4-butylresorcinol liposome as well as preparation method and application thereof

Abstract

The invention provides a preparation method and application of 4-butylresorcinol liposome, and belongs to the technical field of cosmetic raw material preparation. The 4-butylresorcinol liposome is prepared from the following components in percentage by weight: 5 to 15 percent of caprylic / capric triglyceride, 2 to 8 percent of hydrogenated lecithin, 0.1 to 3 percent of cholesterol, 1 to 10 percent of 4-butylresorcinol, 0.5 to 3 percent of emulsifier, 0.003 to 0.1 percent of pH (Potential of Hydrogen) regulator, 0.01 to 0.5 percent of metal ion chelating agent, 0.1 to 5 percent of antioxidant and 55 to 90 percent of solvent. The solubility, skin irritation and permeability of 4-butylresorcinol are improved by compounding hydrogenated lecithin, cholesterol and the emulsifier, and the problem that 4-butylresorcinol liposome is prone to being oxidized and discolored is solved through an antioxidant system composed of the pH regulator, the metal ion chelating agent and the compound antioxidant.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetic raw material preparation, and particularly relates to a preparation method of 4-butylresorcinol liposome and application thereof. Background Art

[0002] 4-Butylresorcinol is an excellent tyrosinase inhibitor with a strong whitening effect, but it is difficult to dissolve in water, has a high skin irritation and poor permeability. In addition, because the phenolic hydroxyl group in the molecular structure of resorcinol has a strong reducing property, it is easily oxidized into quinone-type colored substances, which makes the system turn yellow, reddish brown or even dark brown after adding it to the product, which limits its application in cosmetics.

[0003] As a resorcinol derivative, its structural formula is:

[0004]

[0005] Liposome technology can solve the problems of poor stability, easy discoloration and poor absorption of effective ingredients in cosmetics. Liposomes are nano-spherical vesicles composed of phospholipid bilayers, which can encapsulate water-soluble and fat-soluble drugs or active ingredients, thereby improving their stability and skin absorption. Liposomes are similar to the lipids in the stratum corneum of the skin and can enter the skin through the permeation of the stratum corneum cell membrane, skin hair follicles or the intercellular space of the stratum corneum, while providing space for the storage of active ingredients in the skin, increasing local accumulation and achieving long-term sustained release.

[0006] At present, there are many reports on solving the practical application problems of 4-butylresorcinol in cosmetics. For example, patent CN117797040A discloses a whitening nanoemulsion containing 4-butylresorcinol and a preparation method thereof, aiming to provide a whitening nanoemulsion that inhibits melanin synthesis and accelerates the metabolic degradation of melanin; its technical scheme includes the following components in mass fraction: active factor 13.08%-29.12%, emulsifier phase 4%-40.5%, organic phase 2.2%-41.8%, preservative 0.1%-1%, and water in appropriate amount; the active factor includes 4-butylresorcinol, nonapeptide-1, decarboxylated carnosine hydrochloride, 3-o-ethyl ascorbic acid, and tocopherol acetate; the emulsifier includes poloxamer, polyvinylpyrrolidone, and cetearyl alcohol polyether-20; however, the scheme does not involve liposome preparation, and does not involve research on color stability and transdermal performance.

[0007] Another example is Chinese patent CN115836979A, which discloses a 4-butylresorcinol liposome and a preparation method thereof. The ingredients are calculated by weight percentage: 4-butylresorcinol 0.01%-10%; antioxidant 0.1%-5%; phospholipid 1%-5%; solvent 5%-85%; preservative 1%-3%; the rest is deionized water, wherein the phospholipid is selected from one or more of soybean lecithin, hydrogenated lecithin, and sunflower seed lecithin; it has good stability, is not easy to be oxidized and discolored, has good permeability through the skin, has a better whitening effect and other beneficial effects, but the particle size of the liposome is relatively large (140-162nm), and the larger particle size is not conducive to transdermal absorption. At the same time, studies have shown that the introduction of emulsifiers changes the flexibility of liposomes and further improves the transdermal absorption performance. Therefore, it can be seen that this scheme needs to be further optimized.

