WO2012043780A1

WO2012043780A1 - Orally ingestible skin activator and process for production thereof

Info

Publication number: WO2012043780A1
Application number: PCT/JP2011/072507
Authority: WO
Inventors: 直樹高石; 西川　善弘; 木村　隆
Original assignee: ユニチカ株式会社
Priority date: 2010-09-30
Filing date: 2011-09-30
Publication date: 2012-04-05
Also published as: JP5847723B2; JPWO2012043780A1

Abstract

Provided is an orally ingestible skin activator characterized by containing an acidic phospholipid at a content of 40 mass% or more. The acidic phospholipid is preferably a phosphatidic acid and/or lysophosphatidic acid.

Description

Skin activator for ingestion and method for producing the same

The present invention relates to a skin activator for oral intake and a method for producing the skin activator for oral intake.

Phospholipids are known as major components for constituting biological membranes, as are proteins. More specifically, phospholipids form lipid bilayers in cell membranes or form lysosomes that are used for mass transfer inside and outside the cell membrane, and are specifically present in the cell membrane, such as the brain, nerves, It is abundant in parts such as internal organs, blood, eggs, and seeds. Phospholipids fulfill many functions for life support. In recent years, various studies have been made to clarify the functionality of various phospholipids.

For example, JP2004-59496A and JP2005-272444A describe phosphatidylcholine which is a main component for constituting lecithin which is a kind of phospholipid. Furthermore, it is described that this phosphatidylcholine has a whitening effect on the skin. Furthermore, J. et al. Lab. Clin. Med. 139 (2002), pages 202-210, describes that phosphatidylcholine suppresses excessive collagen production resulting from inflammatory stimuli in the skin.

J. Invest. Surg. 17 (2004), pp. 15-22, it is described that phosphatidylcholine has an action of suppressing the contraction expressed in damaged skin and recovering damaged skin more effectively. ing. JP 2006-76967 A describes that phosphatidic acid, which is a kind of phospholipid, has an action of activating protein kinase C and promoting hair regeneration.

JP 2006-143744A describes that phosphatidic acid is effective in the treatment of cancer, particularly in the treatment of cancer that has acquired multidrug resistance. More specifically, it is described that phosphatidic acid improves cancer symptoms by increasing the fluidity of the cell membrane of tumor cells and inhibiting multidrug resistance to various cytotoxic drugs. .

Furthermore, Protein material, Nucleic acid, Enzyme, Vol. 44, no. 8 (1999), pages 1118 to 1125, show that lysophosphatidic acid, which is a kind of phospholipid, has an action of proliferating cells, and cyclic lysophosphatidic acid, which is a kind of phospholipid, It has been reported to have an effect of inhibiting proliferation.

As an example of examining the functionality of phospholipids, in addition to the above, FOOD Style 21, Vol. 6, no. 11 (2002), pages 108 to 116, it is described that phosphatidylserine, a kind of phospholipid, has an effect of improving brain function. Japan Agricultural Chemistry 2004 Annual Meeting, 3A19, page 23, “Effects on neurite elongation of phosphatidylserine bioreductive biofouling” , And Agrochemistry 2004, 3A19, page 23), it is described that phosphatidylserine has an activity of extending neurites.

J. Lipid Research, 47 (2006), pages 1434 to 1443 describes that phosphatidylethanolamine, a kind of phospholipid, has a function of imparting nutrition to nerves. Japanese Patent No. 2717509 describes that acidic phospholipids and lyso forms thereof have an action of reducing bitterness. Furthermore, the present inventors have reported in WO2009 / 028220 that collagen production is promoted when glycerophospholipid, a kind of phospholipid, is administered to normal human skin fibroblasts and rats. ing.

However, by ingesting acidic phospholipids, especially lysophosphatidic acid or phosphatidic acid, by activating the metabolism of skin tissue, skin activating effects such as promotion of wound healing and prevention of photoaging are expressed at all. unknown. In addition, the mechanism of these skin activation actions cannot be explained only by the effect of promoting collagen production, and the details are unknown.

For example, the following are known as ingredients and foods that cause skin activation by ingestion. That is, in Japanese Patent No. 3308433, skin activation food comprising Tonaka, ginseng and collagen as essential components, and one or more selected from the group consisting of deoxyribonucleic acid, chondroitin sulfate and pearl extract. Is described. JP2002-255847A describes a food containing a collagen production promoter containing a tripeptide composed of glycine and other amino acids as an active ingredient.

JP2000-95701A describes a skin activator containing a fruit of prunes or an extract thereof. JP 62-6690B describes a skin activator for oral consumption containing an aqueous extract of Ouren detoxification water, Psycho, Kouka and Yokuinin as active ingredients. JP 3-00000024B describes a skin activating food containing, as an active ingredient, an extract obtained by extracting a crude drug mixture composed of seri, sancin, mirabilis, kouca, turmeric and yokuinin from water or aqueous alcohol.

However, since the conventional ingredients having the skin activating action as described above are obtained from plant materials derived from natural products such as herbal medicines, it is difficult to stably control the quality. Furthermore, since the conventional component which has the above skin activating effect | action cannot fully express a skin activating effect when the intake amount is small, it is necessary to increase the intake amount. In addition, when the intake amount of the component having the skin activating action as described above increases, there may be a problem that gastrointestinal upset symptoms such as diarrhea occur.

