Preparation of glycolipid liposome and application of glycolipid liposome in cosmetics

Abstract

The invention discloses a glycolipid liposome composition, a preparation method thereof and application of the glycolipid liposome composition in cosmetics. The glycolipid liposome composition comprises glycolipids, lecithin, water, at least one polyol, and at least one active ingredient beneficial to skin; wherein the glycolipids comprise mannosylerythritol lipids, and the mass percent of the mannosylerythritol lipids in the total amount of the glycolipids is at least 60%. The glycolipid liposome composition provided by the invention is simple in preparation process, green, good in stability, good in skin feeling and strong in infiltration capacity, and the efficacy of the prepared cosmetic product is obviously improved.

Description

Technical Field

[0001] The invention relates to the technical field of cosmetic preparation, in particular to the preparation of glycolipid liposome and the application thereof in cosmetics. Background Art

[0002] Nowadays, functional cosmetics, including anti-aging, whitening, acne-removing and other types of cosmetics, are increasingly favored by consumers. Such cosmetics contain active ingredients that are beneficial to the skin, such as retinol, peptides, niacinamide, salicylic acid, etc. Some of these active ingredients can exert their effects on the surface of the skin, such as antifungal or moisturizing ingredients, while some ingredients need to enter the epidermis or even the dermis to exert their effects. Therefore, it is very necessary to develop cosmetic raw material carrier technology that promotes penetration.

[0003] Existing cosmetic penetration enhancement technologies include chemical penetration enhancers, nanoemulsions, microneedles, liposomes, etc. Chemical penetration enhancers such as ethanol and azone may cause certain irritation to the skin when used. Nanoemulsions can promote the penetration of ester actives, but the penetration effect on water-soluble components is not obvious. Microneedles are an efficient and invasive penetration enhancement technology, but there will be obvious tingling and irritation when used. Liposome technology can promote the penetration of both water-soluble and oil-soluble components, but traditional liposomes have complex preparation processes, use of harmful organic solvents, poor stability, wide particle size distribution, unclear penetration enhancement mechanism, and unsatisfactory penetration enhancement effect. These problems need to be improved urgently.

[0004] Glycolipids are very popular ingredients used in cosmetics in recent years. Since they are derived from microbial fermentation, they have the advantages of being natural and green, mild and low-toxic, good biodegradability, and good biocompatibility. Glycolipids can be divided into sophorolipids, rhamnolipids, mannolipids, trehalose lipids, etc., among which the first three have relatively mature production processes. Sophorolipids and rhamnolipids are mainly used in cleaning products, with the effects of cleaning, foaming, and makeup removal. Mannolipids have good skin care effects such as moisturizing, barrier repair, and anti-oxidation, and are very suitable as functional cosmetic raw materials.

[0005] The patent with publication number CN108338356B discloses a chitosan-wrapped mannose erythritol lipid liposome, but it is mainly used in the food field, and the production process is complicated and requires the use of organic solvent chloroform, and its performance in cosmetics cannot be verified. The patent application with publication number CN106174662A discloses a lipid carrier prepared from mannose erythritol lipid, but the organic solvent chloroform is also used in its manufacturing process, and the process is relatively complicated. At present, there are many studies on liposomes in the sample field, but many of them involve injections, and the raw materials used in the cosmetics industry are different from those used in the pharmaceutical industry, and the relevant research on liposomes is not deep enough.

[0006] Some commercially available liposomes have problems such as insufficient natural and green raw materials, complex production processes and the use of a large amount of organic solvents, poor stability, poor skin feel, and unclear penetration-enhancing effects. These problems need to be solved urgently. Therefore, the field urgently needs to develop a green and safe, stable, good skin feel, strong efficacy, and simple preparation process for cosmetic penetration-enhancing raw materials. Summary of the invention

[0007] The invention solves the problems of the existing liposome preparation process being complicated, using organic solvents, and having poor stability, and prepares liposomes which are simple in process, green, have good stability, good skin feel, strong penetration ability, and significantly improved efficacy.

