Liposomes and liposome-containing topical skin preparations

Abstract

The objective was to provide liposomes that can be stably incorporated into topical skin preparations, and topical skin preparations containing such liposomes. [Solution] Liposomes containing ceramides, phospholipids, and phytosterols; and topical skin preparations containing such liposomes.

Description

Technical Field

[0001] The present invention relates to ceramides, liposomes containing phospholipids and phytosterols, and external skin preparations containing such liposomes.

Background Art

[0002] Liposomes are closed vesicles composed of lipid bilayers and are used as model systems for biological membranes and carriers for various drugs. However, liposomes are easily affected by light, heat, temperature, osmotic pressure, etc., and are likely to undergo chemical or physical changes. There were problems such as aggregation and fusion of liposome particles with each other in solution, and further generation of precipitates and precipitation of insoluble substances, resulting in state changes and functional degradation. Therefore, various developments have been made regarding the stability of liposomes. Cosmetics (Patent Document 1) in which the stability of liposomes and the dispersibility of pigments are improved by containing a specific pigment mixture and a liposome dispersion, a liposome-containing composition (Patent Document 2) that can be stably formulated in cosmetics by suppressing the leakage of water-soluble bioactive substances encapsulated in liposomes, liposomes containing phospholipids and sterols (Patent Document 3), etc. have been developed.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, topical skin preparations containing liposomes have stability issues, and when incorporated into topical skin preparations, the liquid crystal structure tends to break down over time. Therefore, the present invention aims to provide liposomes that can be stably incorporated into topical skin preparations, and topical skin preparations containing such liposomes. [Means for solving the problem]

[0005] The present invention provides liposomes containing ceramides, phospholipids, and phytosterols, as well as a topical skin preparation containing these liposomes. [Effects of the Invention]

[0006] The liposomes of the present invention exhibit the effect of efficiently forming a multilayered lamellar structure. Furthermore, topical skin preparations containing the liposomes of the present invention exhibit excellent stability over time. [Modes for carrying out the invention]

[0007] The following describes embodiments for carrying out the present invention.

[0008] Liposomes are closed vesicles composed of lipid bilayers and can usually be prepared by hydrating lipids, primarily phospholipids, with a sufficient amount of water. Liposomes are generally classified based on the number of lipid bilayers, into multilayer liposomes and monolayer liposomes. While any of these can be used, multilayer liposomes are preferred in this invention.

[0009] The liposomes of the present invention contain ceramides, phospholipids, and phytosterols.

[0010] (Ceramides) The ceramides used in this invention are human-type ceramides and their acylated derivatives. Examples of such ceramides include ceramide NDS (ceramide 10), ceramide ADS (ceramide 11), ceramide ODS, ceramide EODS, ceramide NS (ceramide 2), ceramide AS (ceramide 5), ceramide OS, ceramide EOS (ceramide 1), ceramide NP (ceramide 3), ceramide AP (ceramide 6), ceramide OP, ceramide EOP (ceramide 9), ceramide NH (ceramide 8), ceramide AH (ceramide 7), ceramide OH, ceramide EOH (ceramide 4), ceramide NSD, ceramide ASD, ceramide OSD, and ceramide EOSD. Furthermore, examples of acylated products include 1-O-acylceramide NP, particularly 1-O-stearic acid ceramide NP, which is obtained by introducing a long-chain acyl group with 14 to 24 carbon atoms into ceramide NP.

[0011] (phospholipids) The phospholipids used in the liposomes in the present invention are lipids having a phosphate ester moiety in their molecular structure, and specifically include phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and phosphatidic acid. Among these, phosphatidylcholine and phosphatidylethanolamine are preferred from the viewpoint of the stability of the liposome composition, and phosphatidylcholine is more preferred. Specifically, a mixture of the above phospholipids, whose composition differs depending on their origin, can be used, and is not particularly limited as long as it is used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., and examples include soybean-derived phospholipids, soybean-derived hydrogenated phospholipids, soybean-derived lysophospholipids, soybean-derived hydrogenated lysophospholipids, egg yolk-derived phospholipids, egg yolk-derived hydrogenated phospholipids, egg yolk-derived lysophospholipids, and egg yolk-derived hydrogenated lysophospholipids, and one or more of these can be used as needed. Specifically, commercially available products such as NIKKOL Lesinol S-10E (manufactured by Nikko Chemicals Co., Ltd.), Basis LS-60HR (manufactured by Nisshin Oillio Group Co., Ltd.), Egg Yolk Lecithin PL-100P (manufactured by Kewpie Corporation), and HSL-70 (manufactured by YMC Co., Ltd.) can be used.

