Liposome taking sodium lauroyl lactylate as substrate and preparation method thereof

Abstract

The invention provides lipidosome with sodium lauroyl lactylate as a substrate and a preparation method of the lipidosome, and belongs to the technical field of cosmetics. The liposome is prepared from the following components in percentage by weight: 5 to 20 percent of sodium lauroyl lactylate, 1 to 10 percent of cholesterol lauroyl glutamate, 15 to 25 percent of polyhydric alcohol, 1 to 5 percent of surfactant, 1 to 5 percent of auxiliary oil phase agent, 1 to 10 percent of active matter and the balance of buffer solution. The sodium lauroyl lactylate is used as a substrate, hydrogen bonds and hydrophobic interaction between proteins are reduced through interaction between lactoyl groups in the structure of the sodium lauroyl lactylate and the proteins in the cuticle of the skin, so that the viscosity of the cuticle is reduced, the permeability of the skin is improved, the sodium lauroyl lactylate is matched with the cholesteryl lauroyl glutamate, the lipid compatibility is improved, and the skin care effect is improved. Active matters in the skin care product can be promoted to more effectively permeate into the deep layer of the skin, so that the permeation efficiency of the active matters is improved.

Description

Technical Field

[0001] The invention relates to the technical field of cosmetics, and in particular to a liposome based on sodium lauroyl lactylate and a preparation method thereof. Background Art

[0002] In today's society, material life is constantly enriched. For many products such as cosmetics, the high demands of consumers and the new selling points expected by manufacturers have prompted researchers to develop and apply more ingredients to meet different needs. However, the solubility of most functional active ingredients is extremely low, and the amount in the system is not enough to play its function. How to improve the solubility of active ingredients is the key to product development.

[0003] Liposome is an artificial membrane, which is a closed vesicle with a bilayer structure spontaneously formed in water by amphiphilic molecules such as phospholipids and sphingolipids, with a diameter of 25-1000nm. Compared with traditional cosmetics, liposomes can encapsulate active substances that are difficult to dissolve, and due to their amphiphilicity, they can deliver active substances to the deep layers of the skin, and have broad application prospects in the fields of cosmetics and medicine. Although liposomes can improve the bioavailability of certain active substances, not all active substances are suitable for delivery through liposomes. For example, the encapsulation efficiency of active substances such as vitamin C in liposomes is low, or their release characteristics may not meet expectations, thereby affecting their bioavailability and therapeutic effects. At the same time, the membrane layer of liposomes has a certain fluidity, which makes liposomes easily affected by external factors, such as temperature, pH value, etc., resulting in aggregation precipitation or leakage of embedded components. In addition, unsaturated fatty acids in lipid molecules are also prone to hydrolysis or oxidation, resulting in flocculation or chemical instability of liposomes, thereby affecting their storage stability and shelf life.

[0004] Soy lecithin is often used as an emulsifier to prepare liposomes because it is easily absorbed by human skin and hair, has permeability-enhancing properties, and has strong emulsifying properties. However, the existing soybean lecithin produced by different manufacturers is quite different, which leads to differences in the smell, color, and stability of the prepared liposomes. Using it to prepare liposomes not only makes the base of the liposomes relatively single and expensive, but also greatly increases the research and development and production costs, which is not conducive to the development and utilization of active substances.

[0005] Based on this, if a liposome with high transdermal absorption efficiency and high encapsulation rate can be provided, it will be beneficial to the application of liposomes and provide the possibility of expanding new indications. Summary of the invention

[0006] In view of the defects of the prior art, the present invention designs a liposome based on sodium lauroyl lactylate and a preparation method thereof, which can not only improve the skin permeability of the active substance, but also improve the stability of the liposome, which is conducive to better achieving the effect of the active substance.

[0007] In order to achieve the above purpose, the present invention solves the technical problem by adopting the following technical solutions: In a first aspect, the present invention provides a liposome based on sodium lauroyl lactylate, which comprises, by weight percentage, 5-20% sodium lauroyl lactylate, 1-10% cholesterol lauroyl glutamate, 15-25% polyol, 1-5% surfactant, 1-5% oil phase agent, 1-10% active ingredient, and the balance is buffer.

[0008] In some of the embodiments, the composition comprises, by weight percentage, 10-12% sodium lauroyl lactylate, 2-6% cholesterol lauroyl glutamate, 20-22% polyol, 2-3% surfactant, 2-3% oil phase agent, 2-5% active ingredient, and the balance is buffer.

