Liposome dispersion, and cosmetics and topical skin preparations containing liposome dispersion

Abstract

To provide a liposome dispersion that is excellent in preservation efficacy against microbial contamination and long-term storageability, and a topical preparation for skin containing the liposome dispersion.SOLUTION: A liposome dispersion contains a liposome containing (A) water, (B) hydrogenated lecithin, (C) butyleneglycol, (D) hydrolyzed collagen, and (E) pentyleneglycol. There are also provided cosmetics and topical preparations for skin containing the liposome dispersion.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a liposome dispersion, and a cosmetic and an external skin preparation containing this liposome dispersion. [Background technology]

[0002] A liposome is a capsule structure consisting of a single or multiple layers of a lipid bilayer membrane made of phospholipids. Phospholipid molecules are shaped like pine needles and have two properties: the phosphate portion is hydrophilic and the fatty acid ester portion is hydrophobic. When released into water, the hydrophobic portion gathers inside and the hydrophilic portion faces outward, forming a lipid bilayer membrane and forming a spherical liposome. Liposomes can confine water-soluble medicinal ingredients in their hydrophilic portions and oil-soluble medicinal ingredients in their hydrophobic portions. Liposomes are generally about 100-300 nm (0.1-0.3 μm) in size, and because they are nano-sized particles, they are known to improve the skin permeability of ingredients held in them. Because they also have an excellent texture, they are widely used in topical skin preparations to improve their effectiveness and ease of use.

[0003] On the other hand, liposome raw materials are generally known to be susceptible to microbial contamination and to be difficult to store stably for long periods of time. Therefore, liposome raw materials are generally formulated with preservatives. For example, Patent Document 1 proposes a liposome preparation that contains a combination of sorbic acid and salicylic acid or their water-soluble salts, and has excellent preservative effectiveness against microbial contamination. However, the sorbic acid and salicylic acid used in Patent Document 1 are undesirable in terms of skin irritation. Furthermore, even if other preservatives are substituted, a certain number of consumers currently have allergic reactions or aversion to preservatives, so the incorporation of preservatives is not considered desirable. Patent Document 2 proposes a composition containing liposomes containing a hydrophobic alkanediol. However, there is a concern that the hydrophobic portion of the hydrophobic alkanediol may be incorporated into the lipid bilayer membrane of the liposome over time, thereby impairing the stability of the liposome itself. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Special Publication No. 2003-535030 [Patent Document 2] Japanese Patent Application Laid-Open No. 2012-072065 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention addresses the problem of providing a liposome dispersion that has excellent preservative effect against microorganisms and long-term storage stability, and a cosmetic preparation and an external skin preparation that contain this liposome dispersion. [Means for solving the problem]

[0006] The present invention relates to a liposome dispersion characterized by containing liposomes containing (A) water, (B) hydrogenated lecithin, (C) butylene glycol, and (D) hydrolyzed collagen, and (E) pentylene glycol, as well as to a cosmetic composition and a topical skin preparation containing this liposome dispersion.

[0007] (A) Water is the dispersion medium, and (C) butylene glycol acts as a solvent for (B) hydrogenated lecithin. (E) Pentylene glycol is an ingredient with antibacterial properties. In conventional technology, when pentylene glycol was added to a liposome dispersion, the particle size of the liposomes changed over time, with the particle size changing by more than 20% after two months of storage at 40°C, eventually causing the liposomes themselves to break down.

[0008] The liposomes of the present invention contain (A) water, (B) hydrogenated lecithin, (C) butylene glycol, and (D) hydrolyzed collagen. This prevents the liposome particles from being destabilized by (E) pentylene glycol, which is added to the dispersion to enhance preservative effectiveness (preservative properties). This prevents the liposome particles from being destabilized (which changes particle size over time and eventually leads to breakage). This results in the liposome dispersion of the present invention having excellent storage stability. In the present invention, the storage stability of liposomes is determined by the rate of change in liposome particle size. Specifically, liposomes with a small rate of change in particle size (all changes in particle size before and after storage are within ±20%) have good storage stability because the liposomes themselves are not broken down.