[0008] For another example, Chinese patent CN114588054A discloses a whitening and moisturizing composition and its preparation method and application, which includes the following components by weight: 1-5 parts of schizophyllan polysaccharide, 1-5 parts of dextran, 10-25 parts of modified lecithin, 1-5 parts of cholesterol, 2-4 parts of arbutin, 1-5 parts of phenethyl resorcinol, 5-10 parts of tetrahydrocurcumin, and 40-70 parts of water. The invention uses arbutin and phenethyl resorcinol as the main whitening ingredients to inhibit the activity of tyrosinase and reduce the production of melanin; the modification of lecithin improves stability and hydrophilicity, and the combination of modified lecithin and cholesterol forms liposomes, which encapsulate arbutin and phenethyl resorcinol and improve their transdermal absorption performance; schizophyllan polysaccharide and dextran are added at the same time to improve moisturizing, whitening and antioxidant properties. The synergistic effect between the components makes the product have excellent whitening and moisturizing effects, high stability and strong permeability. However, this patent does not involve the design of liposome color stability, and the patented formula needs to be further improved.

[0009] Therefore, it is necessary to develop a preparation method of 4-butylresorcinol liposomes with high liposome encapsulation rate, good permeability, low irritation, high stability and not easy to be oxidized and discolored. Summary of the invention

[0010] Based on the deficiencies in the prior art, the present invention aims to provide a 4-butylresorcinol liposome and a preparation method thereof. The present invention improves the solubility, skin irritation and permeability of 4-butylresorcinol by compounding hydrogenated lecithin, cholesterol and an emulsifier. Compared with a nanoemulsion prepared with an emulsifier alone, the skin affinity is better after adding hydrogenated lecithin. Compared with a liposome prepared with only hydrogenated lecithin, the compounding of cholesterol and an emulsifier can improve the encapsulation rate and skin permeability of the liposome.

[0011] The problem of 4-butylresorcinol liposome being easily oxidized and discolored is further improved by adding a pH regulator, a metal ion chelator and a compound antioxidant to form an antioxidant system. The antioxidant system has the characteristics of a weakly acidic pH of the system, which is helpful for stabilizing the polyphenol weak acid system; the compound antioxidant is a combination of oil-soluble and water-soluble antioxidants, which are respectively used to combat the oxidative discoloration of free unencapsulated 4-butylresorcinol in water and encapsulated 4-butylresorcinol in the oil phase; the metal ion chelator is used to chelate transition metal ions in the system to inhibit the catalytic oxidation reaction caused by them.

[0012] Based on the above purpose, the present invention adopts the following technical solutions to achieve:

[0013] In one aspect, the present invention provides a 4-butylresorcinol liposome comprising the following components by weight percentage:

[0014] Caprylic / capric triglyceride 5-15%, hydrogenated lecithin 2-8%, cholesterol 0.1-3%, 4-butylresorcinol 1-10%, emulsifier 0.5-3%, pH adjuster 0.003-0.1%, metal ion chelator 0.01-0.5%, antioxidant 0.1-5% and solvent 55-90%.

[0015] Preferably, the 4-butylresorcinol liposome comprises the following components by weight percentage:

[0016] Caprylic / capric triglyceride 8-12%, hydrogenated lecithin 4-6%, cholesterol 1-1.5%, 4-butylresorcinol 3-6%, emulsifier 1-2%, pH adjuster 0.003-0.006%, metal ion chelator 0.05-0.1%, antioxidant 0.3-1.5% and solvent 70-80%.

[0017] Further preferably, the 4-butylresorcinol liposome comprises the following components by weight percentage:

[0018] Caprylic / capric triglyceride 12%, hydrogenated lecithin 4%, cholesterol 1.5%, 4-butylresorcinol 5%, emulsifier 1%, pH adjuster 0.006%, metal ion chelator 0.1%, antioxidant 1.005% and solvent 75.389%.

[0019] in,

[0020] The emulsifier is selected from one or more of polyglycerol emulsifiers or sorbitol emulsifiers;

[0021] Preferably, the emulsifier is selected from one or more of polyglycerol-10-myristic acid ester, polyglycerol-10-laurate, polyglycerol-10-stearate, sorbitan sesquioleate and sorbitan stearate;

[0022] Preferably, the emulsifier is selected from polyglycerol-10-myristate.

[0023] The pH regulator is citric acid.