[0009] In some of the embodiments, the composition comprises, by weight percentage, 11% sodium lauroyl lactylate, 4% cholesterol lauroyl glutamate, 21% polyol, 2.5% surfactant, 3% oil phase agent, 2-5% active ingredient, and the balance is buffer.

[0010] In some embodiments, the polyol includes one or more of glycerol, propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, and 1,2-hexanediol.

[0011] For example, it may be a combination of glycerol, propylene glycol, 1,3-butanediol, 1,2-pentanediol and 1,2-hexanediol; it may also be a combination of glycerol, propylene glycol and 1,3-butanediol; or a combination of 1,3-butanediol, 1,2-pentanediol and 1,2-hexanediol.

[0012] In some embodiments, the surfactant includes one or more of decyl glucoside and lauryl glucoside.

[0013] In some embodiments, the oil phase agent includes one or more of dibutyl adipate, plant squalane, propylene glycol, 1,3-butylene glycol, and 1,2-hexanediol.

[0014] For example, it may be a combination of dibutyl adipate, plant squalane, propylene glycol, 1,3-butanediol and 1,2-hexanediol; it may also be a combination of dibutyl adipate, propylene glycol and 1,3-butanediol; or a combination of plant squalane, 1,3-butanediol and 1,2-hexanediol.

[0015] In some embodiments, the active ingredients include one or more of retinol, resveratrol, coenzyme Q10, glabridin, and Va propionate.

[0016] For example, it may be a combination of retinol, resveratrol, coenzyme Q10, glabridin and Va propionate; it may also be a combination of retinol, resveratrol and glabridin; or a combination of Va propionate, resveratrol and coenzyme Q10.

[0017] In some embodiments, the buffer comprises one or more of a phosphate buffer and a lactic acid sodium lactate buffer; and the pH value of the buffer is 5.5-7.5.

[0018] In a second aspect, the liposome encapsulation efficiency provided by the invention is >85%.

[0019] In a third aspect, the present invention provides a method for preparing liposomes, comprising the following steps: First, sodium lauroyl lactylate, cholesterol lauroyl glutamate and polyol are mixed and stirred evenly, and then surfactants and oil phase agents are added until the active ingredients are completely dissolved. Then, buffer solution is added, and the mixture is stirred and aged in a water bath at 75-85°C for 2-4 hours. After aging, water is added and the mixture is cooled to room temperature to obtain liposomes.

[0020] Compared with the prior art, the present invention has the following beneficial effects: The present invention uses sodium lauroyl lactylate as a base, and the lactyl group in its structure interacts with proteins in the stratum corneum of the skin, thereby reducing hydrogen bonds and hydrophobic interactions between proteins, thereby reducing the viscosity of the stratum corneum and increasing the permeability of the skin. It is combined with cholesterol lauroyl glutamate to improve lipid compatibility, and can make the active ingredients in the skin care products penetrate into the deep layers of the skin more effectively, thereby improving the penetration efficiency of the active ingredients. At the same time, additives such as polyols, surfactants, and oil-aiding agents further improve the encapsulation effect of the liposome and the penetration of the active ingredients.

[0021] In addition, the method for preparing liposomes of the present invention is simple to operate, low in cost, suitable for large-scale industrial production, and has good adaptability of the matrix formula, safe raw materials, stable application, and the prepared liposomes have a large carrying capacity of active substances. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solution of the present invention, the drawings required for use in the implementation mode will be briefly introduced below. Obviously, the drawings described below are only some implementation modes of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 1 is a graph showing the in vitro transdermal absorption test results of different liposomes in the embodiments of the present invention.

[0024] Figure 2 Graph showing the standard curve of retinol in the embodiment of the present invention. DETAILED DESCRIPTION

[0025] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with specific embodiments. 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.

[0026] In the present invention, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are considered continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0027] In the present invention, there is no particular limitation on the specific dispersion and stirring treatment methods.

[0028] In the present invention, the test methods used are conventional methods unless otherwise specified; the materials, reagents, etc. used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0029] In the present invention, the term "aging" used refers to allowing the solution to stand for a period of time under certain conditions after the precipitation is complete during the precipitation process.