Also, phosphatidic acid and lysophosphatidic acid are the most basic glycerophospholipids and have been studied for a long time. In addition, phosphatidic acid and lysophosphatidic acid are widely distributed as metabolic intermediates or precursors in lipid extracts obtained from various biological tissues.

FEBES Lett. 531 (2002), pp. 65-68, describes that phosphatidic acid has a function as a lipidic signal factor and interacts with various proteins. Science, 294 (2001), pages 1942 to 1945, describes that a protein called m-TOR (mammalian target of rapamycin) is directly activated by phosphatidic acid. Yes.

However, it is not known at all that phosphatidic acid or lysophosphatidic acid has a skin activating action such as a wound healing promoting action or a photoaging prevention action.

Here, the process of wound healing consists of four stages: blood coagulation phase, inflammation phase, growth phase and maturation phase. Each stage in the wound healing process will be described below. That is, the blood coagulation phase is a stage where the wound is temporarily closed by the coagulated blood. That is, the blood coagulation phase is regarded as a stage where an emergency treatment is applied to an external enemy entering the wound. During the inflammatory phase, neutrophils and macrophages migrate to the wound part, so that attached bacteria, necrotic tissue, or foreign substances are taken up and eliminated. In the proliferative phase, fibroblasts produce extracellular matrix components such as collagen, and new blood vessels are formed, and accordingly granulation tissue is formed and the wound contracts. In the mature period, the production of extracellular matrix components proceeds sufficiently and the wound becomes inconspicuous.

In this wound healing process, various growth factors are involved. Among the growth factors, it has become clear that cells such as macrophages that play a part of the immune system play an important role. That is, wound healing has been shown to be a physiological process through the immune system.

In healthy patients, the above wound healing process will surely proceed. However, in diabetic patients, migration of cells such as macrophages is slow, or the production amount of growth factor is decreased. For this reason, healing of wounds may be delayed or healing may not proceed at all, which causes major clinical problems.

As a treatment method for wounds, from the viewpoint of allowing the wound to heal quickly, a treatment method in which gauze is applied to a wound part that has been disinfected; dressing agents such as polyurethane films, hydrocolloids, hydrogels, and hydropolymers are used. So-called wet therapy is widely applied. However, even when a gauze treatment or wet therapy is used, wound healing is still delayed in diabetic patients, and it cannot be said that wound treatment is sufficient.

Based on this situation, Arzneimtelforschun. 46 (5), (1996), pages 547-551, and Basis and The medical practice, 30 (9), (1996), pages 2161-2174. The basic fibroblast growth factor (bFGF) is described. bFGF has an action of growing fibroblasts and promoting angiogenesis, and can perform sufficient wound healing even in diabetic patients.

BFGF preparation is commercially available under the trade name of Fiblast Spray. And since the outstanding wound healing effect can be exhibited by using the local administration method of spraying the solution of bFGF preparation to an affected part, bFGF preparation is used frequently in the clinical field of surgery. However, when the above-mentioned local administration method is used, since bFGF is a growth factor, there is a concern that it may cause an increase in the tumor in a patient having a tumor near the wound. That is, since the above bFGF cannot be applied to such a patient, there is a problem that bFGF is not necessarily excellent from the viewpoint of versatility.

In addition, Medical Biology, 63 (1985), pages 73-85; Surgery, 104 (1988), pages 224-230; The Journal of vegetarian medical science, 67 (1) (2005). 111) -114; JP11-116604A and JP11-171784A contain active ingredients such as polysaccharides extracted from Meshimakobu, yeast-derived β-glucan, or sulfated β-1,3-glucan. It is described that a wound healing promoting action is expressed by local administration to a wound part. However, when the above-mentioned active ingredient is administered locally, the active ingredient is applied directly to the wound surface or administered systemically by intravenous injection. A component that exhibits an action is desired.

JP2009-143854A describes Hanabiratake as a component that exhibits an effect of promoting wound healing by oral ingestion. However, Hanabiratake is relatively expensive and has a problem in that it needs to increase the amount of intake necessary to exert the effect of promoting wound healing.

By the way, the appearance of aging in the skin is often a problem. In general, skin aging is a combination of natural aging with aging and photoaging due to repeated exposure to ultraviolet rays. Skin that has undergone aging due to natural aging exhibits smooth and fine wrinkles, whereas skin that has undergone photoaging has rough and deep wrinkles. In addition, photoaging occurs when the sun (ultraviolet rays) continues to be applied for a long period of time. It is known that photoaging causes deep wrinkles on the face, neck and the like, and further causes dry skin, rough skin, and pigmentation such as spots and freckles. In recent years, skin troubles caused by photoaging have become particularly problematic.

Cosmetics containing various UV absorbing materials such as titanium oxide, zinc oxide, paramethoxy percutaneous acid ester, paraaminobenzoic acid ester, UV scattering material, UV shielding material, etc. Sunscreen and sun protect cosmetics) are used. As a method for improving symptoms caused by photoaging of the skin, it is widely known that administration of botulinum toxin by skin injection is effective. However, since the skin injection may be inferior in safety such as causing rough skin, it is limited to use only by a doctor, and is not preferable from the viewpoint of versatility. Further, all-trans retinoic acid (tretinoin) and the like are known as external preparations that can be directly applied to the skin to improve symptoms caused by photoaging of the skin.

