Liposome dispersion

Abstract

The present invention addresses a first problem of providing a new liposome dispersion containing thioredoxin. When a saccharomyces / rice fermentation liquid extract that contains thioredoxin is dispersed in an aqueous solvent, turbidity having non-uniform light transmittance occurs therein. The occurrence of turbidity means the precipitation of a component, and potentially leads to a reduction in the pharmaceutical effect of the component. In addition, the occurrence of turbidity potentially leads to a reduction in stability due to uneven aggregation. The present invention addresses a second problem of inhibiting turbidity that occurs when a saccharomyces / rice fermentation liquid extract that contains thioredoxin is dispersed in an aqueous solvent. As a solution to said problems, provided is a liposome dispersion containing thioredoxin or containing a saccharomyces / rice fermentation liquid extract that contains thioredoxin.

Description

Liposome dispersion

[0001] The present invention relates to a liposome dispersion containing thioredoxin and a liposome dispersion containing a Saccharomyces / rice fermentation extract containing thioredoxin.

[0002] It is known that the thermal stability of the higher-order structure (triple helix structure) of collagen is improved by incorporating it into liposomes (Patent Document 1). Thioredoxin is a protein thiol-disulfide oxidoreductase discovered in Escherichia coli in 1964 as a coenzyme for ribonucleotide reductase, which is essential for DNA synthesis, and is ubiquitously found in all living organisms. Thioredoxin is known as an expression promoter for collagen IV, laminin-5, elastin, and fibulin-5 (Patent Document 2). However, it is not known that incorporating thioredoxin into liposomes can suppress the haze that occurs when a Saccharomyces / rice fermentation extract containing thioredoxin is dispersed in water.

[0003] JP 2014-058468 A JP 2016-216436 A

[0004] The first problem to be solved by the present invention is to provide a novel liposome dispersion containing thioredoxin. When a Saccharomyces / rice fermentation extract containing thioredoxin is dispersed in an aqueous solvent, a haze occurs, which causes non-uniform light transmission. The occurrence of the haze indicates precipitation of the components, which may reduce the efficacy of the components. Furthermore, the occurrence of the haze may lead to reduced stability due to non-uniform aggregation. The second problem to be solved by the present invention is to suppress the occurrence of the haze when a Saccharomyces / rice fermentation extract containing thioredoxin is dispersed in an aqueous solvent.

[0005] The main features of the present invention are as follows: 1. A liposome dispersion containing thioredoxin. 2. A liposome dispersion containing 0.0001% by mass or more and 0.004% by mass or less of thioredoxin. 3. A liposome dispersion obtained by adding thioredoxin to a dispersion for liposome preparation and subjecting the dispersion to a high-pressure dispersion treatment. 4. A method for producing a liposome dispersion by adding thioredoxin to a dispersion for liposome preparation and subjecting the dispersion to a high-pressure dispersion treatment. 5. A method for producing a cosmetic by adding thioredoxin to a dispersion for liposome preparation and subjecting the dispersion to a high-pressure dispersion treatment, and mixing the liposome dispersion produced by adding thioredoxin to the dispersion for liposome preparation and subjecting the dispersion to a high-pressure dispersion treatment. 6. A cosmetic containing the liposome dispersion described in any one of 1. to 3. 7. A liposome dispersion containing a Saccharomyces / rice fermentation extract containing thioredoxin. 8. A liposome dispersion containing 0.05% by mass or more and 2% by mass or less of a Saccharomyces / rice fermentation extract containing thioredoxin. 9. A liposome dispersion obtained by adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for liposome preparation and subjecting the resulting dispersion to a high-pressure dispersion treatment. 10. A method for producing a liposome dispersion by adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for liposome preparation and subjecting the resulting dispersion to a high-pressure dispersion treatment. 11. A method for producing a cosmetic by adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for liposome preparation and subjecting the resulting dispersion to a high-pressure dispersion treatment, and mixing the resulting dispersion with a liposome dispersion produced by adding a Saccharomyces / rice fermentation extract containing thioredoxin to the dispersion for liposome preparation. 12. A cosmetic containing the liposome dispersion according to any of 7. to 9.