[0030] The term "normal temperature" refers to normal temperature or room temperature, which is 25±5°C.

[0031] The term "encapsulation efficiency" refers to the percentage of the encapsulated substance (such as active substance) in the liposome suspension to the total amount of the substance, reflecting the extent to which the active substance is encapsulated by the carrier.

[0032] A liposome based on sodium lauroyl lactylate, the formula of which is shown in Table 1 below by weight percentage: Table 1 Liposome formulation Example 1 1. A liposome based on sodium lauroyl lactylate, the specific formula of which is shown in Table 1 above.

[0033] In this embodiment, the polyol is 1,2-pentanediol; the surfactant is decyl glucoside; the oil-aiding phase agent is 1,2-hexanediol; the active substance is retinol, and the buffer is phosphate buffer with a pH of 6.0.

[0034] 2. A method for preparing liposomes based on sodium lauroyl lactylate, comprising the following steps: 1. Mix sodium lauroyl lactylate, cholesterol lauroyl glutamate and polyol and stir evenly until it becomes light yellow and clear.

[0035] 2. Stir and add surfactant, oil phase agent and active ingredients until they are completely dissolved and clear.

[0036] 3. Slowly add the buffer solution while stirring. Continue stirring until the material becomes a clear liquid and stop stirring.

[0037] 4. Seal and slowly stir in a water bath at 80°C for 3 hours, then cool to room temperature to obtain clarified liposomes.

[0038] Example 2 1. A liposome based on sodium lauroyl lactylate, the specific formula of which is shown in Table 1 above.

[0039] In this embodiment, the polyol is propylene glycol; the surfactant is lauryl glucoside; the oil phase agent is dibutyl adipate; the active substance is retinol, and the buffer is lactic acid-sodium lactate buffer, pH=5.5.

[0040] 2. A method for preparing liposomes based on sodium lauroyl lactylate, comprising the following steps: 1. Mix sodium lauroyl lactylate, cholesterol lauroyl glutamate and polyol and stir evenly until it becomes light yellow and clear.

[0041] 2. Stir and add surfactant, oil phase agent and active ingredients until they are completely dissolved and clear.

[0042] 3. Slowly add the buffer solution while stirring. Continue stirring until the material becomes a clear liquid and stop stirring.

[0043] 4. Seal and slowly stir in a water bath at 85°C for 2 hours. After aging, take out and let stand to room temperature to obtain clarified liposomes.

[0044] Example 3 1. A liposome based on sodium lauroyl lactylate, the specific formula of which is shown in Table 1 above.

[0045] In this embodiment, the polyol is 1,3-butanediol; the surfactant is decyl glucoside; the oil phase agent is dibutyl adipate; the active substance is retinol, and the buffer is phosphate buffer with a pH of 7.5.

[0046] 2. A method for preparing liposomes based on sodium lauroyl lactylate, comprising the following steps: 1. Mix sodium lauroyl lactylate, cholesterol lauroyl glutamate and polyol and stir evenly until it becomes light yellow and clear.

[0047] 2. Stir and add surfactant, oil phase agent and active ingredients until they are completely dissolved and clear.

[0048] 3. Slowly add the buffer solution while stirring. Continue stirring until the material becomes a clear liquid and stop stirring.

[0049] 4. Seal and slowly stir in a water bath at 75°C for 4 hours. After aging, take out and let stand to room temperature to obtain clarified liposomes.

[0050] Example 4 The difference between Example 4 and Example 1 is that the active ingredient in Example 4 is resveratrol, and the other aspects are the same.

[0051] Example 5 The difference between Example 5 and Example 1 is that the active substance in Example 5 is coenzyme Q10, and the other aspects are the same.

[0052] Example 6 The difference between Example 6 and Example 1 is that the active substance in Example 6 is glabridin, and the other contents are the same.

[0053] Example 7 The difference between Example 7 and Example 1 is that the active substance in Example 7 is Va propionate (vitamin A propionate), and the rest are the same.

[0054] Comparative Example 1-2 The formula of a liposome based on sodium lauroyl lactylate is shown in Table 1 above, and its specific raw materials and preparation method are the same as those in Example 1.

[0055] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that sodium lauroyl lactylate is not added in Comparative Example 3, and the other contents are the same.

[0056] Comparative Example 4 The difference between Comparative Example 4 and Example 1 is that an equal amount of soybean lecithin is used to replace sodium lauroyl lactylate in Comparative Example 4, and the other contents are the same.