On the other hand, in recent years, from the concept of ingesting cosmetic ingredients in the body, in addition to directly applying the above-mentioned external preparations directly to the skin, the effect of preventing or improving photoaging by daily ingestion There is a need for food ingredients that exhibit

As a food ingredient exhibiting these actions, JP2008-280217A describes a phenylethanoid glycoside contained in an extract of a plant of the genus Oleaceae. JP2010-506893A describes a composition for oral administration containing glucosamine and one or more polyphenol compounds derived from pine bark. Biosci. Biotechnol. Biochem. 73 (4) (2009), pages 930 to 932 describe collagen peptides as food ingredients that have the effect of preventing or improving photoaging.

However, these food ingredients have a problem that safety cannot be guaranteed because human food experience is small. Moreover, since these food ingredients are less effective when the intake is small, there is a problem that a large intake is necessary.

In addition, J. Lipid Res. 49 (2008), pages 1235-1245, it is reported that phosphatidylserine is effectively administered to the wound site as a preventive or therapeutic treatment for photoaging. By locally administering phosphatidylserine, a decrease in type 1 procollagen in the dermis and an increase in MMP1 (collagenase) caused by UV irradiation are suppressed. However, it is not known at all that photoaging is effectively prevented or improved by ingesting acidic phospholipids, particularly phosphatidic acid or lysophosphatidic acid.

On the other hand, J. Dermatol. 44 (2006), pages 101-107; Health Sci. 54 (2008), pages 559 to 566, it is known that the skin barrier function is improved by ingestion of glycosphingolipid orally. Sphingolipid is a general term for complex lipids containing sphingoids as long-chain base components. That is, a ceramide in which a fatty acid and an acid amide bond to a sphingoid have a common structure and a sugar is glycosidically bonded is called a sphingoglycolipid.

However, the ingestion of a combination of glycosphingolipid and acidic phospholipid in synergistically enhances skin activation such as collagen production promoting action, photoaging prevention action, and wound healing promotion action. Was not known at all.

The object of the present invention is to contain acidic phospholipids (particularly phosphatidic acid and / or lysophosphatidic acid), is inexpensive and highly safe, easy to control quality, and provides a sufficient effect with a small amount of intake. It is to provide a skin enhancer for oral consumption. Furthermore, another object of the present invention is to provide a method for producing a skin activator for oral intake that exhibits the above-described effects.

As a result of intensive studies to solve such problems, the present inventors have found that a skin activator for oral consumption having an acidic phospholipid content of 40% by mass or more is particularly excellent in preventing photoaging. The present inventors have found the fact that it has a skin activating action such as an action and a wound healing promoting action, and reached the present invention. Furthermore, it discovered that the skin activator for oral intake which shows a high effect by performing specific operation could be manufactured, and reached | attained this invention.

That is, the gist of the present invention is as follows.
(1) A skin activator for oral intake, wherein the content of acidic phospholipid is 40% by mass or more.
(2) The skin activator for oral consumption according to (1), wherein the acidic phospholipid is phosphatidic acid and / or lysophosphatidic acid.
(3) The skin activator for oral intake according to (1) or (2), which can be used in combination with collagens.
(4) The skin activator for oral intake according to any one of (1) to (3), which can be used in combination with glycosphingolipid.
(5) A food or drink containing the skin activator for oral intake according to any one of (1) to (4).
(6) A method for producing an oral ingestion skin activator according to any one of (1) to (4), comprising a step of allowing a phospholipase to act on a lipid mixture containing a neutral phospholipid; The manufacturing method of the skin activator for oral consumption characterized by including the process of removing the neutral lipid contained.

According to the present invention, it is possible to provide a skin activator for oral ingestion that is inexpensive, high in safety, easy in quality control, and can obtain a sufficient effect with a small amount of ingestion. Since these skin ingestants for oral intake are made from acidic phospholipids that have been used for food since ancient times, they are extremely safe and can be used in oral administrations such as foods and drinks and supplements. Therefore, when orally administering the skin activator for oral intake, it is possible to appropriately select administration conditions (dosage, number of administrations, etc.) suitable for each subject.

It is a graph showing the photoaging prevention effect (the reduction | decrease prevention effect of the moisture content in a stratum corneum) of the skin activator for oral intake of this invention.

The present invention will be described below.
The skin activator for oral intake of the present invention activates the metabolism of skin tissue, thereby preventing the skin from getting firm and shiny and improving fine wrinkles or dullness. In particular, it has the effect of effectively preventing photoaging due to repeated exposure to ultraviolet rays. Furthermore, the skin activator for oral intake of the present invention has effects other than the collagen production promoting effect and the cosmetic effect, that is, the effect of promoting wound healing.

In this specification, the wound refers to physical damage to the body surface tissue caused by external and internal factors. Specific examples include cuts, lacerations, puncture wounds, bite wounds, abrasions, gunshot wounds, contusions, burns, or pressure sores.

The skin activator for oral intake of the present invention is taken into the body by oral administration. When administered orally, it does not go through the stratum corneum of the skin, so it is more likely to reach the dermis layer of the skin as compared to the case where it is ingested after being applied in the form of an ointment or lotion. As a result, even with a small amount of ingestion, the skin activation effect is remarkably excellent. In addition, in order to ingest the skin activator for oral intake of this invention in a body, it should just be contained and used for a pharmaceutical, food-drinks, etc.

The skin activator for oral intake of the present invention contains acidic phospholipid. The acidic phospholipid as used herein refers to a phospholipid having a negative charge as a whole molecule in physiological saline, among glycerophospholipids having a central skeleton composed of glycerin, fatty acid and phosphoric acid.

