Application of gamma-oryzanol and application of liposome containing gamma-oryzanol
阅读说明：本技术 γ-谷维素的用途与内包有γ-谷维素的脂质体的用途 (Application of gamma-oryzanol and application of liposome containing gamma-oryzanol ) 是由 平野晶子 木下雅崇 福永丈朗 米田早织 后藤昌史 于 2019-04-24 设计创作，主要内容包括：本发明提供一种γ-谷维素的用途与内包有γ-谷维素的脂质体的用途,用于有效率地获得抗皮肤老化效果的方法。本发明是一种含有γ-谷维素(优选内包有γ-谷维素的脂质体)的抗皮肤老化外用组合物。(The invention provides an application of gamma-oryzanol and an application of liposome containing the gamma-oryzanol, and a method for efficiently obtaining an anti-skin aging effect. The present invention is an anti-skin aging external composition containing gamma-oryzanol (preferably liposome internally containing gamma-oryzanol).)
1. Use of gamma-oryzanol for the manufacture of a composition for external use for combating skin ageing.
2. Use of gamma-oryzanol for the manufacture of a topical composition for inhibiting the production of reactive oxygen species in the skin and/or inhibiting the production of matrix metalloproteinase-1.
3. Use of a liposome encapsulating gamma-oryzanol for the manufacture of a composition for external use for combating skin aging.
4. Use of a liposome containing gamma-oryzanol for producing an external composition for inhibiting the production of matrix metalloproteinase-2 and/or inhibiting the production of matrix metalloproteinase-9 in the skin.
5. The use according to claim 1 or 3, wherein,
skin aging is wrinkling or sagging.
6. The use according to claim 1 or 3, wherein,
skin aging is skin aging caused by light.
7. The use according to claim 1 or 3, wherein,
the composition for external use is a cosmetic composition.
Technical Field
The present invention relates to the use of gamma-oryzanol and the use of liposomes containing gamma-oryzanol.
Background
In recent years, particularly in the field of cosmetics, there has been an increasing demand for compositions for external use that exhibit an anti-skin aging effect. Among them, the concern of suppressing wrinkles or sagging of the skin is very high.
One of the causes of wrinkles or sagging in the skin is irradiation of the skin with light (Ultraviolet light, particularly, long-wave Ultraviolet light (UVA)). Ultraviolet rays (particularly UVA) in light reach the dermis, and are thought to damage tissues and cause skin aging (for example, thickening of the epidermis, formation of deep and large wrinkles, or sagging) through the generation of Reactive Oxygen Species (ROS) (non-patent document 1). Therefore, it is expected that a component having an antioxidant effect in the skin suppresses the generation of ROS, thereby suppressing skin aging.
In addition, the breakdown and reduction of dermal elastic or collagen fibers is associated with skin photoaging. Matrix Metalloproteases (MMPs) are known to be involved in the degradation of dermal structural components, and in particular, MMPs-1, MMP-2, and MMP-9 degrade type IV collagen, which forms a basement membrane, or elastin, type I collagen, and type III collagen, which form the dermis. MMP decomposes dermal collagen and a basement membrane, and the skin structure becomes unable to be maintained, whereby the skin largely dents to form deep wrinkles. In particular, it is also considered that MMP-2 or MMP-9 is derived from keratinocytes (keratinocyte) or fibroblasts (fibroplast) by UV irradiation or ROS exposure (non-patent document 1). In addition, the following report is also available: MMP-1 is highly active in both naturally aged skin and photoaged skin, and is highly active in photoaged skin in particular (non-patent document 2). Therefore, among the components that inhibit the generation of ROS, components that can also inhibit MMP derivatives are expected to be particularly effective for combating skin aging.
Disclosure of Invention
Problems to be solved by the invention
The present invention addresses the problem of providing a method for efficiently obtaining an anti-skin-aging effect.
Means for solving the problems
The present inventors have found that γ -oryzanol (oryzanol) is an excellent anti-skin aging material that can exhibit not only an effect of inhibiting ROS production but also an effect of inhibiting MMP derivative, and have found that when γ -oryzanol is encapsulated in a liposome (liposome), a more excellent anti-skin aging effect can be obtained, and have repeated improvements, thereby completing the present invention.
The present invention includes, for example, the subject matters described in the following items.
An anti-skin aging external composition comprises gamma-oryzanol.
The composition according to
Item 3.
An anti-skin aging external composition comprises liposome containing gamma-oryzanol.
Item 4.
The composition according to item 3, which is used for inhibiting the production of matrix metalloproteinase-2 (MMP-2) and/or for inhibiting the production of matrix metalloproteinase-9 (MMP-9).
The composition according to
The composition according to any one of
The composition according to any one of
ADVANTAGEOUS EFFECTS OF INVENTION
The present invention provides a composition for external use which has an excellent anti-skin aging effect.