[0006] We have been able to provide a liposome dispersion containing thioredoxin. It is expected that liposomal formation will improve the skin penetration of thioredoxin and extend the duration of its effects. We have been able to uniformly disperse a Saccharomyces / rice fermentation extract containing thioredoxin in an aqueous solvent. By uniformly dispersing a Saccharomyces / rice fermentation extract containing thioredoxin in an aqueous solvent, we are able to prevent precipitation of the ingredients and prevent a decrease in the efficacy of the ingredients. Furthermore, by preventing the generation of haze, we are able to prevent a decrease in stability.

[0007] The liposome dispersion of the present invention contains thioredoxin or a Saccharomyces / rice fermentation extract containing thioredoxin.

[0008] Thioredoxin, Saccharomyces / Rice Fermentation Extract Containing Thioredoxin The thioredoxin used in the present invention may be a commercially available purified product used as a reagent, or may be an animal or plant extract, or an extract of bacteria, fungi, algae, or the like containing thioredoxin, or may be a human recombinant protein. Thioredoxin, a human recombinant protein, is a recombinant peptide produced using E. coli called human oligopeptide-4, and commercially available products include "recombinant human thioredoxin" manufactured by Oriental Yeast Co., Ltd. and "rhuTRX" manufactured by Arista Health and Nutrition Science, Inc. The amount of thioredoxin incorporated into the liposome dispersion of the present invention is preferably 0.0001% by mass or more and 0.004% by mass or less.

[0009] The thioredoxin-containing Saccharomyces / rice fermentation extract used in the present invention can be a commercially available raw material with the cosmetic labeling name "Saccharomyces / rice fermentation extract." Saccharomyces / rice fermentation extract is an extract obtained by alcoholic fermentation of rice with yeast of the genus Saccharomyces. The thioredoxin concentration can be increased by concentrating the Saccharomyces / rice fermentation extract by ultrafiltration. The commercially available sake extract "Bioredoxil" manufactured by Arista Health and Nutrition Science, Inc. can be used as the thioredoxin-containing Saccharomyces / rice fermentation extract. The amount of thioredoxin-containing Saccharomyces / rice fermentation extract incorporated in the liposome dispersion of the present invention is preferably 0.05% by mass or more and 2% by mass or less.

[0010] Liposome dispersion: Liposomes are capsule structures consisting of a single or multiple layers of a lipid bilayer membrane made of phospholipids. Phospholipid molecules are shaped like pine needles and possess two properties: the phosphate portion is hydrophilic and the fatty acid ester portion is hydrophobic. When placed in water, the hydrophobic portion assembles inward, while the hydrophilic portion faces outward, forming a lipid bilayer membrane and forming a spherical liposome. Liposomes can encapsulate water-soluble medicinal ingredients in their hydrophilic portion and oil-soluble medicinal ingredients in their hydrophobic portion. Liposomes are typically approximately 100-300 nm (0.1-0.3 μm) in size. Because they are nano-sized particles, liposomes are known to enhance skin penetration and sustained efficacy of ingredients held within them. Furthermore, due to their pleasant texture, they are widely used in topical skin preparations to improve their effectiveness and ease of use.

