topical skin preparations

Abstract

To provide an external preparation for skin in which liposomes are stably incorporated.SOLUTION: An external preparation for skin comprises following (A) and (B): (A) liposomes containing phospholipids and sterols; and (B) one or two more selected from polyoxyethylene phytosteryl ether and polyglyceryl fatty acid ester.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an external skin preparation that stably contains liposomes. [Background technology]

[0002] Liposomes are closed endoplasmic reticulum composed of lipid bilayers and are used as model systems for biological membranes and as carriers for various drugs. However, liposomes are susceptible to light, heat, temperature, osmotic pressure, and other factors, and are prone to chemical and physical changes. Problems include aggregation and fusion of liposome particles in solution, as well as the formation of precipitates and precipitation of insoluble matter, which can lead to changes in state and reduced functionality. For this reason, various developments have been made to improve liposome stability. Examples include cosmetics containing a specific pigment mixture and liposome dispersion to improve liposome stability and pigment dispersibility (Patent Document 1), and liposome-containing compositions that can be stably incorporated into cosmetics by suppressing leakage of water-soluble physiologically active substances encapsulated in liposomes (Patent Document 2). However, issues remain regarding the stable incorporation of liposomes. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-269720 [Patent Document 2] Japanese Patent Application Laid-Open No. 2012-72065 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide an external skin preparation that stably contains liposomes. [Means for solving the problem]

[0005] The present invention provides an external skin preparation containing the following (A) and (B): (A) Liposomes containing phospholipids and sterols (B) one or more selected from polyoxyethylene phytosteryl ether and polyglycerin fatty acid ester [Effects of the Invention]

[0006] The present invention can provide an external skin preparation that stably incorporates liposomes. [Brief explanation of the drawings]

[0007] [Figure 1] FIG. 1 is a graph showing the rate of change in transmitted light (T) intensity measured at 50° C. using a Turbiscan liquid dispersion stability evaluation device.

[0008] [Figure 2] FIG. 2 is a graph showing the rate of change in transmitted light (T) intensity measured at 55° C. using a Turbiscan liquid dispersion stability evaluation device. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, an embodiment of the present invention will be described.

[0010] Liposomes are closed endoplasmic reticulum consisting of lipid bilayers, and can be prepared by hydrating lipids, usually phospholipids, with a sufficient amount of water. Liposomes are generally classified based on the number of lipid bilayers, and are divided into multilamellar liposomes and unilamellar liposomes. Either of these can be used, but multilamellar liposomes are preferred in the present invention.

[0011] The liposomes incorporated into the topical skin preparation of the present invention contain phospholipids and sterols. The form in which the phospholipids and sterols are contained in the liposomes is not particularly limited. For example, they may be present in a hydrophilic or hydrophobic region formed inside the liposome, or may be attached to the outermost membrane of the liposome, but are preferably membrane components of the liposome.

[0012] [Phospholipids] The phospholipid contained in the liposomes incorporated into the topical skin preparation of the present invention can be any phospholipid commonly used in topical skin preparations. Specific examples include phosphatidylcholine (also called lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, and hydrogenated versions of these. Among these, hydrogenated lecithin is preferably used.

[0013] The amount of the phospholipid in the present invention is preferably 0.00005 to 1% by mass, more preferably 0.0005 to 1% by mass, based on the total amount of the external skin preparation.

[0014] [Sterols] The sterols contained in the liposomes incorporated into the topical skin preparation of the present invention have a sterol skeleton in their structure, and any sterols commonly used in topical skin preparations can be used. Specific examples include cholesterol, phytosterols, and lanosterol. Among these, phytosterols are preferably used.

[0015] The blending amount of the sterols in the present invention is preferably 0.00001 to 1% by mass, more preferably 0.0001 to 0.5% by mass, based on the total amount of the external skin preparation.