[0008] In a first aspect of the present invention, a glycolipid liposome composition is provided, comprising glycolipids, lecithin, water, at least one polyol, and at least one active ingredient beneficial to the skin; wherein the glycolipids comprise mannitol erythritol lipids, and the mass percentage of mannitol erythritol lipids in the total amount of glycolipids is at least 60%; preferably, at least 65%, 70%, 75%, 80%, 85%, 90%;

[0009] Preferably, the glycolipids do not consist entirely of mannose-erythritol lipids;

[0010] More preferably, the glycolipids further include one or more of sophorolipids, rhamnolipids, and trehalolipids. Preferably, the glycolipids further include sophorolipids and rhamnolipids.

[0011] In one embodiment, the lecithin includes one or more of egg yolk lecithin, soybean lecithin, sunflower lecithin, and hydrogenated products of the aforementioned lecithins;

[0012] Preferably, the lecithin is one or more of the hydrogenated products of egg yolk lecithin, soybean lecithin, and sunflower lecithin;

[0013] Preferably, the mass percentage of the lecithin in the total amount of the glycolipid liposome composition is 0.1-3%; preferably 0.3-1.5%; more preferably 0.4-1%.

[0014] In one embodiment, the mass ratio of the glycolipids to the phosphatidylcholines in the glycolipid liposome composition is 1:100-1:4.

[0015] In one embodiment, the mass fraction of the at least one polyol in the total amount of the glycolipid liposome composition is 1-20%;

[0016] Preferably, the at least one polyol includes one or more of glycerol, propylene glycol, butylene glycol, pentanediol, hexylene glycol, dipropylene glycol, octanediol, and decanediol.

[0017] In one embodiment, the active ingredient beneficial to the skin includes a water-soluble active ingredient and / or an oil-soluble active ingredient;

[0018] Preferably, the water-soluble active ingredient comprises: one or more of niacinamide, panthenol, vitamin C, inositol, adenosine, caffeine, resveratrol, glyceryl glucoside, polypeptide, hyaluronic acid and hydrolyzed collagen;

[0019] Preferably, the oil-soluble active ingredients include: one or more of retinol, vitamin E, ceramide, and linoleic acid.

[0020] In one embodiment, the glycolipid liposome composition may further include a component that is beneficial to the stability of the liposome;

[0021] Preferably, the ingredients that are beneficial to the stability of liposomes include, for example, fatty alcohol, cholesterol, carbomer, and the like.

[0022] In one embodiment, the glycolipid liposome composition comprises: mannitol erythritol lipid 0.01-0.05wt% (preferably 0.01-0.03wt%, more preferably 0.02wt%), sophorolipid 0-0.03wt% (preferably 0-0.02wt%, more preferably 0-0.01wt%), hydrogenated lecithin 0.1-2wt% (preferably 0.2-1.5wt%, more preferably 0.4-1wt%), vitamin E 0-0.2wt% (preferably 0-0.1wt%, more preferably 0-0.05wt%), glycerol 0-5wt% (preferably 0-3wt%, more preferably 0-2wt%), dipropylene glycol 0-20wt% (preferably 0-15wt%, more preferably 0-10wt%), pentylene glycol 1-5wt% (preferably 1-3wt%, more preferably 1-2wt%), hexylene glycol 0-2wt% (preferably 0-1wt%), niacinamide 0-15wt% (preferably 0-10wt%), adenosine 0-0.2wt% (preferably 0-0.1wt%), hyaluronic acid 0-0.1wt% (preferably 0-0.05wt%) and water;

[0023] Preferably, the glycolipid liposome comprises:

[0024] (i) 0.02wt% mannoerythritol lipid, 0.01wt% sophorolipid, 1wt% hydrogenated lecithin, 2wt% glycerol, 2wt% pentylene glycol, 1wt% hexylene glycol, 0.05wt% hyaluronic acid and water;

[0025] (ii) 0.05wt% mannitol erythritol, 0.5wt% hydrogenated lecithin, 2wt% dipropylene glycol, 2wt% pentylene glycol, 1wt% hexylene glycol, 10wt% niacinamide and water; or

[0026] (iii) 0.1 wt% mannoerythritol lipid, 0.4 wt% hydrogenated lecithin, 0.05 wt% vitamin E, 10 wt% dipropylene glycol, 2 wt% pentylene glycol, 0.1 wt% adenosine and water.

