A liposome composition and its application in cosmetics

Abstract

The present invention relates to a novel liposome composition and its application in cosmetics, and the liposome composition comprises an active ingredient, sodium stearoyl glutamate and isopropyl lauroyl sarcosinate.

Description

Technical Field

[0001] The present invention relates to a novel liposome composition and its application in cosmetics. The liposome composition comprises a combination of an active ingredient, sodium stearoyl glutamate, and isopropyl lauroylsarcosinate. Background Art

[0002] In the field of cosmetics, some active ingredients have the characteristics of low solubility, high irritation, and difficulty in transdermal absorption, which severely limits their applications. To solve this problem, the prior art has developed a technology of encapsulating and loading these active ingredients with liposomes.

[0003] Liposomes were first proposed as a biological model by Bangham et al. in 1965. They are carriers with a closed vesicle structure formed with lecithin, cholesterol, etc. as membrane materials. Among them, hydrophilic groups are located on the surface of the membrane and lipophilic groups are located in the middle of the membrane. There is a certain space between each layer of the membrane, which can encapsulate hydrophobic drugs. As a novel carrier, liposomes have the characteristics of good stability, strong targeting, controlled release, and no immunotoxicity. In the 1980s, liposomes were mainly applied in the pharmaceutical industry and have gradually been applied in the field of cosmetics due to their unique properties.

[0004] However, common liposomes have a series of problems, including low loading capacity of active ingredients and poor stability, which greatly limit their applications in cosmetics. Liposomes of the prior art generally can only load less than 5% of active ingredients. For example, in CN104983591B, the loading amount of the active ingredient β-carotene is 0.1 - 1%; in CN201510400196.8, the loading amount of the anti-wrinkle and moisturizing active ingredient is 0.4 - 1.5%.

[0005] Therefore, in the field of cosmetics, there is a need for a novel liposome composition that can solve the problems of low loading capacity of liposomes for active ingredients and instability under normal storage conditions and in cosmetic formulations.

[0006] Brief Description of the Drawings

[0007] Figure 1-10 They are cryo-electron microscopy photographs of liposomes A - J respectively.

[0008] Figure 11-20 They are microscope photographs of liposomes A - J respectively. Summary of the Invention

[0009] The inventors of the present invention have found through research that the combination of sodium stearoyl glutamate and isopropyl lauroylsarcosinate plays an obvious synergistic effect in improving the loading capacity and stability of active ingredients in liposomes.

[0010] Accordingly, on the one hand, the present invention relates to the use of a combination of sodium stearoyl glutamate and isopropyl lauroylsarcosinate in a liposome composition, wherein the combination of sodium stearoyl glutamate and isopropyl lauroylsarcosinate can improve the loading amount and stability of the active ingredient in the liposome.

[0011] On the other hand, the present invention relates to a liposome composition comprising an active ingredient, sodium stearoyl glutamate and isopropyl lauroylsarcosinate.

[0012] The sodium stearoyl glutamate is an emulsifier and isopropyl lauroylsarcosinate is a lipid, and they are both known compounds and are commercially available. For example, sodium stearoyl glutamate can be purchased from BASF and isopropyl lauroylsarcosinate can be purchased from Ajinomoto Co., Inc.

[0013] In the liposome composition, the content of sodium stearoyl glutamate is about 0.1 - 3%, preferably about 0.3 - 2%; the content of isopropyl lauroylsarcosinate is about 1 - 20%, preferably about 3 - 15%, more preferably about 5 - 10%; the contents are both based on the total weight of the liposome composition.

[0014] The active ingredient to be loaded in the liposome composition is known in cosmetics and includes, for example, extracts of Ormosia henryi bark, resveratrol, curcumin, ceramides, phenethyl resorcinol, retinol, licorice flavonoids, extract of Glycyrrhiza glabra root, quercetin, quercitrin, baicalin, baicalein, silymarin, kaempferol, ubiquinone, aloesin, glabridin, pentahydroxyflavone, tetrahydropiperine, pterostilbene, hesperidin, asiaticoside, salicylic acid and ferulic acid, etc. In the liposome composition of the present invention, preferred active ingredients include phenethyl resorcinol, resveratrol and extracts of Ormosia henryi bark.