[0016] The liposomes to be incorporated into the topical skin preparation of the present invention can be obtained by a conventional method. For example, a liposome dispersion can be obtained by dissolving phospholipids and sterols in a small amount of BG, dispersing the resulting solution in an aqueous solution or buffer solution, pre-emulsifying the solution, and then dispersing the solution under high pressure to form a lipid bilayer.

[0017] The size (outer diameter) of the liposomes incorporated into the external skin preparation of the present invention is 10 to 1000 nm, preferably 30 to 600 nm, and more preferably 50 to 400 nm.

[0018] The liposomes incorporated into the topical skin preparation of the present invention can also contain various lipophilic or hydrophilic components in the lipid membrane and the internal aqueous phase, respectively. Examples of lipophilic components that can be contained in the lipid membrane include vegetable oils or vegetable waxes such as avocado oil, almond oil, olive oil, sesame oil, camellia oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, and jojoba oil; isopropyl myristate, isopropyl palmitate, hexyl laurate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl 2-ethylhexanoate, glyceryl tri-2-ethylhexanoate, Ester oils such as trimethylolpropane trioctanoate, sphingolipids such as ceramide, glycosphingolipids, and sphingophospholipids, hydrophobic amino acids such as phenylalanine, tryptophan, isoleucine, leucine, proline, methionine, valine, and alanine, and their lipophilic derivatives, vitamins A such as retinol, retinal, and retinoic acid, and their lipophilic derivatives, provitamin A such as α-carotene, β-carotene, and γ-carotene, cholecalciferol, ergocalciferol Lipophilic vitamins such as vitamin D and their lipophilic derivatives, 7-dehydrocholesterol, ergosterol, and other provitamin D and their lipophilic derivatives, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, and other vitamin E and their lipophilic derivatives, phylloquinone, menaquinone, menadione, and other vitamin K and their lipophilic derivatives, ubiquinone and its lipophilic derivatives, lipoic acid and its lipophilic derivatives, linoleic acid and its lipophilic derivatives lipophilic vitamin-like action factors such as linolenic acid and its lipophilic derivatives, arachidonic acid and its lipophilic derivatives, etc.; lipophilic derivatives of water-soluble vitamins such as riboflavin butyrate, pyridoxine dicaprylate, pyridoxine dipalmitate, ascorbyl palmitate, ascorbyl dipalmitate, etc.; lipophilic anti-inflammatory agents such as guaiazulene, ethyl guaiazulenesulfonate, stearyl glycyrrhetinate, etc., and one or more of these may be selected and used.

[0019] Examples of hydrophilic components to be encapsulated in the internal aqueous phase include polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, glycerin, etc.; monosaccharides and oligosaccharides such as glucose, galactose, fructose, saccharose, maltose, etc.; sugar alcohols such as inositol, sorbitol, maltitol, etc.; hydrophilic amino acids such as lysine, glutamine, asparagine, glutamic acid, aspartic acid, threonine, arginine, serine, pyrrolidone carboxylic acid, etc., and their salts and hydrophilic derivatives; vitamin B1s such as thiamine, their salts and hydrophilic derivatives; vitamin B2s such as riboflavin, their salts and hydrophilic derivatives; niacins such as nicotinic acid and nicotinamide, their salts and hydrophilic derivatives; vitamin B6s such as pyridoxine, pyridoxal, pyridoxamine, etc., and their salts and hydrophilic derivatives; pantothenic acid, its salts and hydrophilic derivatives; biotin, its salts and hydrophilic derivatives; folic acid, its salts and hydrophilic derivatives; orotic acid and its salts and hydrophilic derivatives; carnitine and its salts and hydrophilic derivatives; hydrophilic vitamin-like factors such as vitamin P such as hesperidin, eriodictin, and rutin; 2-hydroxycarboxylic acids such as glycolic acid, lactic acid, and citric acid and their salts and hydrophilic derivatives; mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, dermatan sulfate, and heparin and their salts and hydrophilic derivatives; peptides such as soluble collagen, collagen hydrolysate, elastin hydrolysate, and keratin hydrolysate and their salts and hydrophilically modified products; hydrophilic anti-inflammatory agents such as allantoin and its salts and hydrophilic derivatives, guaiazulene sulfonate, and glycyrrhizic acid and its salts and hydrophilic derivatives; and plant extracts using polar solvents. One or more of these can be selected and used.