[0027] In a second aspect of the present invention, a cosmetic is provided, comprising the glycolipid liposome composition as described in the first aspect of the present invention and a cosmetically acceptable carrier;

[0028] Preferably, the cosmetically acceptable carrier comprises any one or more of a surfactant, a thickener, an emollient, a conditioner, a humectant, a chelating agent, a preservative, an absorbent, a film former, a sunscreen, a pH adjuster and an additive.

[0029] In a third aspect of the present invention, a method for preparing a cosmetic is provided, comprising the steps of: providing the glycolipid liposome composition as described in the first aspect of the present invention, and mixing it with a cosmetically acceptable carrier under appropriate conditions;

[0030] Preferably, the method comprises the steps of:

[0031] 1) adding glycolipids, lecithin and other fat-soluble components in the glycolipid liposome composition to polyol and mixing, and optionally heating to promote dissolution;

[0032] 2) if there is a water-soluble active ingredient, adding the water-soluble active ingredient to water and mixing, optionally heating to promote dissolution; and

[0033] 3) Adding the polyol phase in the glycolipid liposome composition to the aqueous phase under stirring to mix evenly, and then treating with a high-pressure homogenizer for 1-5 times.

[0034] In a fourth aspect of the present invention, provided is the use of the glycolipid liposome composition of the present invention in the preparation of cosmetics.

[0035] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0036] The reagents and raw materials used in the present invention are commercially available.

[0037] The positive and progressive effects of the present invention are:

[0038] 1. Raw materials from natural sources are the development trend of the cosmetics industry. Glycolipid liposomes can be prepared through simple steps to avoid the use of organic solvents.

[0039] 2. By controlling the ratio of glycolipids and lecithin, liposomes with excellent stability and the ability to encapsulate different active substances were obtained.

[0040] 3. Glycolipid liposomes have excellent skin feel, especially easy absorption and skin-friendly feel.

[0041] 4. Compared with traditional liposomes, glycolipid liposomes can significantly improve the penetration effect and amplify the efficacy of cosmetics. The use of confocal Raman in vivo method to test the penetration effect is relatively rare in the industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 The cumulative permeation amount of glycolipid liposomes prepared according to the preparation methods of Example 2 and Comparative Example 3 of the present invention in the in vitro permeation effect test is shown.

[0043] Figure 2 The Raman penetration effect comparison of glycolipid liposomes prepared according to the preparation methods of Example 2 of the present invention and Comparative Example 3 in the in vitro penetration effect test is shown.

[0044] Figure 3 The results show the reduction in melanin content of glycolipid liposomes prepared according to the preparation methods of Example 2 and Comparative Example 3 of the present invention in the evaluation of whitening and freckle removal effects.

[0045] Figure 4 The results show the reduction in the number of spots of the glycolipid liposomes prepared according to the preparation methods of Example 2 and Comparative Example 3 of the present invention in the evaluation of whitening and freckle removal effects.

[0046] Figure 5 The cryo-electron micrograph of glycolipid liposomes prepared according to the preparation method of Example 2 of the present invention is shown. DETAILED DESCRIPTION

[0047] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0048] The following examples and comparative examples provide methods for preparing glycolipid liposomes of different components, wherein the composition and mass percentage of each raw material component are shown in Table 1.

[0049] Table 1

[0050]

[0051] Example 1

[0052] The preparation method of glycolipid liposomes of this embodiment comprises the following steps:

[0053] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 75°C until all dissolved. The components in the water phase were weighed and heated to 75°C, and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed three times using a homogenizer at a pressure of 100 MPa.