[0024] The metal ion chelating agent is selected from one or more of disodium EDTA, disodium edetate, and etidronic acid;

[0025] The antioxidant is selected from oil-soluble antioxidants and / or water-soluble antioxidants;

[0026] Preferably, the antioxidant is a combination of an oil-soluble antioxidant and a water-soluble antioxidant;

[0027] The oil-soluble antioxidant is selected from one or more of vitamin E, VE acetate, butylated hydroxyanisole, butylated hydroxytoluene, tert-butylhydroquinone, tert-butylhydroquinone, hydroxymethoxyphenyl decanone, carnosic acid, guaiacol, and propyl gallate;

[0028] The water-soluble antioxidant is selected from one or more of sodium pyrosulfite, sodium bisulfite, sodium phytate, ergothioneine, ascorbic acid, isoascorbic acid and salts thereof.

[0029] Preferably, the oil-soluble antioxidant is selected from one or more of VE acetate, butylated hydroxytoluene, and hydroxymethoxyphenyl decanone;

[0030] The water-soluble antioxidant is selected from one or more of sodium pyrosulfite, ergothioneine and sodium isoascorbate.

[0031] Further preferably, the antioxidant is a mixture of hydroxymethoxyphenyldecanone and sodium isoascorbate, and the mass ratio of the two is 0.001-0.01:1; preferably 0.005:1.

[0032] The solvent is a mixed solution of water and glycerol, and the mass ratio of glycerol to water is 0.05-1:1, preferably 0.25:1.

[0033] On the other hand, the present invention also provides a method for preparing the above-mentioned 4-butylresorcinol liposome, comprising the following steps:

[0034] (1) preparing an aqueous phase: mixing water, glycerol, a water-soluble antioxidant, a pH adjuster and a chelating agent to obtain an aqueous phase;

[0035] (2) weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, emulsifier, oil-soluble antioxidant and 4-butylresorcinol, mixing them and stirring them in a water bath until they are completely dissolved to obtain an oil phase;

[0036] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then treated with a high-pressure homogenizer to obtain 4-butylresorcinol liposomes.

[0037] The pressure of the high-pressure homogenization is 600 bar, and the number of homogenization times is 8 times.

[0038] The present invention also provides application of the 4-butylresorcinol liposome in preparing cosmetics.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] (1) The present invention improves the solubility, skin irritation and permeability of 4-butylresorcinol by compounding hydrogenated lecithin, cholesterol and an emulsifier. Compared with the nanoemulsion prepared by a single emulsifier, the skin affinity is better after adding hydrogenated lecithin. Compared with the liposome prepared by hydrogenated lecithin alone, the compounding of cholesterol and an emulsifier can improve the encapsulation rate and skin permeability of the liposome.

[0041] (2) The present invention improves the problem of 4-butylresorcinol liposome being easily oxidized and discolored by adding a pH regulator, a metal ion chelating agent and a compound antioxidant to form an antioxidant system. The present invention is characterized in that the pH of the system is weakly acidic, which is conducive to the stability of the polyphenol weak acid system; the compound antioxidant is a combination of oil-soluble and water-soluble antioxidants, which are respectively used to combat the oxidative discoloration of free unencapsulated 4-butylresorcinol in water and encapsulated in the oil phase; the metal ion chelating agent is used to chelate the transition metal ions in the system to inhibit the catalytic oxidation reaction caused by them. DETAILED DESCRIPTION

[0042] The following will be combined with the tables in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0043] Hereinafter, examples and comparative examples of the present invention will be shown to explain the composition of the present invention in more detail, but the present invention is not limited thereto.

[0044] Example 1 A 4-butylresorcinol liposome and its preparation method

[0045] The composition includes the following components by weight percentage:

[0046] Caprylic / capric triglyceride 6 g, hydrogenated lecithin 4 g, cholesterol 0.25 g, 4-butylresorcinol 5 g, emulsifier 1 g, pH adjuster 0.1 g, metal ion chelator 0.05 g, antioxidant 0.3 g and solvent 83.3 g.

[0047] The emulsifier is sorbitan sesquioleate.

[0048] The pH regulator is citric acid.

[0049] The metal ion chelating agent is disodium EDTA.

[0050] The antioxidant is a mixture of butylated hydroxytoluene and sodium metabisulfite, and the mass ratio of the two is 2:1.