Examples of acidic phospholipids include phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylinositol (PI), or lyso forms in which fatty acids are removed from them. Among these, from the viewpoint of having a high skin activating effect, phosphatidic acid or lysophosphatidic acid in which the C1- or C2-position fatty acid is removed from phosphatidic acid is preferable, and phosphatidic acid is particularly preferable.

In the skin activator for oral intake of the present invention, the content of acidic phospholipid is required to be 40% by mass or more. The present invention, by orally ingesting a skin activating agent containing acidic phospholipids at a high rate, exhibits a significant skin activating effect compared to the prior art, and has a wound healing promoting effect and a photoaging prevention effect. It has been found for the first time that it is played more effectively. From the viewpoint of more effectively expressing these effects, the content of the acidic phospholipid of the skin activator for oral intake of the present invention is preferably 60% by mass or more, more preferably 70% by mass or more. . The reason why the content of the acidic phospholipid is required to be 40% by mass or more is not clear, but is presumed to be as follows. That is, since the skin activator of the present invention is for oral intake, the amount of acidic phospholipid may be reduced due to decomposition in the stomach and intestine at the time of intake. However, even in such a case, when the content is 40% by mass or more, it is presumed that the skin activation effect can be expressed without being affected by the decrease in acidic phospholipid.

The neutral phospholipid may be contained in the skin activator for oral intake of the present invention. Neutral phospholipid refers to a phospholipid having a central skeleton composed of glycerin, a fatty acid, and phosphoric acid that does not show a charge as a whole molecule in physiological saline. Specific examples of neutral phospholipids include phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their lysates.

Acidic phospholipids and neutral phospholipids have a basic skeleton composed of glycerin, fatty acids and phosphoric acid as described above. The fatty acid is preferably, for example, a saturated fatty acid having 8 to 24 carbon atoms, or an unsaturated fatty acid having an unsaturation degree of 1 or more and 4 to 30 carbon atoms.

The fatty acid is not particularly limited, and specific examples thereof include the following linear unsaturated fatty acids. Butenoic acid such as crotonic acid and isocrotonic acid (carbon number: 4, unsaturation degree: 1); pentenoic acid (carbon number: 5, unsaturation degree: 1); hexenoic acid (carbon number: 6, unsaturation degree: 1) ); Heptenoic acid (carbon number: 7, unsaturated degree: 1); octenoic acid (carbon number: 8, unsaturated degree: 1); nonenoic acid (carbon number: 9, unsaturated degree: 1); decenoic acid ( Carbon number: 10, unsaturation degree: 1); undecenoic acid (carbon number: 11, unsaturation degree: 1); dodecenoic acid such as lauroleic acid (carbon number: 12, unsaturation degree: 1); tridecenoic acid (carbon) Number: 13, Unsaturation: 1); Tetradecenoic acid (carbon number: 14, unsaturation degree: 1) such as myristoleic acid and mysteridine acid; pentadecenoic acid (carbon number: 15, unsaturation degree: 1) Hexadecenoic acid such as palmitoleic acid and palmiteraidic acid (carbon number: 16, Consistency: 1); heptadecenoic acid (carbon number: 17, unsaturation degree: 1); octadecenoic acid (carbon number: 18, unsaturation degree) such as petroceric acid, petroceridic acid, oleic acid, elaidic acid, vaccenic acid 1); nonadecenoic acid (carbon number: 19, unsaturation degree: 1); eicosenoic acid such as gadoleic acid and gondrenic acid (carbon number: 20, unsaturation degree: 1); erucic acid, brassicic acid, setoleic acid, etc. Of docosenoic acid (carbon number: 22, unsaturation degree: 1); tetracosenoic acid such as nervonic acid (carbon number: 24, unsaturation degree: 1); hexacosenoic acid (carbon number: 26, unsaturation degree: 1); Octacosenoic acid (carbon number: 28, unsaturation degree: 1); triacontenoic acid (carbon number: 30, unsaturation degree: 1); pentadienoic acid (carbon number: 5, unsaturation degree: 2); sorbic acid, etc. Hexadienoic acid Carbon number: 6, unsaturation degree: 2); peptadienoic acid (carbon number: 7, unsaturation degree: 2); octadienoic acid (carbon number: 8, unsaturation degree: 2); nonadienoic acid (carbon number: 9, Decadienoic acid (carbon number: 10, unsaturation degree: 2); Undecadienoic acid (carbon number: 11, unsaturation degree: 2); Dodecadienoic acid (carbon number: 12, unsaturation degree: 2) ); Tridecadienoic acid (carbon number: 13, unsaturation degree: 2); tetradecadienoic acid (carbon number: 14, unsaturation degree: 2); pentadecadienoic acid (carbon number: 15, unsaturation degree: 2) Hexadecadienoic acid (carbon number: 16, unsaturation degree: 2); hepadecadienoic acid (carbon number: 17, unsaturation degree: 2); octadecadienoic acid such as linoleic acid and linoelaidic acid (carbon number: 18); , Degree of unsaturation: 2); eicosadienoic acid (carbon number: 20, unsaturated) Degree: 2); docosadienoic acid (carbon number: 22, unsaturation degree: 2); tetracosadenoic acid (carbon number: 24, unsaturation degree: 2); hexacosadenoic acid (carbon number: 26, unsaturation degree: 2); Octacosadienoic acid (carbon number: 28, unsaturation degree: 2); triacontadienoic acid (carbon number: 30, unsaturation degree: 2); hexadecatrienoic acid (carbon number: 16, unsaturation degree: 3); α -Octadecatrienoic acid such as linolenic acid and γ-linolenic acid (carbon number: 18, unsaturation level: 3); dihomo-γ-linolenic acid; eicosatrienoic acid such as mede acid (carbon number: 20, unsaturated) Degree: 3); docosatrienoic acid (carbon number: 22, unsaturation degree: 3); tetracosatrienoic acid (carbon number: 24, unsaturation degree: 3); hexacosatrienoic acid (carbon number: 26, degree of unsaturation) : 3); Octacosatrienoic acid (carbon number; 8, Unsaturation degree: 3); Triacontatrienoic acid (carbon number: 30, unsaturation degree: 3); Octadecatetraenoic acid such as stearidonic acid (carbon number: 18, unsaturation degree: 4); Arachidonic acid Eicosatetraenoic acid (carbon number: 20, molecular weight: 4); docosatetraenoic acid (carbon number: 22, unsaturation degree: 4) such as adrenic acid; tetracosatetraenoic acid (carbon number: 24, Unsaturation degree: 4); Hexacosatetraenoic acid (carbon number: 26, unsaturation degree: 4); Octacosatetraenoic acid (carbon number: 28, unsaturation degree: 4); Triacatatetraenoic acid (carbon Number: 30; Unsaturation degree: 4); Eicosapentaenoic acid (carbon number: 20, unsaturation degree: 5); Docosapentaenoic acid such as crupadonic acid (carbon number: 22, unsaturation degree: 5); Tetracosa Pentaenoic acid (24 carbon atoms, unsatisfactory Degree: 5); docosahexaenoic acid (carbon number: 22, degree of unsaturation: 6); tetracosahexaenoic acid such as herring acid (carbon number: 24, degree of unsaturation: 6), and the like. Of these, oleic acid and linoleic acid are preferred from the viewpoint of the skin activation effect.