[0015] The liposome composition generally further comprises polyols, co-emulsifiers, membrane modifiers and water, etc., and may further comprise other lipids and emulsifiers, etc.

[0016] The polyols include but are not limited to diols and triols, such as 1,2-pentanediol, isopentanediol, glycerol, 1,3-butanediol, dipropylene glycol and 1,3-propanediol, sorbitol. Preferably, the polyol is selected from 1,2-pentanediol, 1,3-butanediol and 1,3-propanediol. The content of the polyol is known in the art and is usually about 1 - 20%, preferably about 7 - 15%, based on the total weight of the liposome composition.

[0017] The co-emulsifier is a commonly used co-emulsifier in cosmetics, and it can be selected from glycerol fatty acid esters (for example, glyceryl stearate SE, glyceryl myristate, glyceryl undecylenate, and glycerol monostearate), L-lysine, polyvinyl alcohol, or sodium alginate, phospholipid emulsifiers (for example, lecithin, hydrogenated lecithin, hydroxylated lecithin, lysophosphatidylcholine, hydrogenated lysophosphatidylcholine), etc. Preferred co-emulsifiers are selected from glycerol monostearate, hydrogenated lecithin, and lecithin.

[0018] The membrane modifier is those commonly used in cosmetics, including but not limited to sterols, such as plant sterol mixtures, β-sitosterol, cholesterol, campesterol, sitostanol, ergosterol, and stigmasterol. Preferably, the membrane modifier includes a plant sterol mixture and β-sitosterol. The content of the membrane modifier is known in the art, and it is usually about 0.1-2%, preferably about 0.2-1%, based on the total weight of the liposome composition.

[0019] The other lipids are those commonly used in cosmetics, including but not limited to esters, such as cetyl ethylhexanoate, ethylhexyl palmitate, isopropyl myristate, triglyceride of octanoic acid / decanoic acid, dicaprylyl carbonate, coco-caprylate / caprate, glycerol monostearate; alcohols, such as octyldodecanol, behenyl alcohol, cetyl alcohol, and stearyl alcohol, etc.; hydrocarbons, such as isocetane and hydrogenated polyisobutene, etc. Preferably, the other lipids are selected from ethylhexyl palmitate, isopropyl myristate, triglyceride of octanoic acid / decanoic acid, glycerol monostearate, behenyl alcohol, and stearyl alcohol. The content of the other lipids is known in the art, and it is usually about 10-30%, preferably about 15-25%, based on the total weight of the liposome composition.

[0020] The other emulsifiers are emulsifiers commonly used in cosmetics, and they can be selected from nonionic emulsifiers, such as glucoside emulsifiers (for example, cetearyl glucoside), polyether emulsifiers (for example, steareth-21), polyglycerol emulsifiers (for example, polyglyceryl-3 methylglucose distearate); anionic emulsifiers, such as carboxylates (for example, sodium stearoyl glutamate, sodium stearoyl lactate, etc.), sulfate esters (for example, sodium cetearyl sulfate), phosphate esters (for example, potassium cetyl phosphate, stearyl phosphate), etc. Preferably, the other emulsifiers are selected from cetearyl glucoside, steareth-21, and polyglyceryl-3 methylglucose distearate. The content of the other emulsifiers is known in the art, and it is usually about 0.5-7%, preferably about 1-4%, based on the total weight of the liposome composition.

[0021] In another aspect, the present invention provides a method for preparing the above liposome composition, which includes the following steps:

[0022] a. At a temperature of 60 - 90 °C, preferably 75 - 85 °C, mix polyol, sodium stearoyl glutamate, co-emulsifier and water to obtain a uniform mixture A;

[0023] b. At a temperature of 60 - 90 °C, preferably 75 - 85 °C, pre-mix isopropyl lauroyl sarcosinate, film modifier, co-emulsifier, then add the active ingredient thereto and further mix under stirring to obtain a uniform mixture B;

[0024] c. Under stirring, mix mixture A and mixture B to obtain a uniform mixture C; and

[0025] d. Treat mixture C with a high-pressure microfluidization homogenizer to obtain a liposome composition, wherein the pressure of the high-pressure microfluidization homogenizer is about 10,000 - 30,000 psi, preferably about 20,000 - 30,000 psi, and the number of cycles is about 2 - 5 times, preferably about 3 times.

