperature. Conversely, when liposomes are in a high-osmotic-pressure solution, such as pure glycerol, the particle size decreases drastically, and this tendency decreases slightly further with increasing temperature. Meanwhile, the particle size change of liposomes is minimal in isotonic solutions. This indicates that when liposomes are in relative external phases with different osmotic pressures, the greater the osmotic pressure difference, the greater the particle size change.

[0123] Therefore, the design of liposomes should consider not only their own stability but also the influence of the osmotic pressure difference between the internal and external phases during application. In cosmetic applications, designing high-osmotic-pressure formulations is undoubtedly very difficult because such formulations require the addition of high concentrations of low-molecular-weight substances, such as glycerol and butylene glycol. The high concentration of these substances will inevitably encroach on the space of other functional ingredients, leading to irritation and unpleasant skin feel, such as stickiness during use, thus negatively impacting efficacy and skin feel. Therefore, the liposomes prepared in this invention's embodiments balance their own stability with considerations of the internal and external phases in actual formulation applications, making them applicable to practical formulation design and production, and possessing significant industrial value.

[0124] 3. Test on the scavenging effect of liposomes carrying active ingredients on ABYS free radicals

[0125] By designing a liposome carrying the SYNCHROLIFEMBAL product purchased from Croda Chemicals (Shanghai) Co., Ltd., namely the composition prepared in Example 4 above, the effect of carrying the active ingredient in the liposome was tested, specifically the ABTS free radical scavenging ability of the liposome was tested.

[0126] Blank control (BC): Deionized water;

[0127] Test Sample 1: A 2% aqueous solution of SYNCHROLIFE MBAL;

[0128] Test Sample 2: An aqueous solution of the Example 4 sample with a mass fraction of 10%;

[0129] Test Sample 3: An aqueous solution containing the composition of each component in the sample of Example 4, wherein each component was not lipid-treated, and the composition had a mass fraction of 10% in the aqueous solution;

[0130] Standard product: Water-soluble vitamin E (Trolox).

[0131] Experimental Principle: 2,2-Aza-bis(3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt (ABTS, CAS No.: 30931-67-0) reacts with potassium persulfate to generate a green ABTS free radical solution. This free radical has a maximum absorbance at 734 nm. This test uses the Swiss TECAN brand multi-functional full-band continuous spectrometer INFINITE E PLEX and its corresponding detection method to measure the absorbance at 734 nm, thus determining its concentration.

[0132] ABTS free radical scavenging method: If the absorbance at 734 nm decreases after a substance is added to an ABTS free radical solution, it indicates that the substance has free radical scavenging activity and is an antioxidant.

[0133] Using Trolox as a standard, a standard curve was plotted, such as... Figure 3 As shown, the linear equation of Trolox's ABTS standard curve is y = 0.4627x + 0.1504, R0 2 =0.9990, Trolox's IC 50 The value was 107.76 ± 7.57 μg / mL. (For example...) Figure 4As shown, although both samples have the ability to scavenge ABTS free radicals, it can be seen that there is a significant difference in their scavenging abilities. The aqueous solution of the 10% (w / w) sample of Example 4 has a significantly higher ABTS free radical scavenging ability than the aqueous solution of the 2% (w / w) SYNCHROLIFE MBAL and the aqueous solution of the composition containing the components of the Example 4 sample without liposome treatment. This indicates that the ABTS free radical scavenging ability of the active ingredient of SYNCHROLIFE MBAL is significantly improved after incorporating the liposomes of the present invention.

[0134] 4. Stability test of the essence containing liposomes from the embodiments of the present invention

[0135] By testing the stability of the serum containing the liposomes of Example 2, i.e. the serum prepared in Example 5, this example verifies the stability effect of the liposomes in cosmetics: the average particle size and distribution coefficient of the serum prepared in Example 5 were tested immediately after preparation and after being placed at room temperature, -18°C and 48°C for 3 months. The test method is the same as the above osmotic pressure and stability test. The results are shown in Table 6.

[0136] Table 6. Stability test results of the serum in Example 5.

[0137]

[0138]

[0139] As shown in Table 6, the liposomes prepared in the embodiments of the present invention have good stability in the essence, and the particle size does not change significantly.

[0140] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made within the scope of knowledge possessed by those skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof can be combined with each other unless otherwise specified.

Claims

1. A liposome, characterized in that, By weight percentage, the liposomes contain 3-15% hydrogenated lecithin, 0.3-3% sterols, 0.2-1.5% liquid oil, and 10-30% stabilizer. The sterols are selected from at least one of cholesterol and phytosterols; the liquid oil is selected from dibutyl bis(2-ethylhexanoate), caprylic / capric triglyceride, and coconut oil alcohol. The liposome contains at least one of caprylate / decanoate and diisostearyl malate; the stabilizer is selected from at least one of polyols and sugar compounds; the hydrogenated lecithin contains ≥60% phosphatidylcholine and has an iodine value ≤10; the liposome also contains a pH adjuster and a solvent; the osmotic pressure of the liposome is 2000–4000 mosm / kg; the pH value after the addition of the pH adjuster is 6–7.

2. The liposomes according to claim 1, characterized in that, The pH adjuster and / or solvent account for 60-80% of the total mass of the composition by weight percentage.

3. The method for preparing liposomes according to any one of claims 1 to 2, characterized in that, The process includes the following steps: mixing sterol compounds and liquid oils and heating them, then adding hydrogenated lecithin, stabilizers, pH adjusters and deionized water, mixing, homogenizing, sonicating and cooling to obtain the liposomes.

4. The use of the liposomes according to any one of claims 1 to 2 in the preparation of cosmetics.

5. A composition, characterized in that, The composition contains the liposomes according to any one of claims 1 to 2.

6. The composition according to claim 5, characterized in that, The composition further contains at least one functional active ingredient, which accounts for 0.2% to 15% of the total mass of the composition.

7. The composition according to claim 5, characterized in that, The composition also contains excipients acceptable for cosmetic formulations.

8. The composition according to any one of claims 5 to 7, characterized in that, The composition dosage forms include serums, toners, face masks, skin creams, and skin lotions.

9. A method for preparing the composition according to any one of claims 5 to 8, characterized in that, Includes the following steps: The liposomes are mixed with the functional active ingredients to obtain the product.

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