[0011] The liposome dispersion of the present invention can be prepared using a high-pressure emulsifier. Phospholipids and sterols are dissolved in a polyhydric alcohol, heated to 60 to 95°C, and coarsely emulsified using a homomixer while adding water. Next, an aqueous dispersion of thioredoxin or a Saccharomyces / rice fermentation extract containing thioredoxin is added to the coarse emulsion, and the mixture is dispersed under high pressure using a high-pressure emulsifier to prepare a liposome dispersion containing thioredoxin or a Saccharomyces / rice fermentation extract containing thioredoxin. Examples of high-pressure emulsifiers that can be used include a wet media-less micronizer (NanoVeita) manufactured by Yoshida Kikai Kogyo Co., Ltd., a thin film rotation-type high-speed homomixer (T.K. Filmix) manufactured by Primix Corporation, an ultra-high-pressure homogenizer (Microfluidizer) manufactured by Microfluidics, and an internal shear force mixer (Clearmix) manufactured by M-Technique Co., Ltd.

[0012] The phospholipid used in the present invention is preferably a natural lecithin purified and the phosphatidylcholine content adjusted to 55 to 95% by mass, in order to prepare stable, minute liposomes. Commercially available phospholipids can be used, such as Resinol S-10M and Resinol S-10M Plus manufactured by Nikko Chemicals, and Phospholipon 90G manufactured by H-Holstein. The phospholipid concentration when preparing the liposome dispersion of the present invention is preferably 0.1 to 10% by mass. A concentration of 1 to 2% by mass is particularly preferred to prepare a stable liposome dispersion.

[0013] Sterols used in the present invention include animal sterols, plant sterols (phytosterols), fungal sterols, etc. Examples of animal sterols include cholesterol, cholestanol, and 7-dehydrocholesterol. Examples of plant sterols (phytosterols) include sitosterol, stigmasterol, fucosterol, spinasterol, and brassicasterol. Examples of phytosterols include phytostanol, which is a hydrogenated product of a plant sterol. Examples of fungal sterols include ergosterol. Commercially available sterols can be used, such as Phytosterol-S manufactured by Tama Biochemical Co., Ltd., Cholesterol manufactured by Nippon Fine Chemical Co., Ltd., and CHOLESTEROL NF manufactured by Croda Co., Ltd.

[0014] Examples of the polyhydric alcohol used in the present invention include glycerin, 1,3-butylene glycol, dipropylene glycol, propylene glycol, isoprene glycol, and 1,2-pentanediol.

[0015] When preparing a liposome dispersion containing the thioredoxin of the present invention or the Saccharomyces / rice fermentation extract containing thioredoxin, it is possible to add a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, an oil, a moisturizer, a water-soluble polymer, an antioxidant, an ultraviolet absorber, a chelating agent, a preservative, an antibacterial agent, a colorant, a fragrance, or the like.

[0016] By high-pressure dispersion treatment, at least a portion of thioredoxin or Saccharomyces / rice fermentation extract containing thioredoxin is incorporated into the internal phase of liposomes. That is, liposomes produced by high-pressure dispersion treatment contain thioredoxin or Saccharomyces / rice fermentation extract containing thioredoxin in their internal phase. Note that, because liposomes are nano-sized capsules made of lipid bilayer membranes, there are some circumstances that make it impossible or impractical to analyze the presence of thioredoxin or Saccharomyces / rice fermentation extract containing thioredoxin in the internal phase of liposomes.

[0017] The formulation of a cosmetic containing the liposome dispersion of the present invention may be any of an aqueous solution (meaning an aqueous solution in which liposomes are dispersed), an oil-in-water emulsion composition, a water-in-oil emulsion composition, a multiple emulsion composition, and a multilayer agent. Cosmetics containing the liposome dispersion of the present invention can be lotions, emulsions, creams, beauty serums, packs, hair growth agents, sunscreen cosmetics, liquid foundations, hair treatments, hair rinses, etc. The liposome dispersion containing the Saccharomyces / rice fermentation extract containing thioredoxin of the present invention does not produce haze and is stable, making it particularly suitable for incorporation into liquid lotions and beauty serums.

[0018] In order to incorporate the liposome dispersion of the present invention into a cosmetic product containing the liposome dispersion of the present invention, it is desirable to stir and mix the liposome dispersion in the final step of cosmetic production at 70° C. or below, preferably at 20 to 30° C. If the liposome dispersion is mixed at a temperature above about 70° C., the liposomes may be destroyed.