In addition to the linear unsaturated fatty acids shown above, rumenic acid (carbon number: 18, unsaturation degree: 2), calendic acid (carbon number: 18, unsaturation degree: 3), jacaric acid (carbon number: 18) Unsaturation degree: 3), eleostearic acid (carbon number: 18, unsaturation degree: 3), catalpinic acid (carbon number: 18, unsaturation degree: 3), punicic acid (carbon number: 18, unsaturation) Degrees: 3) Conjugated fatty acids such as luminenic acid (carbon number: 18, unsaturation degree: 3); ricinoleic acid (carbon number: 18, unsaturation degree: 1) and ricinaleic acid (carbon number: 18, unsaturated) Degree: 1), hydroxylated unsaturated fatty acid such as dimorphecolic acid (carbon number: 18, unsaturation degree: 2); epoxy fatty acid such as bemorinic acid (carbon number: 18, unsaturation degree: 1); Furanoid fatty acids such as urofuranic acid; high molecular weight branching such as mycolic acid Unsaturated fatty acids; and other methoxy unsaturated fatty acids and cyclic unsaturated fatty acids. These fatty acids are components that can constitute acidic phospholipids or neutral phospholipids, alone or in combination of two or more.

From the viewpoint of skin activation effect, the content ratio of acidic phospholipid and neutral phospholipid is (acid phospholipid) / (neutral phospholipid) = 2/1 or more in terms of mass ratio based on acidic phospholipid ( That is, the acidic phospholipid is preferably 2 times or more of the neutral phospholipid), more preferably 5/1 or more, and most preferably 50/1 or more.

The skin activator for oral intake of the present invention is preferably used in combination with collagens. When used in combination with collagens, the synergistic effect of acidic phospholipids and collagens further improves the wound healing action and the photoaging prevention action, and provides a superior skin activation effect.

The reason why the synergistic effect of skin activation can be obtained by combining the skin activator for oral intake of the present invention with collagens is not clear, but is presumed to be as follows. That is, by supplying amino acid derived from acidic phospholipids and collagens to fibroblasts in the skin, fibroblasts are activated by acidic phospholipids. And it is estimated that this activated fibroblast regenerates the skin using amino acids derived from collagen as a raw material.

Examples of collagens are as follows. That is, collagen extracted from connective tissues such as skin, scales, bones and tendons of animals such as cows, pigs, chickens and fish; gelatin obtained by heat extraction of collagen; peptide bonds of telopeptide parts in the collagen structure Soluble collagen obtained by solubilization by enzyme or alkali hydrolysis; collagen hydrolyzate obtained by hydrolyzing collagen or gelatin.

Among collagens, soluble collagen and collagen hydrolyzate are preferred from the viewpoint of excellent absorbability into the body. Among these, a peptide having a molecular weight of 400 or less represented by Gly-XY is particularly preferable from the viewpoint of particularly excellent absorbability into the body. Here, Gly represents glycine. X and Y represent amino acid residues other than glycine, such as proline and 4-hydroxyproline.

Examples of the method for hydrolyzing collagens include a method using a collagenase enzyme, a method using an acid or an alkali, and the like. As the collagenase enzyme, enzymes derived from bacteria such as Clostridium histoticum, Streptomyces parvulus, Streptomyces septatus, actinomycetes or fungi can be used. Moreover, you may use the other protein hydrolase which has a collagen decomposition | disassembly.