[0012] (Phytosterols) The phytosterols used in the liposomes of this invention are a type of sterol, but are components found in trace amounts in plants such as soybeans and rapeseed, and are a mixture of several sterols such as β-sitosterol, campesterol, stigmasterol, and brassicasterol. Phytosterols contribute to the stability of the lipid bilayer structure, and when combined with phospholipids, they can improve the storage stability of liposomes. Commercially available products include phytosterol QI, phytosterol QIF (both manufactured by Mitsubishi Chemical Corporation), and phytosterol-S (manufactured by Tama Biochemical Co., Ltd.).

[0013] In the present invention, a premix raw material of phospholipids and phytosterols can also be used. Examples of such raw materials include phytopresome, phytocompo PP, and primelipid PI (all manufactured by Nippon Seika Co., Ltd.).

[0014] Liposomes can be obtained by conventional methods. For example, phospholipids and sterols can be dissolved in a small amount of BG, then dispersed in an aqueous solution or buffer solution for pre-emulsification, and finally dispersed under high pressure to form a lipid bilayer, thereby obtaining a liposome dispersion.

[0015] The size (outer diameter) of the liposomes incorporated into the topical skin preparation of the present invention is 10 to 1000 nm, preferably 30 to 600 nm, and more preferably 50 to 400 nm.

[0016] The liposomes of the present invention can be incorporated into topical skin preparations.

[0017] The dosage form of the topical skin preparation used in the present invention is not particularly limited and may be any dosage form, such as aqueous or emulsified.

[0018] In addition to the above components, the topical skin preparation used in the present invention can contain optional components commonly used in ordinary cosmetics and quasi-drugs, as long as the effects of the present invention are not inhibited. Specifically, examples thereof include oils, surfactants, thickeners, preservatives, fragrances, moisturizers, antioxidants, anti-inflammatory agents, antibacterial agents, and the like.

[0019] The topical skin preparation used in the present invention can be prepared by a conventional method.

Examples

[0020] Hereinafter, the present invention will be specifically described by way of examples, but the scope of the present invention is not limited thereby.

[0021] Liposomes were prepared according to the formulation shown in Table 1. (Preparation method) 1: Heat the A phase to 70°C and disperse it uniformly. 2: Add 1 to the B phase heated to 70°C while stirring with a homomixer at 2000 rpm. 3: After further stirring with a homomixer at 3000 rpm for 5 minutes, add the C phase.

[0022]

Table 1

[0023] (Small-angle X-ray scattering (SAXS) measurement of liposomes) The obtained liposomes were encapsulated in a solution cell to prepare a measurement sample (Sample 1). Separately, a BG aqueous solution containing no liposomes was prepared as a control measurement sample (Sample 2) in the same manner. SAXS measurements were performed on Sample 1 and Sample 2 under the conditions of detector: imaging plate (IP), measurement time: 5 minutes, and measurement temperature: 25°C using BLG19B2 at Spring-8. The obtained scattering profiles were analyzed, and the number of liposome lamellar layers and the lamellar formation rate were evaluated as follows. ◎: Sufficient multilayer lamellae are formed, and the lamellar formation rate is very good ○: Multilayer lamellae are formed, and the lamellar formation rate is good. △: Insufficient formation of multilayer lamellae and lamellar formation rate.

[0024] Next, we will show an example of a formulation of a topical skin preparation containing the liposomes of the present invention.

[0025] (Examples 10-11) Liposome-containing topical skin preparations were prepared using the formulations shown in Table 2. In Examples 10 and 11, TEM observation confirmed that liposomes remained stable even after 1 month at 50°C following preparation. ·Preparation method 1: Heat phase A to 70°C and disperse it uniformly. 2. Add 1 to phase B, which has been heated to 70°C, while stirring with a homomixer at 2000 rpm. 3. Further mix with a homomixer at 3000 rpm for 5 minutes to prepare liposomes. 4. Add liposomes to the homogenized C phase and mix.

[0026] [Table 2]

[0027] (Examples 12-13) Liposome-containing topical skin preparations were prepared using the formulations shown in Table 3. In the topical skin preparations of Examples 12 and 13, TEM observation confirmed that liposomes remained stable even after 1 month at 50°C following preparation. ·Preparation method 1: Heat phase A to 70°C and disperse it uniformly. 2. Add 1 to phase B, which has been heated to 70°C, while stirring with a homomixer at 2000 rpm. 3. Further mix with a homomixer at 3000 rpm for 5 minutes to prepare liposomes. 4. Add phase C to the homogenized phase D and emulsify, then add liposomes and mix.

[0028] [Table 3]

Claims

1. Liposomes containing ceramides, phospholipids, and phytosterols.

2. A topical skin preparation containing liposomes as described in claim 1.

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