Drawings
Fig. 1 shows the results of evaluating the effect on the generation of Reactive Oxygen Species (ROS) generated when fibroblasts are irradiated with ultraviolet light (UVA) with respect to gamma-oryzanol.
FIG. 2 shows the results of evaluating the effect of gamma-oryzanol on MMP-1 production when fibroblasts are irradiated with Ultraviolet (UVA) light.
FIG. 3 shows the results of analysis of the changes in the expression levels of antioxidant genes (Nuclear Factor Erythroid 2-related Factor 2(Nuclear Factor Erythroid
Fig. 4 shows the results of real-time PCR analysis of how the expression level of antioxidant genes (Nrf2 and Nqo1) was changed by liposomes containing γ -oryzanol.
Detailed Description
Hereinafter, embodiments of the present invention will be described in more detail.
The anti-skin aging composition contained in the present invention is an external composition containing γ -oryzanol (preferably, an external composition containing liposomes in which γ -oryzanol is encapsulated). Hereinafter, the composition may be referred to as an anti-skin aging external composition of the present invention.
Liposomes are lipid vesicles having a bilayer membrane formed by hydrating lipids mainly composed of phospholipids with a large amount of water. Liposomes are classified according to the number of lipid molecular membrane layers, and specifically, are classified into multi-membrane liposomes (Multilamellar vesicles, MLV) and Unilamellar liposomes (Unilamellar vesicles, ULV). In addition, Unilamellar liposomes may be further classified according to the size of lipid vesicles, and specifically, they are classified into Small Unilamellar Vesicles (SUV), Large Unilamellar Vesicles (LUV), and Giant Unilamellar Vesicles (GUV) in order from Small to Large. In the present invention, the liposome may be any of them. MLV is preferred. In the present invention, the size of the liposome is not particularly limited, but the average particle diameter is, for example, preferably 30nm to 1000nm, more preferably 30nm to 600nm, and still more preferably 50nm to 300 nm.
In the composition for external use containing a liposome in which γ -oryzanol is encapsulated, the amount of γ -oryzanol encapsulated in the liposome is not particularly limited, but is exemplified by about 0.2 to 3 parts by mass, about 0.5 to 2 parts by mass, or about 1 to 1.5 parts by mass, relative to 10 parts by mass of a liposome membrane component (preferably, phospholipid contained in the liposome).
In the anti-skin aging external composition of the present invention, it is preferable that the composition contains, for example, about 0.001 to 5% by mass, about 0.005 to 4.5% by mass, about 0.01 to 4% by mass, about 0.02 to 2.5% by mass, about 0.05 to 1% by mass, or about 0.05 to 0.5% by mass of γ -oryzanol. Further, for example, it is also preferable to contain about 0.001 to 0.01% by mass of γ -oryzanol, and particularly when γ -oryzanol is contained in a state of not being encapsulated in a liposome, it is preferable to contain about 0.001 to 0.01% by mass.
When the composition is a composition for external use containing a liposome in which γ -oryzanol is entrapped, the content of γ -oryzanol entrapped in the liposome is preferably, for example, about 0.01 to 5% by mass, about 0.02 to 2.5% by mass, about 0.05 to 1% by mass, or about 0.05 to 0.5% by mass, based on the composition. In addition, the γ -oryzanol contained in the composition is preferably contained in a liposome containing γ -oryzanol, for example, in an amount of 80 to 100% by mass, 90 to 100% by mass, or substantially 100% by mass. In addition, the fact that substantially 100% by mass of the γ -oryzanol contained in the composition is contained in the liposome in which γ -oryzanol is encapsulated means that when the composition is produced so that all γ -oryzanol is encapsulated in the liposome, the γ -oryzanol inevitably exists also outside the liposome.
As a method for including γ -oryzanol in liposomes, a well-known method or a method which can be easily conceived according to a well-known method can be used, and it is usually obtained as a state in which liposomes are dispersed in an aqueous solution, that is, a liposome suspension. The method for producing the liposome suspension is not particularly limited, and examples thereof include the following methods. (1) A method of forming liposomes by homogeneously mixing phospholipids, a component (including oryzanol; the same applies hereinafter) included in liposomes, and other antioxidants as necessary, and then hydrating the mixture (the hydration is preferably carried out using an aqueous solution containing a pH adjuster, a polyhydric alcohol, a saccharide, and the like). (2) A method for producing liposomes by dissolving phospholipids, components encapsulated in liposomes, and other antioxidants as needed in an alcohol, a polyol, or the like, and hydrating the solution with an aqueous solution containing a pH adjuster, a polyol, a saccharide, or the like. (3) A method of preparing liposomes by complexing phospholipids, components encapsulated in liposomes, and optionally other antioxidants in water using ultrasonic waves, a french press (french press) or a homogenizer. (4) A method in which phospholipids, a component encapsulated in liposomes, and optionally other antioxidants are mixed and dissolved in ethanol, and the ethanol solution is added to an aqueous potassium chloride solution, followed by removal of the ethanol to prepare liposomes. The γ -oryzanol may be used as it is, or may be dissolved in a small amount of a solvent (for example, water or an aqueous solvent) before use.