[0020] [Polyoxyethylene phytosteryl ether] The polyoxyethylene phytosteryl ether to be incorporated into the external skin preparation of the present invention may be one that is usually incorporated into external skin preparations.

[0021] Examples of polyoxyethylene phytosteryl ethers include PEG-5 phytosterol (HLB value: 7), PEG-10 phytosterol (HLB value: 9), PEG-20 phytosterol (HLB value: 12), PEG-25 phytosterol (HLB value: 13), and PEG-30 phytosterol (HLB value: 18 Among these, it is preferable to use PEG-30 phytosterol.

[0022] Commercially available PEG-30 phytosterol products include Nikkol BPS-30 (manufactured by Nikko Surfactant Kogyo Co., Ltd.).

[0023] [Polyglycerol fatty acid ester] The polyglycerol fatty acid ester to be incorporated into the external skin preparation of the present invention may be one that is usually incorporated into external skin preparations.

[0024] Examples of polyglycerin fatty acid esters include polyglyceryl-10 isostearate (HLB value: 14), polyglyceryl-2 isostearate (HLB value: 5), polyglyceryl-4 isostearate (HLB value: 8), polyglyceryl-6 isostearate (HLB value: 11), polyglyceryl-10 oleate (HLB value: 13), polyglyceryl-2 oleate (HLB value: 6), polyglyceryl-4 oleate (HLB value: 9), polyglyceryl-6 oleate (HLB value: 12), polyglyceryl-2 caprylate (HLB value: 8), polyglyceryl-6 caprylate (HLB value: 10), polyglyceryl-10 diisostearate (HLB value: 11), dioleic acid Examples include polyglyceryl-10 (HLB value: 12), polyglyceryl-6 dicaprate (HLB value: 10), polyglyceryl-10 distearate (HLB value: 12), polyglyceryl-10 stearate (HLB value: 14), polyglyceryl-2 stearate (HLB value: 5), polyglyceryl-4 stearate (HLB value: 6), polyglyceryl-2 sesquicaprylate (HLB value: 8), polyglyceryl-10 tristearate (HLB value: 8), polyglyceryl-10 myristate (HLB value: 15), polyglyceryl-4 laurate (HLB value: 10), polyglyceryl-6 laurate (HLB value: 14), and polyglyceryl-10 laurate (HLB value: 14.8). Among these, polyglyceryl-10 laurate is preferably used.

[0025] Commercially available products of polyglyceryl-10 laurate include Ryoto Polyglycerol L-7D (manufactured by Mitsubishi Chemical Corporation), Decaglin 1-L (manufactured by Nippon Surfactant Industry Co., Ltd.), S-Face L-1001, SY Glystar ML-750, S-Face 10G-L (all manufactured by Sakamoto Pharmaceutical Industry Co., Ltd.), Sunsoft M-12J, Sunsoft M-12JW, Sunsoft Q-12S-C, Sunsoft Q-12Y-C, Sunsoft M-122Y (all manufactured by Taiyo Kagaku Co., Ltd.), and polyglycerin fatty acid ester ML10 (manufactured by Daicel Corporation).

[0026] In the present invention, the blend amount of one or more selected from polyoxyethylene phytosteryl ether and polyglycerin fatty acid ester is preferably 0.01 to 5 mass %, more preferably 0.01 to 3 mass %, based on the total amount of the external skin preparation.

[0027] In addition to the above-mentioned components, the topical skin preparation of the present invention may contain optional components used in ordinary cosmetics and quasi-drugs to the extent that the effects of the present invention are not impaired. Specific examples of such components include ultraviolet absorbers, ultraviolet scattering agents, oils, surfactants, thickeners, preservatives, fragrances, pigments, moisturizers, antioxidants, anti-inflammatory agents, and antibacterial agents.