[0009] The liposome dispersion of the present invention has excellent storage stability due to two aspects: the liposomes themselves do not break down, and their preservative effect (antiseptic properties) is high. The liposome dispersion of the present invention can be stocked for long periods as a raw material for cosmetics and topical skin preparations, and the complicated production of liposome dispersions can be carried out in bulk, making it a useful technology that can reduce production costs. Cosmetics and topical skin preparations containing the liposome dispersion of the present invention are safe for the skin and have an excellent feel when used. Furthermore, the liposome dispersion of the present invention can be provided as is as cosmetics and topical skin preparations that are non-irritating and have a good feel when used.

[0010] The main means for solving the problems of the present invention are as follows. 1. A liposome dispersion comprising liposomes containing (A) water, (B) hydrogenated lecithin, (C) butylene glycol, and (D) hydrolyzed collagen, and (E) pentylene glycol. 2. The liposome dispersion according to 1., characterized in that the component (E) is contained in an amount of 2.5% by mass or more relative to 100% by mass of the liposome dispersion. 3. The liposome dispersion according to 1. or 2., wherein the mass ratio of component (B) to component (D) is within the range of 1:0.2 to 1:1.1. 4. A cosmetic or topical skin preparation containing a liposome dispersion satisfying any one of 1. to 3.

[0011] 5. A storage stabilizer for liposome dispersions containing hydrolyzed collagen as an active ingredient and containing a polyhydric alcohol having 5 or more carbon atoms. [Effects of the Invention]

[0012] The liposome dispersion of the present invention has excellent preservative effect against microorganisms, and the liposomes undergo little change even after long-term storage, demonstrating excellent storage stability. The liposome dispersion of the present invention has excellent antimicrobial preservative properties even without substantial incorporation of an antimicrobial agent, and can be stored for long periods of time, allowing it to be stockpiled, for example, as a raw material for cosmetics. Conventional liposomes and liposome dispersions are susceptible to the influence of their formulations, making them unsuitable for long-term storage from the standpoints of preservative properties and particle stability. This means that liposome dispersions must be prepared each time a final cosmetic or topical skin preparation is produced. However, the liposome dispersion of the present invention can be stockpiled, eliminating the need for frequent, complicated manufacturing processes and making it suitable for use in cosmetics and topical skin preparations. The liposome dispersion of the present invention has enhanced antimicrobial preservative properties due to the antimicrobial polyhydric alcohol. Furthermore, because it is a so-called preservative-free liposome dispersion with high storage stability, in which instability of the liposome dispersion, such as changes in liposome particle size, is suppressed, cosmetics and topical skin preparations containing it naturally have excellent skin safety. The cosmetic and topical skin preparation of the present invention have moisturizing properties and a good feel when used. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a graph showing the change in particle size of the liposome dispersion of Example 1 before and after storage for two months. [Figure 2] FIG. 1 is a graph showing the change in particle size of the liposome dispersion of Comparative Example 1 before and after storage for two months. DETAILED DESCRIPTION OF THE INVENTION

[0014] "Liposome dispersion" The liposome dispersion of the present invention contains liposomes containing (A) water, (B) hydrogenated lecithin, (C) butylene glycol, (D) hydrolyzed collagen, and (E) pentylene glycol.

[0015] Liposomes The liposome of the present invention contains (A) water, (B) hydrogenated lecithin, (C) butylene glycol, and (D) hydrolyzed collagen. (A) Water Water is the main medium of the liposome dispersion, and purified water, deionized water, pure water, etc. The water content is preferably 50% by mass or more, and more preferably 70% by mass or more, relative to 100% by mass of the entire liposome dispersion of the present invention.