[0054] Example 2

[0055] The preparation method of glycolipid liposomes of this embodiment comprises the following steps:

[0056] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 75°C until it was completely dissolved. The components in the water phase were weighed and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed twice using a homogenizer at a pressure of 120 MPa.

[0057] Example 3

[0058] The preparation method of glycolipid liposomes of this embodiment comprises the following steps:

[0059] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 60°C until it was completely dissolved. The components in the water phase were weighed and heated to 80°C, and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed twice using a homogenizer at a pressure of 90 MPa.

[0060] Comparative Example 1

[0061] The preparation method of the glycolipid liposome of this comparative example comprises the following steps:

[0062] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 75°C until all dissolved. The components in the water phase were weighed and heated to 75°C, and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed three times using a homogenizer at a pressure of 100 MPa.

[0063] Comparative Example 2

[0064] The preparation method of the glycolipid liposome of this comparative example comprises the following steps:

[0065] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 75°C until all dissolved. The components in the water phase were weighed and heated to 75°C, and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed three times using a homogenizer at a pressure of 100 MPa.

[0066] Comparative Example 3

[0067] The preparation method of the glycolipid liposome of this comparative example comprises the following steps:

[0068] According to the ingredients and contents in Table 1, the polyol phase was weighed and heated to 75°C until it was completely dissolved. The components in the water phase were weighed and stirred at 2000 rpm for 30 minutes using a high-speed stirrer. The polyol phase was then added to the water phase under stirring to obtain crude liposomes. The crude liposome sample was mixed three times using a homogenizer at a pressure of 100 MPa.

[0069] Performance test 1: Appearance and odor stability

[0070] The samples of the embodiment and the comparative example were placed at 4°C, 25°C, and 45°C for one month to compare the appearance and odor. The stability results are as follows:

[0071] Example 1 has no obvious change under all temperature conditions and has good stability.

[0072] Example 2 has no obvious change at 4°C and 25°C, slightly yellows at 45°C, and has acceptable stability.

[0073] Example 3 has no obvious change at 4°C and 25°C, slightly yellowed at 45°C, and has a slight grease smell, and the stability is acceptable.

[0074] Comparative Example 1 had no significant change at 4°C and 25°C, but had flocculent precipitation at 45°C, and its stability was unqualified.

[0075] Comparative Example 2 had no significant change under all temperature conditions and had good stability.

[0076] Comparative Example 3 had no significant change under all temperature conditions and had good stability.

[0077] Performance Test 2: Particle Size

[0078] The sample was diluted to 10% with pure water and then the particle size was measured using dynamic light scattering. Each sample was repeated 3 times and the results were expressed as mean ± standard deviation. See Table 2. All liposomes had a smaller particle size.

[0079] Table 2 Particle size of examples and comparative examples

[0080]

[0081] Performance test 3: Skin feel evaluation

[0082] The liposomes were made into an essence water sample with a mass fraction of 50%, and the sample was used for skin feel evaluation. The results are as follows:

[0083] Example 1 has a slight slippery feeling, is easily absorbed, adheres to the skin moistly, and has a good overall skin feel.

[0084] Example 2 is easily absorbed and adheres to the skin, with a slight astringent feeling in the later stage, and the overall skin feel is good.

[0085] Example 3 is easily absorbed, adheres to the skin, and has a light feeling on the skin after absorption, with a good overall skin feel.

[0086] Comparative Example 1 is easily absorbed, adheres to the skin, has a moisturizing feel, and has a good overall skin feel.

[0087] Comparative Example 2 is not easily absorbed, and there are many small bubbles when applied. It is difficult to accept this skin feel for a leave-on product.

[0088] Comparative Example 3 is easily absorbed, with a slightly astringent feeling in the later stage, and the overall skin feel is average.

[0089] Performance Test 4: In vitro penetration effect evaluation

[0090] The penetration effect of Example 2 and Comparative Example 3 was tested using the Franz diffusion cell method. The results are shown in Figure 1 As shown, the penetration effect of Example 2 is significantly better than that of Comparative Example 3.