[0051] The solvent is a mixture of glycerol and water, and the mass ratio of the two is 0.25:1.

[0052] The preparation method comprises the following steps:

[0053] (1) preparing an aqueous phase: mixing water, glycerol, sodium metabisulfite, disodium TDTA, and citric acid to obtain an aqueous phase;

[0054] (2) Weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, butylated hydroxytoluene, sorbitan sesquioleate and 4-butylresorcinol, mixing them and stirring in a water bath until they are completely dissolved to obtain an oil phase;

[0055] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then homogenized 8 times at 600 bar to obtain 4-butylresorcinol liposomes.

[0056] Example 2 A 4-butylresorcinol liposome and its preparation method

[0057] The composition includes the following components by weight percentage:

[0058] Caprylic / capric triglyceride 14 g, hydrogenated lecithin 4 g, cholesterol 1 g, 4-butylresorcinol 6 g, emulsifier 1 g, pH adjuster 0.006 g, metal ion chelator 0.1 g, antioxidant 1.5 g and solvent 72.394 g.

[0059] The emulsifier is polyglycerol-10-laurate.

[0060] The pH regulator is citric acid.

[0061] The metal ion chelating agent is disodium edetate.

[0062] The antioxidant is a mixture of VE acetate and sodium phytate, and the mass ratio of the two is 2:1.

[0063] The solvent is a mixture of glycerol and water, and the mass ratio of the two is 0.25:1.

[0064] The preparation method comprises the following steps:

[0065] (1) preparing an aqueous phase: mixing water, glycerin, sodium phytate, disodium edetate, and citric acid to obtain an aqueous phase;

[0066] (2) Weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, VE acetate, polyglycerol-10-laurate and 4-butylresorcinol, mixing them and stirring them in a water bath until they are completely dissolved to obtain an oil phase;

[0067] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then homogenized 8 times at 600 bar to obtain 4-butylresorcinol liposomes.

[0068] Example 3 A 4-butylresorcinol liposome and its preparation method

[0069] The composition includes the following components by weight percentage:

[0070] Caprylic / capric triglyceride 10 g, hydrogenated lecithin 2.5 g, cholesterol 2.5 g, 4-butylresorcinol 1 g, emulsifier 1 g, pH adjuster 0.006 g, metal ion chelator 0.2 g, antioxidant 1.05 g and solvent 81.744 g.

[0071] The emulsifier is sorbitan stearate.

[0072] The pH regulator is citric acid.

[0073] The metal ion chelating agent is disodium EDTA.

[0074] The antioxidant is a mixture of VE acetate and ergothioneine, and the mass ratio of the two is 1:0.05.

[0075] The solvent is a mixture of glycerol and water, and the mass ratio of the two is 0.25:1.

[0076] The preparation method comprises the following steps:

[0077] (1) preparing aqueous phase: mixing water, glycerol, thioneine, disodium EDTA and citric acid to obtain aqueous phase;

[0078] (2) Weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, VE acetate, sorbitan stearate and 4-butylresorcinol, mixing them and stirring in a water bath until they are completely dissolved to obtain an oil phase;

[0079] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then homogenized 8 times at 600 bar to obtain 4-butylresorcinol liposomes.

[0080] Example 4 A 4-butylresorcinol liposome and its preparation method

[0081] The composition includes the following components by weight percentage:

[0082] Caprylic / capric triglyceride 8g, hydrogenated lecithin 4g, cholesterol 1g, 4-butylresorcinol 5g, emulsifier 1g, pH adjuster 0.003g, metal ion chelator 0.05g, antioxidant 0.35g and solvent 80.597g.

[0083] The emulsifier is polyglycerol-10-isostearate.

[0084] The pH regulator is citric acid.

[0085] The metal ion chelating agent is EDTA disodium and etidronic acid, and the mass ratio of the two is 1:1.

[0086] The antioxidant is a mixture of butylated hydroxytoluene and ergothioneine, and the mass ratio of the two is 0.3:0.05.

[0087] The solvent is a mixture of glycerol and water, and the mass ratio of the two is 0.25:1.