The phospholipid to be used is not particularly limited, but is exemplified by: soybean lecithin, rapeseed lecithin, corn lecithin, cottonseed oil lecithin, sunflower lecithin, egg yolk lecithin, protein lecithin, peanut lecithin, and the like. Lecithin, also known as phosphatidylcholine or 1, 2-diacylglycerol-3-phosphocholine, is typically bound with fatty acids at the 1 and 2 positions of glycerol. In the present invention, for example, lecithin in which an unsaturated fatty acid having 12 to 24 carbon atoms is bonded to both or either of the 1-position and the 2-position is preferably used, and lecithin in which a saturated fatty acid having 12 to 24 carbon atoms is bonded to the 1-position and an unsaturated fatty acid having 12 to 24 carbon atoms is bonded to the 2-position is more preferably used. Here, the saturated fatty acid and the unsaturated fatty acid may be either linear or branched. In addition, a lecithin derivative may be used instead of or in addition to lecithin. Examples of the lecithin derivative include: hydrogenated lecithin, or a compound obtained by introducing polyethylene glycol, an aminopolysaccharide, or the like into the phospholipid in the above-mentioned exemplary lecithin. Among them, preferred are soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin, and particularly preferred are soybean lecithin and egg yolk lecithin. Further, purified lecithin having an improved purity of phospholipids (e.g., phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, sphingomyelin (sphingomyelin)) present in lecithin may also be preferably used. These lecithins or lecithin derivatives may be used alone or in combination of two or more. Lecithin used in the present invention can be commercially obtained from, for example, SLP-PC35 (phosphatidylcholine (hereinafter sometimes abbreviated as PC) content: 35%), SLP-PC70(PC content: 70%), SLP-White Lyso (lysolecithin) (manufactured by Tsuji oil (stock Co., Ltd.)); yolk lecithin LPL-20S, LPL-20W (lysophospholipid content about 20%), yolk lecithin PL-30S (phosphatidylcholine content about 30%) (or more, manufactured by Kjeldahl (Kewpie) (thigh.)); soybean lecithin, egg yolk lecithin, phosphatidylcholine, phosphatidylserine, glycerophosphocholine (see above, manufactured by h.holstein corporation); leheptagolin (Lecigran) (powdered lecithin), Metarin (fractionated lecithin), and leheptamustine (lecithin) (powdered lysolecithin) (manufactured by Cargill corporation, supra); lesaonn p (Lecion p) (phospholipid content 90% or more), Lecion LP-1 (lecithin content about 70%), lecithle (Lecimale) (enzymatically decomposed lecithin, phospholipid content 50%) (or more, manufactured by Riken Vitamin corporation); force to excellent PS25(Nichiyu PS25) (phosphatidylserine content about 25%), Nichiyu PS50 (phosphatidylserine content about 50%); mulberry lecithin A-1(San lecithin A-1) (soybean lecithin enzymatically decomposed, lecithin content about 30%), and the like.
The anti-skin aging external composition of the present invention is effective for skin aging, particularly wrinkles or sagging of skin, and can be preferably used for inhibiting wrinkles or sagging of skin. Further, it may be used for suppressing skin aging caused by aging, but it is preferably used for suppressing skin aging caused by light. Can be preferably used for suppressing skin aging caused by irradiation of ultraviolet rays (particularly UVA) in light.
In addition, the external composition for anti-skin aging of the present invention can be preferably used as a composition for inhibiting the production of Reactive Oxygen Species (ROS) and/or a composition for inhibiting the production of Matrix Metalloproteinases (MMPs). Can effectively inhibit MMP-1, MMP-2 and MMP-9 in MMP.
When the anti-skin aging external composition of the present invention is an external composition containing a liposome containing gamma-oryzanol, the composition can exert an MMP production inhibitory effect particularly well against MMP-2 and MMP-9. In addition, when the anti-skin aging external composition of the present invention is an external composition containing liposome non-entrapped γ -oryzanol, the MMP production inhibitory effect can be particularly well exerted on MMP-1.
For example, other components may be added to gamma-oryzanol for use as the anti-skin aging external composition of the present invention. For example, the liposome suspension may be used as it is or other components may be added to the liposome suspension as the external composition for anti-skin aging of the present invention.