[0091] Performance Test 5: In-body Penetration Evaluation

[0092] Liposomes were prepared into an essence water sample with a mass fraction of 50%, and the penetration effect was studied by Raman spectroscopy of Example 2 and Comparative Example 3 using the confocal Raman method.

[0093] The results are as follows Figure 2 As shown, the penetration effect of Example 2 is significantly better than that of Comparative Example 3.

[0094] Performance test 6: Whitening and freckle removal effect evaluation

[0095] Liposomes were prepared into an essence water sample with a mass fraction of 50%. Example 2 and Comparative Example 3 were used on the left and right faces of 20 subjects, respectively, to compare the melanin content and the number of spots on the facial skin.

[0096] The results are as follows Figure 3 and 4 As shown, the effect of reducing melanin in Example 2 is significantly better than that in Comparative Example 3. Example 2 has a significant effect of reducing the number of spots, while Comparative Example 3 has no effect.

[0097] Performance Test 7: Microstructure

[0098] The microstructure of Example 2 was observed using cryo-electron microscopy. Figure 5 As shown, the structure of the liposome is clearly shown in the figure.

Claims

1. A glycolipid liposome composition, characterized in that: It contains glycolipids, lecithin, water, at least one polyol, and at least one active ingredient beneficial to the skin; Wherein, the glycolipids include mannitol erythritol lipids, and the mass percentage of mannitol erythritol lipids in the total amount of glycolipids is at least 60%.

2. The glycolipid liposome composition according to claim 1, characterized in that The lecithins include one or more of egg yolk lecithin, soybean lecithin, sunflower lecithin, and hydrogenated products of the above lecithins.

3. The glycolipid liposome composition according to claim 1 or 2, characterized in that: The mass ratio of the glycolipids to the phosphatidylcholines in the glycolipid liposome composition is 1:100-1:

4.

4. The glycolipid liposome composition according to any one of claims 1 to 3, characterized in that The mass fraction of the at least one polyol in the total amount of the glycolipid liposome composition is 1-20%.

5. The glycolipid liposome composition according to any one of claims 1 to 4, characterized in that The active ingredients beneficial to the skin include water-soluble active ingredients and / or oil-soluble active ingredients.

6. The glycolipid liposome composition according to any one of claims 1 to 5, characterized in that The glycolipid liposome composition may further include components that are beneficial to the stability of the liposome.

7. The glycolipid liposome composition according to any one of claims 1 to 5, characterized in that The glycolipid liposome composition comprises: 0.01-0.05wt% (preferably 0.01-0.03wt%, more preferably 0.02wt%) of mannitol erythritol, 0-0.03wt% (preferably 0-0.02wt%, more preferably 0-0.01wt%) of sophorolipid, 0.1-2wt% (preferably 0.2-1.5wt%, more preferably 0.4-1wt%) of hydrogenated lecithin, and vitamin E. 0-0.2wt% (preferably 0-0.1wt%, more preferably 0-0.05wt%), glycerol 0-5wt% (preferably 0-3wt%, more preferably 0-2wt%), dipropylene glycol 0-20wt% (preferably 0-15wt%, more preferably 0-10wt%), pentylene glycol 1-5wt% (preferably 1-3wt%, more preferably 1-2wt%), hexylene glycol 0-2wt% (preferably 0-1wt%), niacinamide 0-15wt% (preferably 0-10wt%), adenosine 0-0.2wt% (preferably 0-0.1wt%), hyaluronic acid 0-0.1wt% (preferably 0-0.05wt%) and water.

8. A cosmetic, characterized in that: The invention comprises the glycolipid liposome composition according to any one of claims 1 to 7 and a cosmetically acceptable carrier.

9. A method for preparing cosmetics, characterized in that: The method comprises the steps of providing the glycolipid liposome composition according to any one of claims 1 to 7, and mixing the glycolipid liposome composition with a cosmetically acceptable carrier under appropriate conditions.

10. Use of the glycolipid liposome composition according to any one of claims 1 to 7 in the preparation of cosmetics.

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