When the skin activator for oral intake of the present invention and collagens are used in combination, the combination ratio of both is based on acidic phospholipids. That is, the combined ratio of acidic phospholipids and collagens is preferably (acid phospholipids) / (collagens) = 2/1 to 1/1000 in a mass ratio, and is in the range of 1/1 to 1/500. It is particularly preferred that When the usage-amount of acidic phospholipid exceeds 2 times the usage-amount of collagen, the raw material cost for obtaining the skin activator for oral intake of this invention may become high. On the other hand, when the amount of collagen used exceeds 1000 times the amount of acidic phospholipid used, the skin activation effect by acidic phospholipid may be poor.

In addition, it is a preferable aspect that the skin activator for oral intake of the present invention is used in combination with a glycosphingolipid. When used in combination with glycosphingolipids, the synergistic effect of acidic phospholipids and glycosphingolipids further enhances the wound healing action, the photoaging prevention action, etc., and provides a superior skin activation effect. The reason for the synergistic effect of acidic phospholipid and glycosphingolipid is not clear, but it is presumed that the structure of the glycosphingolipid ceramide skeleton and acidic phospholipid is similar. In particular, when the oral ingestion skin activator of the present invention, collagens and glycosphingolipids are used in combination, the highest skin activation effect is obtained.

Glycosphingolipid is obtained by extraction from a raw material derived from animal tissue or a raw material derived from plant tissue using an organic solvent. Examples of the raw material derived from animal tissue include animal brain tissue such as cow brain; animal skin tissue such as pig epidermis; milk such as milk. Examples of raw materials derived from plant tissues include raw materials derived from cereals such as rice bran, wheat germ, flour and corn; raw materials derived from beans such as soybeans; raw materials derived from root vegetables such as beets; Examples include raw materials derived from rice cakes such as flour; oil cakes such as cottonseed oil cake and rapeseed oil cake. Among these, the thing derived from a plant tissue is preferable at the point of safety | security and the ease of procurement of a raw material, and also from the point that content of sphingoglycolipid is high, a kite powder is more preferable.

The organic solvent used as the extraction solvent when obtaining the glycosphingolipid is not particularly limited as long as it reacts with the glycosphingolipid during extraction and does not impair the effect of the glycosphingolipid. Examples of such organic solvents include alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, and tert-butanol, hexane, pentane, diethyl ether, chloroform, dichloromethane, and acetone. , Acetonitrile, ethyl acetate and the like. Of these, methanol, ethanol, hexane, and acetone are preferable, and ethanol is particularly preferable. One of these organic solvents may be used alone, or a plurality of solvents may be mixed and used. Moreover, when extracting with these organic solvents, in order to raise extraction efficiency, you may add additives, such as surfactant, water, etc. in the range which does not impair the effect of extraction, for example.

When the skin activator for oral intake of the present invention and glycosphingolipid are used in combination, the combination ratio of both is based on acidic phospholipid. That is, the combined ratio of acidic phospholipid and glycosphingolipid is preferably (acid phospholipid) / (sphingoglycolipid) = 1/1 to 1000/1, and 100/1 to 10/1 in mass ratio. It is particularly preferable that the range is If the amount of acidic phospholipid used exceeds 1000 times the amount of glycosphingolipid used, the synergistic effect of the glycosphingolipid may not be obtained. On the other hand, when the amount of glycosphingolipid used exceeds the amount of acidic phospholipid used, the raw material cost of the ingestible skin activator of the present invention may be remarkably increased.

Next, the manufacturing method of the skin activator for oral intake of this invention is demonstrated.
The method for producing a skin activator for oral consumption according to the present invention comprises a step of causing a phospholipase to act on a lipid mixture containing neutral phospholipid (hereinafter sometimes referred to as “enzyme action step”), It includes a step of removing the neutral lipid contained (hereinafter sometimes referred to as “neutral lipid removal step”).

In the enzyme action step, by causing phospholipase to act on the lipid mixture as a raw material, neutral phospholipids contained in the lipid mixture can be converted into acidic phospholipids, and the content of acidic phospholipids can be increased. And in a neutral lipid removal process, content of acidic phospholipid can be raised by removing the neutral lipid contained in this lipid mixture.

That is, in the method for producing a skin activator for oral intake of the present invention, a lipid mixture containing neutral phospholipid is used as a raw material. Then, phospholipase is allowed to act on neutral phospholipids in the lipid mixture, the neutral phospholipids are converted into acidic phospholipids, and the neutral lipids contained in the lipid mixture are removed, thereby removing acidic lipids. A skin activator for ingestion containing phospholipids at a high concentration (that is, 40% by mass or more) can be produced. In addition, in the lipid mixture which is a raw material, the above-mentioned acidic phospholipid may be contained.

Acidic phospholipids are contained in natural products such as soybean, egg yolk and rapeseed. However, in such a natural product, the content of acidic phospholipid is small. Therefore, when extracting acidic phospholipids from a lipid mixture that is a natural product, an operation for increasing the extraction amount is separately required, and the operation becomes complicated, so that it is not a practical extraction method. Therefore, in the present invention, the content of the acidic phospholipid is obtained by using a lipid mixture containing a neutral phospholipid as a raw material, and including a step of converting the neutral phospholipid into an acidic phospholipid by allowing the phospholipase to act on the lipid mixture. Can be easily increased.

In addition to acidic phospholipids and neutral phospholipids, the lipid mixture as a raw material may contain neutral lipids such as glycerin esters of fatty acids. Examples of the glycerin ester of fatty acid include monoglyceride, diglyceride, and triglyceride. The neutral lipid referred to here does not include phospholipids.