Examples of the other components include a polymer, a protein or a hydrolysate thereof, mucopolysaccharides (mucopolysaccharides), and the like. Examples of the polymer include, but are not limited to, carboxyvinyl polymers, xanthan gum, sodium alginate, and the like. Preferred are carboxyvinyl polymers and xanthan gum, and particularly preferred are carboxyvinyl polymers. These polymers may be used alone or in combination of two or more. The amount of the polymer to be blended is not particularly limited, but is 0.001% to 20%, preferably 0.005% to 10%, and particularly preferably 0.01% to 5%. Examples of the protein and its hydrolysate include collagen, elastin, keratin, casein, hydrolysates thereof, salts of hydrolysates, esters of hydrolysates, or enzymatically treated hydrolysates, with collagen being particularly preferred. The amount of the protein or hydrolysate thereof to be blended is not particularly limited, but is 0.001% to 5%, preferably 0.01% to 1%. Examples of mucopolysaccharides include chondroitin sulfate (chondroitin sulfate), hyaluronic acid, dermatan sulfate (dermatan sulfate), heparan sulfate (heparan sulfate), mucoitin sulfate (mucoitin sulfate), heparin, derivatives thereof, and salts thereof, and chondroitin sulfate, hyaluronic acid, and sodium salts thereof are particularly preferable. The amount of the mucopolysaccharide to be blended is not particularly limited, but is 0.0005% to 5%, preferably 0.001% to 1%.
In addition, well-known components (contained in the continuous phase of the liposome dispersion liquid) generally used in external compositions may be blended within a range not impairing the effects of the present invention. Examples of such components include: humectant, water-soluble polymer, oil component, colorant, antioxidant, metal chelating agent, antiseptic, pH regulator, algefacient, perfume, ultraviolet absorbing/scattering agent, antioxidant, and medicinal component.
In addition, when the anti-skin aging external composition of the present invention contains a liposome containing γ -oryzanol therein, the components that can be usually contained in the liposome may be used in the process of preparing the liposome within a range that does not impair the effect of the present invention. For example, the following may be exemplified: antioxidants such as ascorbic acid, organic acids such as lactic acid and citric acid, lipids such as phosphatidylglycerol and phosphatidylethanolamine, natural polymers such as chitosan (chitosan), fucoidan (fucoidan) and hyaluronic acid, synthetic polymers such as polyethylene glycol and carboxyvinyl polymers, saccharides such as trehalose (trehalose), lactulose (lactulose) and maltitol (maltotol), and polyols such as glycerol.
The composition for external use of the present invention is preferably used as a composition particularly suitable for the skin. Examples of the composition for external use include pharmaceutical compositions, quasi drug (quasisdrug) compositions, and cosmetic compositions. The dosage form is not particularly limited, but examples thereof include a mask, a cream, an ointment, a cream, a gel, a skin lotion, an emulsion, a beauty lotion, a cosmetic water, and a spray.
The subject to which the external composition for anti-skin aging of the present invention is applied is not particularly limited, but is preferably a person who desires anti-skin aging (particularly inhibition of wrinkles or sagging).
As described above, the anti-skin-aging external composition of the present invention exerts an anti-skin aging effect by achieving an effect of inhibiting (particularly, reducing) Reactive Oxygen Species (ROS) and/or an effect of inhibiting Matrix Metalloproteinases (MMPs) through the enhancement of antioxidant gene expression. Thus, the present invention also includes: an external composition for enhancing expression of an antioxidant gene comprising gamma-oryzanol (preferably liposome containing gamma-oryzanol), and an external composition for inhibiting MMP comprising gamma-oryzanol (preferably liposome containing gamma-oryzanol).
Examples of the antioxidant gene include: nrf2(NFE2related factor 2), Nqo1(NAD (P) Hquinone oxide detect tase1), HO-1(heme oxide synthase-1), and SOD1(Superoxide dismutase 1). At least one antioxidant gene selected from the group consisting of Nrf2, Nqo1, HO-1 and SOD1 is preferable, and Nrf2 gene and/or Nqo1 gene is particularly preferable.
Further, as the MMP to be inhibited, MMP-1, MMP-2, and MMP-9 are particularly preferable.
Nrf2 is a transcription factor that is activated by active oxygen and the like to control oxidative stress adaptation in higher animals in a unified manner. Nrf2 enhances gene expression of a foreign-substance metabolizing enzyme such as Glutathione S-transferase (GST) or Nqo1, Glutathione synthetase, and the like, which are detoxifying enzymes for electrophilic substances, and detoxifies the electrophilic substances. Heme oxygenase 1(HO-1) is known to be derived from various acute stresses, including oxidative stress, and is also one of the Nrf 2-targeted genes. Superoxide dismutase (SOD) is an enzyme that decomposes active oxygen that has been produced inside cells, and three SODs are present in mammals, and SOD1 is present in cytoplasm.
In addition, in The present specification, The term "comprising" includes "consisting essentially of … …" and "consisting of … …" (The term "comprising" includes "and" connecting of. ").
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