[0057] Comparative Example 5 The difference between Comparative Example 5 and Example 1 is that Comparative Example 5 uses an equal amount of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate to replace sodium lauroyl lactylate, and the other contents are the same.

[0058] Comparative Example 6 The difference between Comparative Example 6 and Example 1 is that cholesterol lauroyl glutamate is not added in Comparative Example 6, and the other contents are the same.

[0059] Comparative Example 7 The difference between Comparative Example 7 and Example 1 is that Comparative Example 8 uses an equal amount of cholesterol / octyldodecanol lauroyl glutamate to replace cholesterol lauroyl glutamate, and the other contents are the same.

[0060] Test Example 1 1. Product water solubility test The liposomes prepared in Examples 1-3 and Comparative Examples 1-7 were respectively formulated into aqueous solutions with a mass fraction of 1% and 10% with deionized water, and the appearance of the liposomes before formulation, the 1% aqueous solution, and the 10% aqueous solution were observed.

[0061] Table 2 Water solubility test results of different liposomes As can be seen from Table 2, the liposome prepared in the present invention is an orange clear liquid, and as the amount of water increases, the liposome is diluted, resulting in a lighter color, indicating that the liposome of the present invention has good water solubility.

[0062] 2. Stability Test Place the samples to be tested in a constant temperature insulation box and conduct cold resistance, heat resistance, and hot and cold cycle tests respectively.

[0063] Cold resistance: -15℃, 3 months. After returning to room temperature, observe whether there are changes such as precipitation, flocculation and stratification.

[0064] Heat resistance: 45℃, 3 months. After returning to room temperature, observe whether there are changes such as precipitation, flocculation and stratification.

[0065] Hot and cold cycle: 45℃, room temperature, -15℃, 24 hours at each temperature, one week as one cycle, 6 cycles, observe whether there are changes such as precipitation, flocculation and stratification after the cycle.

[0066] Table 3 Temperature stability test results of different liposomes As shown in Table 3, after the liposomes passed the temperature test of cold resistance, heat resistance test and cold and hot cycle test, compared with comparative examples 3-7, the liposomes of Examples 1-3 did not show precipitation, stratification and the like, indicating that the liposomes of the present invention have good stability.

[0067] Test Example 2 1. In vitro percutaneous absorption test The Franz diffusion cell transdermal absorption test was carried out in accordance with the national standard GB-T 27818-2011 “In vitro test method for skin absorption of chemicals”.

[0068] The pig skin (20cm×20cm, skin thickness of 0.8mm, pig age of about 1 month) with the subcutaneous fat layer and connective tissue peeled off was fixed between the supply chamber and the receiving chamber of the Franz diffusion cell, and then the sample to be tested was added to the surface of the pig skin, and 0.01mol / L PBS buffer solution was added to the receiving solution. The solution was stirred at a constant temperature of 37℃ and 500r / min, and 0.2mL of the receiving solution was collected at 2, 4, 6, 8, 12, and 24 hours, respectively, and 0.2mL of PBS buffer solution was supplemented. The samples obtained were filtered with a 0.22 μm filter membrane, and the liposome content was detected by HPLC.

[0069] Chromatographic column: C18 column (4.6×250mm, 5μm); mobile phase: 0.2% acetic acid aqueous solution (A)-methanol (B) (50%; 50%); flow rate: 1.0mL / min; detection wavelength: 325nm, column temperature: 30℃; injection volume: 10μL.

[0070] Standard curve drawing: Retinol was prepared into a 1 mg / mL retinol solution with methanol, and then diluted into 0.05, 0.1, 0.2, 0.4, 0.6, and 0.8 mg / mL standard solutions. The retinol concentration was measured at 325 nm, and the peak area was used as the y-axis and the target (retinol, mg / mL) concentration was used as the x-axis to draw a standard curve for linear regression analysis. Figure 2 As shown, the linear regression equation is: Y=39.972X+0.5831, R2=0.9911.

[0071] Depend on Figure 1 It can be seen that the liposomes prepared in Examples 1-3 have a much higher accumulation of active substances than those prepared in Comparative Examples 1-7 after 24 hours of in vitro transdermal absorption, indicating that the liposomes of the present invention have better transdermal absorption performance and can more effectively deliver active substances to the skin.