The lipid mixture used as a raw material may be a natural product or a synthetic product. Examples of the natural product of the lipid mixture include lecithin. Lecithin usually contains acidic phospholipids, neutral phospholipids, neutral lipids, and glycolipids as main components. Specific examples of lecithin include soybean lecithin, rapeseed lecithin, egg yolk lecithin and the like. Lecithin is used in various fields such as food and medicine. For industrial use, soybean-derived lecithin is preferable from the viewpoint of being able to provide it at low cost.

Examples of lecithin that can be used industrially are listed below. For example, when lecithin is used as a surfactant, a so-called crude lecithin (soy lecithin) separated from soybean crude oil is used. Crude lecithin is generally based on soybean oil containing neutral lipids such as 70 to 65% phospholipids mainly composed of neutral phospholipids, triglycerides, diglycerides and monoglycerides (ie, such soybean oils). And a lipid mixture containing one or more of fatty acids, carbohydrates, proteins, minerals, sterols and pigments as other components.

Also, examples of lecithin that can be used industrially include defatted lecithin obtained by removing neutral lipid and the like from this crude lecithin using a solvent such as acetone. The defatted lecithin is a high-purity lecithin containing a phospholipid containing a neutral phospholipid as a main component in a proportion of 90% by mass or more, and is used as it is in the fields of health foods, pharmaceuticals and the like.

In addition, examples of the composite of the lipid mixture include a reaction product of a di- or mono-glycerin fatty acid ester and a phosphorylating agent. Examples of the phosphorylating agent include diphosphorus pentoxide and phosphorus oxychloride.

The content of the neutral phospholipid in the lipid mixture as the raw material is not particularly limited, but it is 20 to 100% by mass from the viewpoint of obtaining a skin activator for oral consumption containing acidic phospholipid at a high concentration. It is preferably 40 to 100% by mass, more preferably 60 to 100% by mass. In the lipid mixture as a raw material, the content of acidic phospholipid and the content of neutral lipid are not particularly limited.

The enzyme action process will be described. As described above, the enzyme action step is a skin activator for oral intake in which a phospholipase is allowed to act on a lipid mixture as a raw material to convert neutral phospholipid to acidic phospholipid, thereby increasing the content of acidic phospholipid. It is the process of obtaining. By passing through this enzyme action process, an acidic phospholipid can be contained in a high ratio, and a skin activator for oral intake with a significantly enhanced skin activation effect can be produced.

The phospholipase used in the enzyme action step is an enzyme that acts on neutral phospholipids contained in the lipid mixture and can convert neutral phospholipids into acidic phospholipids. Although it does not specifically limit as phospholipase, From a viewpoint of the safety | security to a biological body, microorganisms-derived phospholipase and plant-derived phospholipase are used preferably.

Specific examples of phospholipase include phospholipase D, phospholipase A1, phospholipase A2, and the like. These may be used alone or in combination. In the enzyme action step of the present invention, phospholipase D is preferably used from the viewpoint of the efficiency of converting neutral phospholipids to acidic phospholipids.

Furthermore, in the case of obtaining lysophosphatidic acid as the acidic phospholipid, it is preferable to cause phospholipase A1 or phospholipase A2 to act in addition to phospholipase D. In addition, when phospholipase D, phospholipase A1 and phospholipase A2 are allowed to act simultaneously, phospholipid is converted into phosphatidylglycerol, and the content of acidic phospholipid in the obtained skin ingestion agent for oral consumption may be reduced. This is not preferable.

Phospholipase D is a phospholipid hydrolase. Then, phosphatidylcholine, phosphatidylethanolamine, and the like, which are main components of the cell membrane, are hydrolyzed to produce phosphatidic acid, choline, ethanolamine, and the like. Phospholipase D is widely distributed in living organisms such as plants, algae, mammals, slime molds, and bacteria, and any of them may be used. Moreover, the reaction conditions for phospholipase D are not particularly limited, and can be appropriately selected.

The amount of phospholipase used in the enzyme action step is not particularly limited, but is preferably 0.01 to 1000 units, more preferably 0.05 to 500 units, and more preferably 1 to 200 units per gram of neutral phospholipid. A unit is particularly preferred. If the amount used is less than 0.01 unit, the conversion rate to acidic phospholipid may be very slow. On the other hand, if the amount used exceeds 1000 units, the manufacturing cost may increase. In addition, the unit which is a unit of said usage-amount represents the quantity of the phospholipase which can hydrolyze 1 micromol phosphatidylcholine in 1 minute.

The reaction temperature in the enzyme action step is not particularly limited as long as the phospholipase is not inactivated, but is preferably 5 to 90 ° C., more preferably 20 to 60 ° C. from the viewpoint of production cost and reaction efficiency. The reaction time in the enzyme action step can be appropriately selected depending on the amount of phospholipase used, but various conditions can be set so that the reaction can be completed in 2 to 72 hours from the viewpoint of production cost. preferable.

In the present invention, solvent fractionation may be performed before and / or after the enzyme action step. By performing solvent fractionation, neutral lipids can be removed and acidic phospholipids can be concentrated, and the concentration of acidic phospholipids can be further increased. Examples of the solvent that can be used for solvent fractionation include alcohol, hydrous alcohol, acetone, nonpolar organic solvent, or a mixture thereof.

The alcohol is preferably a lower alcohol having 1 to 4 carbon atoms from the viewpoint of satisfactorily dissolving neutral lipids and the like. Of these, ethanol is preferable from the viewpoint of safety. The hydrous alcohol is preferably a lower alcohol containing 30% by mass or less of water and more preferably a lower alcohol containing 5 to 25% by mass of water from the viewpoint of solubility of neutral lipids and the like.