[0026] In the above step a, other emulsifiers may be further added to help obtain a uniform mixture A. To accelerate the mixing, the mixing may be carried out under stirring, and the stirring speed may be about 100 - 1000 rpm, preferably about 300 - 800 rpm.

[0027] In the above step b, the stirring speed may be about 100 - 1000 rpm, preferably about 200 - 500 rpm, more preferably about 300 - 400 rpm, and the stirring time may be about 10 - 30 min, preferably about 20 - 30 min. In the pre-mixing, to accelerate the mixing, the pre-mixing may be carried out under stirring, and the stirring speed may be about 100 - 1000 rpm, preferably about 300 - 800 rpm.

[0028] In the above step c, the stirring speed may be about 500 - 1000 rpm, preferably about 700 - 900 rpm, and the stirring time may be about 5 - 10 min, preferably about 8 - 10 min. Step c is generally carried out at room temperature.

[0029] The above step d is usually carried out at room temperature.

[0030] Due to the adoption of the high-pressure microfluidization technology in the preparation method of the present invention, the purposes of homogenization and refinement are achieved by means of high-speed impact, shearing and cavitation, and it has the advantages of simple operation, clean and safe, easy for continuous production and obtaining a stable liposome composition.

[0031] The liposomal composition of the present invention is generally a uniform light yellow liquid with a blue sheen, having a particle size of about 100 - 500 nm, preferably about 100 - 300 nm, more preferably about 100 - 200 nm, and most preferably 100 - 120 nm. The liposomal composition of the present invention has good stability, and its particle size can remain stable for a long time. For example, the liposomal composition can be stable for at least one year, at least two years, or at least three years at room temperature.

[0032] Compared with liposomes of the prior art, the liposomal composition of the present invention can significantly contain (load) more active ingredients. For example, the liposomal composition of the present invention can load more than 5%, preferably about 5 - 35%, more preferably about 5 - 30%, and most preferably about 15 - 25% of active ingredients, based on the total weight of the liposomal composition. Moreover, the encapsulation efficiency of the active ingredients in the liposomal composition of the present invention is greater than 70%, preferably greater than 80%, more preferably greater than 90%, and even preferably greater than 95%, based on the total weight of the loaded active ingredients.

[0033] The liposomal composition of the present invention is used as an intermediate in a cosmetic composition to provide an active ingredient that can be effectively utilized. The liposomal composition of the present invention has good stability, and its particle size can remain stable for a long time, which is very important for its subsequent use in a cosmetic composition and thus for fully exerting the efficacy of the active ingredient.

[0034] In another aspect, the present invention provides a cosmetic composition comprising the above liposomal composition. Generally, the content of the liposomal composition in the cosmetic composition is about 3 - 20%, preferably about 5 - 15%, based on the total weight of the cosmetic composition.

[0035] The cosmetic composition can be a cosmetic composition in any dosage form, such as a moisturizing liquid, essence, lotion, cream, foundation, sunscreen cream, spray, etc.

[0036] In addition to the liposomal composition, the cosmetic composition may optionally contain ingredients commonly used in cosmetics, including but not limited to active components such as emollients, humectants, and skin conditioners, vehicles such as diluents, dispersants, solvents or carriers, surfactants, excipients such as emulsifiers, thickeners, preservatives, fragrances, and pH regulators, which are known to those skilled in the art and can be specifically selected according to needs for their types and amounts.