[0019] Liposome dispersions of Examples 1 and 2 and Comparative Examples 1 to 6 were prepared according to the formulations in Table 1.

[0020]

[0021] "Method for producing a Saccharomyces / rice fermentation extract containing thioredoxin" Rice was subjected to alcoholic fermentation using a yeast belonging to the genus Saccharomyces, concentrated by ultrafiltration, and the residue was freeze-dried and pulverized. The thioredoxin content of the obtained Saccharomyces / rice fermentation extract was 0.2% by mass.

[0022] "Method for preparing liposome dispersions in Examples 1 and 2" Hydrogenated lecithin and phytosterols were dissolved in glycerin and BG at 80 to 85°C, and coarsely emulsified using a homomixer while adding water. After coarse emulsification, the mixture was cooled, and an aqueous dispersion of Saccharomyces / rice fermentation extract (in a hazy state due to non-uniform light transmittance) was added to prepare a dispersion for liposome preparation. This dispersion for liposome preparation was dispersed under high pressure using a micronizer (NanoVeita, manufactured by Yoshida Kikai Kogyo) to prepare a liposome dispersion containing Saccharomyces / rice fermentation extract containing thioredoxin. "Method for preparing dispersions in Comparative Examples 1 to 6" The components shown in the table were mixed, stirred using a homomixer at 80 to 85°C, and then cooled to prepare a dispersion.

[0023] "Method for checking for haze" The dispersion immediately after preparation was placed in a glass bottle with a diameter of 3.2 cm, and the occurrence of haze (non-uniform light transmittance) was confirmed visually.

[0024] "Results" The results are shown in Table 1. No haze was generated in the liposome dispersions of Examples 1 and 2, and the haze that occurs when a Saccharomyces / rice fermentation extract containing thioredoxin is dispersed in an aqueous solvent was successfully suppressed. In Comparative Examples 1 to 6, an attempt was made to suppress the haze by using PEG-hydrogenated castor oil, which is commonly used as a surfactant for solubilization, but the light transmittance was non-uniform and the haze could not be eliminated.

Claims

1. Thioredoxin-containing liposome dispersion.

2. A liposome dispersion containing 0.0001% by mass or more and 0.004% by mass or less of thioredoxin.

3. A liposome dispersion obtained by adding thioredoxin to a dispersion for preparing liposomes and subjecting the dispersion to high-pressure dispersion treatment.

4. A method for producing a liposome dispersion, which comprises adding thioredoxin to a dispersion for liposome preparation and subjecting the dispersion to high-pressure dispersion treatment.

5. A method for producing a cosmetic preparation by incorporating thioredoxin into a dispersion for preparing liposomes, and then mixing the resulting dispersion with a liposome dispersion liquid produced by subjecting the dispersion to high-pressure dispersion treatment.

6. A cosmetic preparation containing the liposome dispersion liquid described in any one of claims 1 to 3.

7. A liposome dispersion containing a Saccharomyces / rice fermentation extract containing thioredoxin.

8. A liposome dispersion containing 0.05% by mass or more and 2% by mass or less of a Saccharomyces / rice fermentation extract containing thioredoxin.

9. A liposome dispersion obtained by adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for preparing liposomes and subjecting the dispersion to high-pressure dispersion treatment.

10. A method for producing a liposome dispersion, which comprises adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for preparing liposomes, and then subjecting the dispersion to a high-pressure dispersion treatment.

11. A method for producing a cosmetic product by adding a Saccharomyces / rice fermentation extract containing thioredoxin to a dispersion for preparing liposomes, and then mixing the resulting dispersion with a liposome dispersion produced by high-pressure dispersion treatment.

12. A cosmetic preparation containing the liposome dispersion liquid described in any one of claims 7 to 9.

Images