[0088] The preparation method comprises the following steps:

[0089] (1) preparing an aqueous phase: mixing water, glycerol, ergothioneine, disodium EDTA, etidronic acid, and citric acid to obtain an aqueous phase;

[0090] (2) Weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, butylated hydroxytoluene, polyglycerol-10-isostearate and 4-butylresorcinol, mixing them and stirring them in a water bath until they are completely dissolved to obtain an oil phase;

[0091] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then homogenized 8 times at 600 bar to obtain 4-butylresorcinol liposomes.

[0092] Example 5 A 4-butylresorcinol liposome and its preparation method

[0093] The composition includes the following components by weight percentage:

[0094] Caprylic / capric triglyceride 12 g, hydrogenated lecithin 4 g, cholesterol 1.5 g, 4-butylresorcinol 5 g, emulsifier 1 g, pH adjuster 0.006 g, metal ion chelator 0.1 g, antioxidant 1.005 g and solvent 75.389 g.

[0095] The emulsifier is polyglycerol-10-myristic acid ester.

[0096] The pH regulator is citric acid.

[0097] The metal ion chelating agent is disodium EDTA.

[0098] The antioxidant is a mixture of hydroxymethoxyphenyldecanoate and sodium isoascorbate, and the mass ratio of the two is 0.005:1.

[0099] The solvent is a mixture of glycerol and water, and the mass ratio of the two is 0.25:1.

[0100] The preparation method comprises the following steps:

[0101] (1) preparing an aqueous phase: mixing water, glycerol, sodium isoascorbate, disodium EDTA, and citric acid to obtain an aqueous phase;

[0102] (2) weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, hydroxymethoxyphenyl decanone and 4-butylresorcinol, mixing them and stirring them in a water bath until they are completely dissolved to obtain an oil phase;

[0103] (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then homogenized 8 times at 600 bar to obtain 4-butylresorcinol liposomes.

[0104] Comparative Example 1

[0105] The difference from Example 5 is that cholesterol and emulsifier are not added, and an equal amount of solvent is used instead. The rest is the same as Example 5, mainly used to compare the effects of adding cholesterol and emulsifier on liposome encapsulation efficiency and transdermal performance.

[0106] Comparative Example 2

[0107] The difference from Example 5 is that no chelating agent is added, and an equal amount of solvent is used instead. The other steps are the same as Example 5, and the method is mainly used to verify the effect of the chelating agent on the color stability of liposomes.

[0108] Comparative Example 3

[0109] The difference from Example 5 is that only 1.005 g of sodium isoascorbate is added, and the other parts are the same as Example 5. This method is mainly used to verify the effect of the combined use of water-soluble and oil-soluble emulsifiers on the color stability of liposomes.

[0110] Comparative Example 4

[0111] The difference from Example 5 is that citric acid is not added, and an equal amount of solvent is used instead. The other conditions are the same as Example 5, and the method is mainly used to verify the effect of system pH on the color stability of liposomes.

[0112] Effect experiment:

[0113] 1. Liposome encapsulation efficiency detection

[0114] Detection method: Separate the unencapsulated 4-butylresorcinol from the liposome solution by ultrafiltration centrifugation and determine the liposome encapsulation efficiency. Take 200uL of the 4-butylresorcinol liposome solution diluted 5 times and place it in Ultra-15 ultrafiltration centrifuge tube (retention relative molecular weight 100kDa), centrifuge at 10000rpm for 30min. Take the filtrate in the outer tube of the ultrafiltration tube in a volumetric flask, dilute to 5mL with methanol, and use HPLC to determine and calculate the free 4-butylresorcinol content (m1). At the same time, take an appropriate amount of 4-butylresorcinol liposome solution, use methanol ultrasonic demulsification, and use HPLC to determine and calculate the total 4-butylresorcinol content of the liposome (m2). The encapsulation efficiency is calculated by the following formula:

[0115] Encapsulation rate / % = (m2-m1) / m2×100%

[0116] HPLC detection conditions: chromatographic column is C18 (200mm×4.6mm, 5μm); mobile phase is methanol-water = (60:40); detection wavelength is 280nm; flow rate is 1.0mL / min; column temperature is 25℃; injection volume is 10μL.

[0117] 2. Potential and particle size detection

[0118] Detection method: Take 20uL of 4-butylresorcinol liposomes and dilute them to 4mL with deionized water. Take 1mL of the diluted liposomes in a cuvette for particle size determination. Take the original solution and inject it into the capillary electrode for Zeta potential determination. The instrument selected is BeNano nanoparticle size and Zeta potential analyzer, and the test temperature is 25℃.