[0028] The formulation of the external skin preparation of the present invention is not particularly limited, and may be any of aqueous, oil-based, emulsion-type, and the like.

[0029] The topical skin preparation of the present invention can be prepared by a conventional method. [Example]

[0030] The present invention will be described in more detail below with reference to examples, but the scope of the present invention is not limited thereto. In the following examples, the blending amounts are expressed in mass % unless otherwise specified.

[0031] [Stability evaluation] Skin topical preparations according to the examples and comparative examples were prepared, and measurements were carried out using a Turbiscan Tower (manufactured by Sanyo Trading Co., Ltd.) as a liquid dispersion stability evaluation device to evaluate the stability of the liposomes over time.

[0032] [Measurement method] The topical skin preparations according to the Examples and Comparative Examples were placed in a Turbiscan glass bottle and left at room temperature for 1 hour, after which 20 ml of each was sampled using a dropper. The sample in the glass bottle was then irradiated with 850-880 nm light, and the intensity of the backscattered light was measured. The light irradiation range was from the bottom of the glass bottle to a height that included the entire meniscus of the sample liquid; in this case, measurements were taken up to 40 mm. The transmitted light (T) intensity was measured using a detector at a position 180 degrees from the incident angle of the light. The first measurement was taken immediately after sample introduction, and subsequent measurements were taken at 2-minute intervals for 4 hours. The temperature inside the device had to be adjusted to the target temperature beforehand, and measurements were carried out at 50°C and 55°C. The first measurement value at each temperature was compared with the second and subsequent measurements to calculate the rate of change in transmitted light intensity, and the following evaluation was carried out.

[0033] [Evaluation criteria] 50℃ Stable absolute value of 0.15% or less: Yes Absolute value of 0.16% or more is unstable: × 55℃ Stable absolute value of 0.35% or less: Yes Absolute value of 0.36% or more is unstable: ×

[0034] [Presence or absence of aggregates] The topical skin preparations according to the Examples and Comparative Examples were prepared, left to stand at 40°C or 50°C for one month, and then left to stand at room temperature for four months. Three expert evaluators independently visually checked for the presence or absence of aggregates, and then conducted the following evaluation by consensus.

[0035] [Evaluation criteria] No agglomerates: 〇 Aggregates present: ×

[0036] For the topical skin preparation having the formulation shown in Table 1, hydrogenated lecithin, phytosterols, BG, glycerin, and purified water were mixed in advance to prepare a liposome dispersion (part I in Table 1) using a conventional method. Separately, the other ingredients were uniformly mixed using a conventional method to prepare a composition, to which the liposome dispersion was added and homogenized, thereby preparing the topical skin preparation.

[0037] [Table 1]

[0038] As shown in Table 1, the results of Turbiscan measurements of the topical skin preparation of the present invention showed that the liposomes had good stability over time, and no aggregates were observed visually. Therefore, the topical skin preparation of the present invention can stably incorporate liposomes.

Claims

1. A topical skin preparation containing the following (A) and (B): (A) A liposome containing a phospholipid and a sterol, wherein the phospholipid is 0.00005 to 0.9% by mass relative to the total amount of the topical skin preparation, and the sterol is 0.00001 to 1% by mass relative to the total amount of the topical skin preparation, and the size (outer diameter) of the liposome is 50 to 400 nm. (B) PEG-30 phytosterol, which is 0.5 to 5% by mass of the total amount of the topical skin preparation.

2. 2. The external skin preparation according to claim 1, wherein (A) is a liposome obtained using a phospholipid, a sterol, 1,3-butylene glycol, and water.

3. The external skin preparation according to claim 1 or 2, wherein in (A), the phospholipid comprises hydrogenated lecithin.

4. The external skin preparation according to claim 1 or 2, wherein in (A), the liposome comprises a multilayer liposome.

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