[0016] (B) Hydrogenated lecithin Hydrogenated lecithin is a phospholipid and is the main component of the lipid bilayer membrane of liposomes. Examples of hydrogenated lecithin include hydrogenated lecithin, which is obtained by converting part or all of the unsaturated carbon chains in natural lecithin, such as egg yolk lecithin or soybean lecithin, into saturated bonds through hydrogenation, and hydrogenated synthetic phosphatidylcholine. Hydrogenated lecithin can be used alone or in combination of two or more types. Among these, hydrogenated soybean lecithin derived from soybean lecithin is preferred. The blending amount of hydrogenated lecithin is preferably 0.01% by mass or more and 5% by mass or less, and more preferably 0.1% by mass or more and 3% by mass or less, relative to 100% by mass of the liposome dispersion of the present invention.

[0017] Commercially available hydrogenated lecithin products include Resinol S-10M (phosphatidylcholine content 55 to 65%) and Resinol S-10E (phosphatidylcholine content 75 to 85%) manufactured by Nikko Chemicals Co., Ltd., Basis LP-60HR (phosphatidylcholine content 65 to 75%) manufactured by Nisshin Oillio Co., Ltd., COATSOME NC-61 (phosphatidylcholine content 60% or more) manufactured by Nippon Oil & Fats Corporation, and egg yolk lecithin PL100P (phosphatidylcholine content approximately 80%) manufactured by Kewpie Corporation. Furthermore, other phospholipids such as non-hydrogenated lecithin, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, and phosphatidylglycerol can also be used in combination, as long as the effects of the present invention are not impaired. For example, other phospholipids can be used in an amount of 10% by mass or less relative to 100% by mass of hydrogenated lecithin.

[0018] (C) Butylene Glycol Butylene glycol is used as a solvent for (B) hydrogenated lecithin when preparing a liposome dispersion. The content of butylene glycol is preferably 2% by mass or more and 8% by mass or less, and more preferably 3% by mass or more and 7% by mass or less, relative to 1% by mass of (B) hydrogenated lecithin, since this facilitates the preparation of the liposome dispersion.

[0019] (D) Hydrolyzed collagen Hydrolyzed collagen improves the storage stability of the liposome dispersion of the present invention containing pentylene glycol. Hydrolyzed collagen can improve storage stability by preventing instability of the liposome dispersion caused by polyhydric alcohols with 5 or more carbon atoms, such as pentylene glycol, such as changes in liposome particle size. Hydrolyzed collagen acts as a liposome storage stabilizer in the presence of polyhydric alcohols with 5 or more carbon atoms, such as pentylene glycol, which destabilize liposomes, and therefore its inclusion is essential. Examples of polyhydric alcohols with 5 or more carbon atoms that destabilize liposomes during long-term storage include pentylene glycol, octanediol, and hexanediol. Liposome destabilization refers to a change in the average liposome particle size measured before and after two months of storage at 5, 25, or 40°C, with any of the changes exceeding ±20%. Note that, in this specification, particle size refers to the median diameter, which can be measured by known methods, such as dynamic light scattering. By including hydrolyzed collagen, even if a component that destabilizes liposomes is included, the particle size of the liposomes changes over time, and it is possible to prevent the liposomes from breaking down over time.

[0020] Hydrolyzed collagen is a hydrolyzate of collagen or gelatin. The hydrolyzed collagen of the present invention can be any type commonly used in cosmetics, and its origin can be, for example, from animals such as pigs, cows, and birds, as well as fish, shellfish, jellyfish, and sponges. However, from the standpoints of odor, productivity, and cost, collagen derived from marine organisms is preferred. The hydrolysis method is not particularly limited, and may be hydrolysis with a hydrolases, hydrolysis with an acid or alkali, or hydrolysis by microbial fermentation. The hydrolyzed collagen used in the present invention preferably has a low molecular weight, specifically, a weight-average molecular weight of 400 to 1200. Furthermore, the hydrolyzed collagen used in the present invention preferably contains 20% by mass or more of tripeptides. Examples of commercially available products include CTP-F60 (weight average molecular weight 500, tripeptide content ≧55%), CTP-F (weight average molecular weight 1000, tripeptide content ≧25%), CTP-S (weight average molecular weight 1000, tripeptide content ≧25%), and CTP-M30 (weight average molecular weight 1000, tripeptide content ≧25%), all manufactured by Jellice.