[0119] 3. Skin permeability test

[0120] Detection method: Bama Xiang pig skin was used as an in vitro transdermal model and placed between the two chambers of a vertical Franz diffusion cell, with the stratum corneum facing the supply cell and the dermis facing the receiving cell. The diameter of the receiving cell was 1 cm. 15 mL of receiving solution (PBS + 10% ethanol by volume) was added to the receiving cell with a magnetic stirrer placed in advance, so that the receiving solution was just in contact with the dermis of the skin. If there were small bubbles, they should be exhausted. 1 mL of 4-butylresorcinol liposomes was added to the sample cell. The temperature of the transdermal diffusion tester was set to 32 ° C and the stirring speed was 500 r / min. After 7 hours, the pig skin was removed, rinsed with distilled water, and cleaned with absorbent cotton. The part outside the diffusion cell was cut off, and the rest was cut into pieces with scissors, ground and placed in a centrifuge tube, 5 mL of anhydrous ethanol was added for extraction, and centrifuged after ultrasound. The supernatant was taken and the 4-butylresorcinol content was determined by HPLC, and then the skin retention of the drug was calculated.

[0121] 4. Stability test

[0122] The detection method is: after storing at room temperature under light and at 45°C in the dark for 28 days, observe the color of the liposomes and record the color from dark to light as ++++, +++, ++, +.

[0123] The test results are shown in Table 1 below.

[0124] Table 1 Test results of examples and comparative examples

[0125]

[0126] According to the results in the table, the encapsulation rate of 4-butylresorcinol in the liposomes of all the examples can reach more than 80%, meeting the quality requirements of the Chinese Pharmacopoeia for the liposome encapsulation rate. At the same time, the particle size of the liposomes in all the examples is within the range of 100-132nm, which is much smaller than the range of 140-162nm disclosed in the Chinese patent CN115836979A, showing its formula advantage.

[0127] By optimizing the experimental conditions, the encapsulation rate, transdermal performance and color stability were mainly investigated, and the formula ratio was optimized, with Example 5 being the preferred representative. Compared with Example 5, Comparative Example 1 did not add cholesterol and emulsifier. From the results in Table 1, it can be seen that the encapsulation rate of Comparative Example 1 was 79.15%, which was much lower than 88.81% of Example 5, and the skin retention amount was also reduced from 450.32ug / cm 2 Down to 285.08ug / cm 2 This indicates that under the same other conditions, the introduction of cholesterol and emulsifiers in appropriate proportions can improve the encapsulation efficiency and transdermal performance of liposomes.

[0128] Comparative Examples 2, 3 and 4 changed the antioxidant system composed of pH regulator, metal ion chelating agent and compound antioxidant on the basis of Example 5. It can be seen from the results that changing the antioxidant system has little effect on the encapsulation efficiency, particle size, potential and transdermal absorption performance of the liposome, but significantly affects the color stability of the system.

[0129] Comparative Example 2 did not add a chelating agent, and the color stability under room temperature illumination and 45°C dark conditions decreased compared to Example 5. This result shows the advantage of adding a chelating agent, which can chelate transition metal ions in the system and inhibit the catalytic oxidation reaction caused by them.

[0130] In Comparative Example 3, only water-soluble antioxidants were added, and the color stability under room temperature illumination and 45°C dark conditions decreased compared with Example 5. This shows the advantages of compounding water-soluble and oil-soluble antioxidants. Compared with single antioxidants, compounding water-soluble and oil-soluble antioxidants can respectively resist the oxidative discoloration of free unencapsulated 4-butylresorcinol in water and encapsulated 4-butylresorcinol in the oil phase, and maintain the color stability of the system.

[0131] Comparative Example 4 did not add a pH regulator, and the color stability under room temperature illumination and 45°C dark conditions decreased compared to Example 5. This shows the importance of a weakly acidic environment for the stability of a polyphenol weak acid system. In summary, adding a pH regulator, a metal ion chelating agent, and a compound antioxidant to form an antioxidant system can improve the problem that 4-butylresorcinol liposomes are easily oxidized and discolored.