[0037] The cosmetic composition of the present invention can be prepared by any suitable method known in the art. For example, equipment such as dissolution tanks, emulsifying kettles, dispersers, and transfer pumps commonly used in the cosmetic field can be used to prepare according to the processes known in the art. For example, water-soluble substances can be first put into the water-phase dissolution kettle, and oil-soluble substances can be put into the oil-phase dissolution kettle. The temperatures of the two kettles are respectively heated to about 80 °C. For raw materials that are prone to caking, they can be pre-dispersed with a disperser first; after dissolution is completed, the oil phase and the water phase are delivered to the emulsifying kettle for homogenizing emulsification for about 5 - 15 min; after emulsification is completed, the temperature of the material is lowered to 45 °C, and the liposome composition is added and stirred for 5 min. Continue to cool to room temperature. Optionally, flavors, preservatives, etc. are added, and the pH of the product is adjusted as needed; after relevant test indicators are qualified, it can be filled and shipped. The above preparation process is merely illustrative, and those skilled in the art can increase, decrease, or adjust according to the dosage form requirements, so as to prepare various dosage forms such as sprays, emulsions, creams, ointments, or gels. Example

[0038] The present invention will be further described in detail below in conjunction with examples.

[0039] Example 1: Preparation of the liposome composition of the present invention and the control liposome composition

[0040] In this example, the liposome composition of the present invention and the control liposome composition with the following formulations were prepared.

[0041] Table 1

[0042]

[0043] Table 1'

[0044] Component (wt%) Liposome F Liposome I Liposome J Sodium stearoyl glutamate 0.8 0.8 0.8 Isopropyl lauroylsarcosinate 15 15 15 Hydrogenated lecithin 5 5 5 Propylene glycol 10 10 10 Caprylic / capric triglyceride 25 25 25 Glyceryl stearate 1.5 1.5 1.5 Phytosterols 0.5 0.5 0.5 Ormosia henryi bark extract 20 0 0 Kaempferol 0 20 0 Dihydro-avenanthramide 0 0 20 Water 22.5 22.5 22.5

[0045] The preparation process of the above liposome composition is as follows:

[0046] a. Weigh propylene glycol, sodium stearoyl glutamate, hydrogenated lecithin, and deionized water, and stir and mix at 75 °C and 500 rpm for 20 min to obtain Phase A;

[0047] b. Weigh isopropyl lauroyl sarcosinate, phytosterols, caprylic / capric triglyceride, and glycerol monostearate, mix at 75 °C and 500 rpm for 10 min, and then add the active ingredient (such as extract of Ormosia henryi Prain bark or resveratrol or phenethyl resorcinol, etc.) thereto and continue to stir and mix for 10 min to obtain Phase B;

[0048] c. At room temperature (and under stirring at 800 rpm), mix Phase A and Phase B to obtain the mixed liquid C;

[0049] d. Then the mixed solution C was added to a high-pressure microfluidizer and circulated three times at a pressure of 20,000 psi to obtain the above liposome composition.

[0050] Example 2: Testing the active ingredient loading and encapsulation efficiency in liposome compositions

[0051] The loading capacity was tested by ultraviolet absorption spectrophotometry after dilution with ethanol. Specifically, 100uL of the liposome composition was diluted 10,000 times with ethanol to prepare a sample. The reference substance (without active ingredient) was prepared by the same method and fully dispersed using an ultrasonic disperser. The sample was then filtered through a 0.22μm filter membrane, the absorbance value of the sample under ultraviolet light was tested and compared with the standard curve, and the loading capacity p (Wt%) of the active ingredient in the liposome composition was calculated as follows:

[0052] Loading amount p = [the amount of active ingredient in the liposome composition Wt / the total amount of active ingredient in the carrier Wz] × 100%

[0053] The encapsulation efficiency of the liposomes was determined by ultrafiltration centrifugation. Specifically, 400uL of the liposome composition was accurately weighed and placed in an ultrafiltration centrifuge tube, and centrifuged at 10000rpm for 30min using a high-speed refrigerated centrifuge; after the centrifugation, the filtrate from the lower layer of the ultrafiltration centrifuge tube was taken and placed in a 10mL volumetric flask, and the content of active ingredients such as the rosewood bark extract or resveratrol or phenylethylresorcinol in the filtrate was determined by HPLC (Wf), and the total content of the active ingredients in the 400uL liposome composition (Wt) was calculated at the same time, and the encapsulation efficiency (EE) was calculated according to the following formula:

[0054] The encapsulation efficiency (EE) was calculated as follows: EE = (Wt-Wf) / Wt*100%.

[0055] The results are shown in the following table.