[0021] From the viewpoint of storage stability of the liposome dispersion, the content of hydrolyzed collagen is preferably 0.2 to 1.1 parts by mass, and more preferably 0.3 to 1 part by mass, per part by mass of (B) hydrogenated lecithin. That is, the mass ratio of component (B) to component (D) is preferably 1:0.2 to 1:1.1, and more preferably 1:0.3 to 1:1. Furthermore, the hydrolyzed collagen preferably contains 20% by mass or more of tripeptides, more preferably 30% by mass or more, and even more preferably 50% by mass or more. By containing a high proportion of tripeptides, it is expected that the hydrolyzed collagen will promote collagen synthesis and hyaluronic acid production when used as a cosmetic or topical skin preparation.

[0022] (E) Pentylene glycol Pentylene glycol improves the preservative effectiveness of the liposome dispersion of the present invention against microorganisms. In the present invention, a good preservative effectiveness is determined when it meets the criteria set forth in Criteria A of the ISO preservative standard for bacteria and yeasts, and when the number of bacteria does not exceed the initial number after 28 days for mold. As will be described in detail below, pentylene glycol is added after liposome formation. Water-soluble components are generally distributed relatively freely between the inside and outside of liposomes, but since the liposome dispersion of the present invention exhibits excellent preservative effectiveness, most of the pentylene glycol is added as an external phase component of the liposomes. From the viewpoint of preservative effectiveness against microorganisms, the content of pentylene glycol is preferably 2.5% by mass or more, more preferably 3% by mass or more, relative to 100% by mass of the liposome dispersion of the present invention. The upper limit of the content may be within the range in which the effects of the present invention are exhibited, and is, for example, about 10% by mass or less, relative to 100% by mass of the liposome dispersion.

[0023] The liposomes used in the present invention contain the above-described components (A) to (D). The liposomes of the present invention are sufficient as long as they contain these components (A) to (D), and can also contain other components to the extent that the effects of the present invention are not impaired. Examples of other components include hydrophilic or lipophilic medicinal ingredients contained in the internal phase of the liposome or between the lipid bilayer membrane, externally responsive compounds that impart temperature or pH responsiveness to the liposome, and sterols or copolymers that form part of the lipid bilayer membrane. Other examples include water-soluble organic solvents such as ethanol, various aqueous or oily active ingredients, vitamins, cosmetic ingredients, whitening agents, emollients, moisturizers, chelating agents, antioxidants, UV absorbers, pH adjusters, colorants, and fragrances (including essential oils).

[0024] "Method of manufacturing liposome dispersion" The liposome dispersion of the present invention can be prepared, for example, as follows. First, (B) hydrogenated lecithin and (C) butylene glycol are heated to 60-95°C and uniformly dissolved. Separately, (D) hydrolyzed collagen and (A) water are heated to 60-95°C and uniformly mixed. The heating temperature is preferably 80°C or higher, and more preferably 85°C or higher. On the other hand, if the heating temperature is too high, the components may be oxidized or thermally denatured, the time and cost required for heating may increase, and (A) water may evaporate, changing the composition ratio. Therefore, the heating temperature is preferably 90°C or lower.