[0132] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A 4-butylresorcinol liposome, characterized in that: The composition includes the following components by weight percentage: Caprylic / capric triglyceride 5-15%, hydrogenated lecithin 2-8%, cholesterol 0.1-3%, 4-butylresorcinol 1-10%, emulsifier 0.5-3%, pH adjuster 0.003-0.1%, metal ion chelator 0.01-0.5%, antioxidant 0.1-5% and solvent 55-90%.

2. The 4-butylresorcinol liposome according to claim 1, characterized in that: The composition includes the following components by weight percentage: Caprylic / capric triglyceride 8-12%, hydrogenated lecithin 4-6%, cholesterol 1-1.5%, 4-butylresorcinol 3-6%, emulsifier 1-2%, pH adjuster 0.003-0.006%, metal ion chelator 0.05-0.1%, antioxidant 0.3-1.5% and solvent 70-80%.

3. The 4-butylresorcinol liposome according to claim 2, characterized in that: The composition includes the following components by weight percentage: Caprylic / capric triglyceride 12%, hydrogenated lecithin 4%, cholesterol 1.5%, 4-butylresorcinol 5%, emulsifier 1%, pH adjuster 0.006%, metal ion chelator 0.1%, antioxidant 1.005% and solvent 75.389%.

4. The 4-butylresorcinol liposome according to claim 1, characterized in that: The emulsifier is selected from one or more of polyglycerol emulsifiers or sorbitol emulsifiers.

5. The 4-butylresorcinol liposome according to claim 1, characterized in that: The emulsifier is one or more selected from polyglycerol-10-myristic acid ester, polyglycerol-10-lauric acid ester, polyglycerol-10-stearate, sorbitan sesquioleate and sorbitan stearate.

6. The 4-butylresorcinol liposome according to claim 1, characterized in that: The pH regulator is citric acid.

7. The 4-butylresorcinol liposome according to claim 1, characterized in that: The metal ion chelating agent is selected from one or more of disodium EDTA, disodium edetate and etidronic acid.

8. The 4-butylresorcinol liposome according to claim 1, characterized in that: The antioxidant is selected from oil-soluble antioxidants and / or water-soluble antioxidants.

9. The 4-butylresorcinol liposome according to claim 1, characterized in that: The oil-soluble antioxidant is selected from one or more of vitamin E, VE acetate, butylated hydroxyanisole, butylated hydroxytoluene, tert-butylhydroquinone, tert-butylhydroquinone, hydroxymethoxyphenyl decanone, carnosic acid, guaiacol, and propyl gallate; the water-soluble antioxidant is selected from one or more of sodium pyrosulfite, sodium bisulfite, sodium phytate, ergothioneine, ascorbic acid, isoascorbic acid and its salts.

10. The 4-butylresorcinol liposome according to claim 9, characterized in that: The oil-soluble antioxidant is selected from one or more of VE acetate, butylated hydroxytoluene, and hydroxymethoxyphenyl decanone; the water-soluble antioxidant is selected from one or more of sodium pyrosulfite, ergothioneine, and sodium isoascorbate.

11. The 4-butylresorcinol liposome according to claim 10, characterized in that: The antioxidant is a mixture of hydroxymethoxyphenyl decanone and sodium isoascorbate, and the mass ratio of the two is 0.001-0.01:

1.

12. The 4-butylresorcinol liposome according to claim 1, characterized in that: The solvent is a mixed solution of water and glycerol, and the mass ratio of glycerol to water is 0.05-1:

1.

13. The method for preparing 4-butylresorcinol liposomes according to any one of claims 1 to 12, characterized in that: The steps include: (1) preparing an aqueous phase: mixing water, glycerol, a water-soluble antioxidant, a pH adjuster and a chelating agent to obtain an aqueous phase; (2) weighing the prescribed amount of caprylic / capric triglyceride, hydrogenated lecithin, cholesterol, emulsifier, oil-soluble antioxidant and 4-butylresorcinol, mixing them and stirring them in a water bath until they are completely dissolved to obtain an oil phase; (3) The aqueous phase is added to the oil phase while stirring to form a primary emulsion, and the primary emulsion is then treated with a high-pressure homogenizer to obtain 4-butylresorcinol liposomes.

14. Use of the 4-butylresorcinol liposome according to any one of claims 1 to 12 in the preparation of cosmetics.

Images