[0056] Table 2

[0057]

[0058] Table 2'

[0059] Component (wt%) Liposome F Liposome I Liposome J Loading amount p (g / 100g) 19.47 9.48 8.98 Entrapment efficiency (%) 96.44 73.24 64.63

[0060] Example 3: Testing the stability of liposome compositions

[0061] The liposome composition liposomes were placed at room temperature. After one year, it was observed with the naked eye that the control liposomes AC and IM had visible crystal precipitation and obvious stratification, while the color of the liposome DH of the present invention did not change significantly, and no crystal precipitation and stratification were observed.

[0062] Tested by a laser particle size analyzer, the particle sizes of all liposome samples are below 200 nm, within the range of approximately 100 - 120 nm.

[0063] Observed under a cryo-electron microscope, the control liposomes A - C and I - J are basically irregular circles in the field of view, with occasional large irregular elliptical particles; while the particles of the liposomes D - H of the present invention still show regular circles in the initial state; see the attached Figure 1-10 .

[0064] Observed under a microscope, more and larger crystal particles precipitate out from the control liposomes A - C and I - J, and the degree gradually weakens, while no obvious crystal precipitation is observed in the liposomes D - H of the present invention; see the attached Figure 10-20 .

[0065] The technical solutions of the above-described embodiments are the preferred embodiments of the present invention. Without departing from the principle of the present invention, several improvements and transformations can be made, and these improvements and changes should also be regarded as within the protection scope of the present invention.

Claims

1. Use of a combination of sodium stearoyl glutamate and isopropyl lauroylsarcosinate in a liposomal composition comprising a phospholipid emulsifier and an active ingredient, wherein: The content of sodium stearoyl glutamate in the liposomal composition is 0.1 - 3%, the content of isopropyl lauroylsarcosinate in the liposomal composition is 1 - 20%, and the content of the active ingredient in the liposomal composition is more than 5%, based on the total weight of the liposomal composition; and The active ingredient is selected from the group consisting of extract of Ormosia henryi Prain bark, resveratrol, and phenethyl resorcinol.

2. The use according to claim 1, wherein the content of sodium stearoyl glutamate in the liposomal composition is 0.3 - 2%, and the content of isopropyl lauroylsarcosinate in the liposomal composition is 3 - 15%.

3. The use according to claim 2, wherein the content of isopropyl lauroylsarcosinate in the liposomal composition is 5 - 10%.

4. A liposomal composition comprising a phospholipid emulsifier, an active ingredient, sodium stearoyl glutamate, and isopropyl lauroylsarcosinate, wherein: The content of sodium stearoyl glutamate in the liposomal composition is 0.1 - 3%, the content of isopropyl lauroylsarcosinate in the liposomal composition is 1 - 20%, and the content of the active ingredient in the liposomal composition is more than 5%, based on the total weight of the liposomal composition; The active ingredient is selected from the group consisting of extract of Ormosia henryi Prain bark, resveratrol, and phenethyl resorcinol.

5. The liposomal composition according to claim 4, wherein the content of sodium stearoyl glutamate is 0.3 - 2%, and the content of isopropyl lauroylsarcosinate is 3 - 15%.

6. The liposomal composition according to claim 5, wherein the content of isopropyl lauroylsarcosinate in the liposomal composition is 5 - 10%.

7. The liposomal composition according to any one of claims 4 - 6, which comprises 5 - 35% of the active ingredient.

8. The liposomal composition according to claim 7, which comprises 5 - 30% of the active ingredient.

9. The liposomal composition according to claim 8, which comprises 15 - 25% of the active ingredient.

10. The liposomal composition according to any one of claims 4 - 6, wherein the encapsulation efficiency of the active ingredient in the liposomal composition is greater than 70%, based on the total weight of the loaded active ingredient.

11. The liposomal composition according to any one of claims 4 - 6, which has a particle size of 100 - 500 nm.

12. The liposomal composition according to any one of claims 4 - 6, which further comprises a polyol, a membrane modifier, and water.

13. A cosmetic composition comprising the liposomal composition according to any one of claims 4 - 12.

14. The cosmetic composition according to claim 13, wherein the content of the liposomal composition in the cosmetic composition is 3 - 20%, based on the total weight of the cosmetic composition.

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