[0025] The solutions of (D) and (A) are added dropwise to a mixture of (B) and (C) while stirring, and then processed using a high-pressure micronizer or the like to prepare liposomes. The size of the liposomes can be adjusted by the magnitude of the shear force applied using the high-pressure micronizer. The size of the liposomes is not particularly limited, but since smaller liposomes are better absorbed into the skin, the average particle size measured by dynamic light scattering is preferably 200 nm or less, and more preferably 150 nm or less. After processing, it is preferable to quickly cool the liposomes to approximately 30°C using an ice bath or the like to prevent morphological changes. Furthermore, by incorporating an active ingredient or the like into the liquid prior to liposome formation, the active ingredient or the like can be incorporated into the internal phase of the liposomes and the interior of the lipid bilayer membrane. Finally, (E) pentylene glycol (pentanediol) is added to obtain the liposome dispersion of the present invention.

[0026] "Cosmetics, topical skin preparations" The cosmetic and topical skin preparation of the present invention contain the liposome dispersion described above. This liposome dispersion is substantially free of so-called antibacterial agents (preservatives) such as parabens, and contains a polyhydric alcohol (pentylene glycol) with antibacterial properties, thereby providing excellent preservative effectiveness against microorganisms. Furthermore, the liposome particle size change rate is small, meaning the liposomes do not change shape or break down, allowing for long-term storage. Therefore, by preparing the liposome dispersion in advance and storing it at room temperature, it can be stored in the same manner as various cosmetic ingredients typically stored at room temperature. When preparing cosmetics or topical skin preparations, it can be used as a raw material without the need for the cumbersome process of repeatedly producing liposomes. Because the cosmetic and topical skin preparation of the present invention do not contain preservatives such as parabens derived from liposome raw materials, they are highly safe for the skin and provide an excellent feel when used. Note that, as used herein, "preservative-free" means that they are not intentionally added, and does not exclude preservatives that may be originally included in a mixture formulated for the purpose of imparting a certain effect. The liposome dispersion can also be provided as it is as a cosmetic or topical skin preparation.

[0027] The topical skin preparation of the present invention includes cosmetics, quasi-drugs, and pharmaceuticals, and can be in the form of a solution, emulsion, or polymer gel preparation such as a lotion, emulsion, cream, or gel. It can also be a foam preparation, multilayer preparation, spray preparation, a sheet impregnated into a nonwoven fabric, or a gel pack preparation. The prepared liposome dispersion can be used as a topical skin preparation directly, or the liposome dispersion can be incorporated into a moisturizing topical skin preparation such as a lotion, emulsion, cream, or gel. The topical skin preparation of the present invention can be in the form of an aqueous solution, an oil-in-water emulsion composition, a water-in-oil emulsion composition, a multiple emulsion composition, or a multilayer preparation.

[0028] The topical skin preparation of the present invention may contain other ingredients used in cosmetics, quasi-drugs, and pharmaceuticals depending on its intended use. Examples of such other ingredients include water-soluble organic solvents such as ethanol, various aqueous or oily active ingredients, vitamins, cosmetic ingredients, whitening agents, emollients, moisturizers, chelating agents, antioxidants, UV absorbers, pH adjusters, coloring agents, and fragrances (including essential oils), which may be incorporated within a range that does not impair the effects of the present invention. [Example]

[0029] The present invention will be described in detail below based on examples, but the present invention is not limited to these. The units of compositions in the tables are % by mass.

[0030] Using some or all of the following ingredients and purified water, liposome dispersions of Test Examples 1 to 3, Examples 1 and 2, and Comparative Example 1 were prepared. The liposome dispersions can be used as they are as cosmetics or topical skin preparations. (B) Hydrogenated lecithin "Recinol S-10M Plus" manufactured by Nippon Surfactant Industries Co., Ltd. (C) 1,3-butylene glycol (BG) manufactured by Daicel Corporation (D) Hydrolyzed collagen "CTP-F60" manufactured by Jellice Ectoin "RonaCare Ectoin" manufactured by Merck (E) Pentylene glycol manufactured by Kokyu Alcohol Kogyo Co., Ltd.