[0072] 2. Encapsulation efficiency test Liposome sample treatment: 1 mL of the prepared liposomes was centrifuged at 5000 rpm for 15 min, 8 mL of methanol was added to the supernatant, and then ultrasonic treatment was performed at 400 W for 5 min. The supernatant was filtered through a 0.22 μm filter membrane, and the filtrate was used as the test solution.

[0073] The liposomes prepared in Examples 1-3 and Comparative Examples 1-7 were treated according to the above method, and the active substance content in the liposomes was determined by HPLC, and the encapsulation efficiency was calculated. The calculation formula is as follows: (1); Wherein, Mencapsulated represents the mass of active substance encapsulated into liposomes (mg); Mtotal represents the amount of active substance input (mg).

[0074] Table 4 Encapsulation efficiency test results of different liposomes It can be seen from Table 4 that the encapsulation rate of Examples 1-3 is significantly higher than that of Comparative Examples 1-7, higher than 85%. It can be seen from Comparative Examples 3-5 and Example 1 that, under the same mass, the encapsulation rate of the liposomes prepared by sodium lauroyl lactylate is higher, and the amount of active substances encapsulated is much greater than that of soybean lecithin, indicating that the present invention cooperates with each other through various raw materials, and the quality of the liposomes prepared within a certain range is higher, and the active substances can be effectively encapsulated in the liposomes, which is beneficial to improve the efficacy of the active substances.

[0075] In addition, this scheme selects liposomes encapsulating retinol as the test sample. It is worth noting that the liposomes have a wide range of applicability and are not limited to encapsulating retinol. In fact, under the protection method of the present invention, as in Examples 4-7, the active substances therein are replaced, and other active substances such as resveratrol and coenzyme Q10 can also be encapsulated, and when encapsulating these active substances, a high encapsulation rate can still be maintained, showing good encapsulation performance of active substances.

[0076] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A liposome based on sodium lauroyl lactylate, characterized in that: By weight percentage, the invention comprises 5-20% sodium lauroyl lactylate, 1-10% cholesterol lauroyl glutamate, 15-25% polyol, 1-5% surfactant, 1-5% oil phase agent, 1-10% active substance, and the balance is buffer solution.

2. The liposome based on sodium lauroyl lactylate according to claim 1, characterized in that By weight percentage, the invention comprises 10-12% sodium lauroyl lactylate, 2-6% cholesterol lauroyl glutamate, 20-22% polyol, 2-3% surfactant, 2-3% oil phase agent, 2-5% active matter, and the balance is buffer solution.

3. The liposome based on sodium lauroyl lactylate according to claim 1, characterized in that: By weight percentage, the invention comprises 11% sodium lauroyl lactylate, 4% cholesterol lauroyl glutamate, 21% polyol, 2.5% surfactant, 3% oil phase agent, 2-5% active matter, and the balance is buffer solution.

4. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 3, characterized in that: The polyol includes one or more of glycerol, propylene glycol, 1,3-butanediol, 1,2-pentanediol, and 1,2-hexanediol.

5. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 3, characterized in that: The surfactant includes one or more of decyl glucoside and lauryl glucoside.

6. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 3, characterized in that: The auxiliary oil phase agent includes one or more of dibutyl adipate, plant squalane, propylene glycol, 1,3-butylene glycol, and 1,2-hexanediol.

7. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 3, characterized in that: The active ingredients include one or more of retinol, resveratrol, coenzyme Q10, glabridin, and Va propionate.

8. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 3, characterized in that: The buffer comprises a phosphate buffer and / or a lactic acid sodium lactate buffer; The pH value of the buffer solution is 5.5-7.

5.

9. The liposome based on sodium lauroyl lactylate according to any one of claims 1 to 8, characterized in that The encapsulation efficiency of the liposome is>85%.

10. A method for preparing liposomes based on sodium lauroyl lactylate as claimed in any one of claims 1 to 8, characterized in that: First, sodium lauroyl lactylate, cholesterol lauroyl glutamate and polyol are mixed and stirred evenly, and then surfactants and oil phase agents are added until the active ingredients are completely dissolved. Then, buffer solution is added, and the mixture is stirred and aged in a water bath at 75-85°C for 2-4 hours. After aging, water is added and the mixture is cooled to room temperature to obtain liposomes.

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