[0031] "Evaluation Method" -Preservative effect against microorganisms Tests of preservative effectiveness against microorganisms were conducted according to the method specified by ISO. Specifically, if the test met the criteria for bacteria and yeast as specified in Criteria A of the ISO preservative standard, and if the number of bacteria did not exceed the initial number after 28 days as for mold, it was judged to have good preservative effectiveness and was marked with a circle, and if not, it was marked with an X. ·Storage stability The evaluation was based on the average particle size of the liposome dispersion. The particle size of the liposomes was measured by dynamic light scattering using a particle size distribution analyzer ("ELSZ-1000" manufactured by Otsuka Electronics Co., Ltd.) After storage at 5, 25, and 40°C for 2 months, the particle size of the liposomes was measured in the same manner and evaluated according to the following criteria. ○: The change in particle size before and after storage is within ±20% in all cases. ×: The particle size change before and after storage exceeds ±20%

[0032] "Test 1: (E) Pentylene glycol blend amount study" (B) Hydrogenated lecithin and (C) butylene glycol were weighed out and uniformly dissolved at 85°C in the compositions of Test Examples 1 to 3 shown in Table 1. (A) Water heated to 85°C was added dropwise to this composition while stirring, and then the mixture was processed using a homomixer (Primix Corporation, Homomixer MARK II, 6000 rpm) to prepare liposomes. The mixture was then rapidly cooled to 30°C using an ice bath. The particle size was then adjusted using a high-pressure micronizer (Yoshida Kikai Kogyo Co., Ltd., NanoVater). (E) Pentylene glycol was added to obtain a liposome dispersion. The results are shown in Table 1.

[0033] [Table 1]

[0034] ·result (E) By adding 3% by mass of pentylene glycol, the preservative effect against microorganisms was improved. However, the storage stability was insufficient in all cases.

[0035] "Test 2: (C) Formulation of hydrolyzed collagen" In the compositions of Examples 1 and 2 and Comparative Example 1 shown in Table 2, (B) hydrogenated lecithin and (C) butylene glycol were weighed out and uniformly dissolved at 85°C. (D) hydrolyzed collagen and (A) water were heated to 85°C and mixed uniformly. The solutions (B) and (C) were added dropwise to a mixture of (D) and (A) while stirring, and then processed using a homomixer (Primix Corporation, Homomixer MARK II, 6000 rpm) to prepare liposomes. The mixture was then quickly cooled to 30°C in an ice bath. The particle size was then adjusted using a high-pressure micronizer (Yoshida Kikai Kogyo Co., Ltd., NanoVater). (E) Pentylene glycol was added to obtain a liposome dispersion. The results are shown in Table 2. The particle size changes in Example 1 and Comparative Example 1 are shown in Figures 1 and 2, respectively.

[0036] [Table 2]

[0037] ·result The liposome dispersions obtained in Examples 1 and 2 of the present invention were excellent in storage stability and preservative effect against microorganisms. (D) Example 2, which contained both hydrolyzed collagen and ectoin, also had excellent storage stability and preservative effect against microorganisms, and was able to maintain storage stability even when an active ingredient such as ectoin was added. Both the liposome dispersions of Examples 1 and 2 could be provided as lotions that were pleasant to use and did not irritate the skin. (C) The liposome dispersion obtained in Comparative Example 1, which contained only ectoine (cyclic amino acid) instead of hydrolyzed collagen, had excellent preservative effect against microorganisms, but after storage at 40°C for 2 months, the liposome particle size increased by more than five times, indicating poor storage stability.

Claims

1. (A) water, (B) hydrogenated lecithin, (C) butylene glycol, (D) liposomes containing hydrolyzed collagen, and (E) pentylene glycol, A liposome dispersion characterized in that the mass ratio of component (B) to component (D) is 1:0.2 to 1:1.1, and the liposome dispersion contains 2.5% by mass or more and 10% by mass or less of component (E) relative to 100% by mass of the liposome dispersion.

2. A cosmetic or topical skin preparation comprising the liposome dispersion according to claim 1.

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