The nonpolar organic solvent is not particularly limited as long as it can dissolve neutral lipids and the like, but is preferably a liquid hydrocarbon having 4 to 16 carbon atoms from the viewpoint of safety to the human body. Specific examples of the nonpolar organic solvent include alkanes such as butane, pentane, hexane, heptane, octane, decane, dodecane, tetradecane, and hexadecane. These nonpolar organic solvents may be used individually by 1 type, and may mix and use 2 or more types.

In the above solvent fractionation, the amount of the solvent used varies depending on the components constituting the starting lipid mixture, but is preferably 0.2 to 100 times the mass of the lipid mixture from the viewpoint of ease of handling. More preferably, it is 0.5 to 30 times by mass, particularly preferably 1 to 10 times by mass.

When performing the solvent fractionation described above, when an acidic phospholipid is contained in the starting lipid mixture, an operation of concentrating the acidic phospholipid is preferably included. As the concentration operation, there is a method of extracting and concentrating neutral phospholipids using the solvent by utilizing the fact that neutral phospholipids such as PC and PE in the lipid mixture are easily dissolved in the solvent.

The method for solvent fractionation is described below. For example, when using a lipid mixture containing PC and / or PE as neutral phospholipids and PI and / or PA as acidic phospholipids, such as soybean lecithin, extraction with a solvent is performed. First, the content of PC in the lipid mixture is decreased, and then the content of PE is decreased. By repeating such an extraction operation, it is possible to finally concentrate PI and PA, which are acidic phospholipids, and to produce a skin activator for oral intake having a higher content thereof.

The above solvent fractionation can be performed in a liquid-liquid system. For example, acidic phospholipids can be concentrated to the nonpolar organic solvent side by repeating extraction in a liquid-liquid system using a nonpolar organic solvent and a hydrous lower alcohol.

An example of solvent fractionation operation is given below. That is, the lipid mixture is dissolved in a nonpolar organic solvent in an amount of 0.1 to 100 times, preferably 0.5 to 50 times, the amount of acidic phospholipid. Next, 5 to 25% by mass of a hydrous lower alcohol solution is used in an amount of 0.1 to 10 times by mass, preferably 0.5 to 2.0% by mass, with respect to the obtained solution containing a nonpolar organic solvent. By extracting at twice the amount used, the acidic phospholipid can be concentrated to the nonpolar solvent side.

Next, the neutral lipid removal step will be described. A neutral lipid removal process is a process of removing the neutral lipid contained in the lipid mixture which is a raw material. By passing through the neutral lipid removal step, the concentration of acidic phospholipid in the obtained skin ingestion agent for oral intake can be further increased, and as a result, the skin activation effect can be more remarkably improved.

The neutral lipid may be removed after the enzyme action step. Alternatively, it may be carried out before the enzyme action step, that is, the neutral lipid is previously removed from the raw lipid mixture, and then the lipid mixture from which the neutral lipid is removed may be subjected to the enzyme action step. Or you may implement a neutral lipid removal process in both the front | former stage and back | latter stage of an enzyme action process. Among these, from the viewpoint of increasing the content of acidic phospholipid, it is preferable to carry out the neutral lipid removal step after the enzyme action step.

Specific means for removing neutral lipids include acetone treatment or membrane separation. In particular, acetone treatment is preferable from the viewpoint of simple removal operation.

The acetone treatment will be described below. By performing the acetone treatment, triglyceride, diglyceride, and monoglyceride components that are neutral lipids, or fatty acids, steroids, carotenoids, and the like that are contained therein are dissolved in acetone. On the other hand, acidic phospholipids, neutral phospholipids, and the like, which are insoluble in acetone, are precipitated in acetone. Next, a precipitate containing acid phospholipids and neutral phospholipids is removed by filtration, whereby a lipid mixture having a reduced content of neutral lipids can be obtained. By repeating the above operation, the content of neutral lipid can be reduced, and a skin activator for oral intake with further increased content of acidic phospholipid can be obtained.

The amount of acetone used in the acetone treatment is not particularly limited, but from the viewpoint of ease of handling, it is preferably 0.1 to 100 times by mass with respect to neutral lipid, and 1 to 50 times by mass. Is more preferable.

In the neutral lipid removal step, when a membrane separation method is employed, various known methods can be used. Especially, it is preferable to utilize an ultrafiltration method from a viewpoint of the ease of operation.

In the production method of the present invention, the neutral lipid content is reduced by the neutral lipid removal step. And in the skin activator for oral intake obtained, it is preferable that content of a neutral lipid is less than 5 mass% from a viewpoint of a skin activation effect.

The skin ingestion agent for oral intake of the present invention employs the above-described method, and by increasing the content of acidic phospholipid to 40% by mass or more, it has an excellent skin activation effect even with a small amount of intake. A skin activator for oral consumption can be obtained.

The skin activator for oral intake of the present invention can be used in the form of a liquid, tablet, granule, powder or capsule dispersed in water or oil.

Furthermore, in addition to acidic phospholipids, neutral phospholipids and neutral lipids, the skin activator for oral intake of the present invention includes dextrin, lactose, corn starch, emulsifiers, preservatives, excipients, increasing amounts as necessary. Additives such as agents, sweetening agents, flavoring agents, and coloring agents, and cosmetic ingredients such as ceramide and hyaluronic acid can be contained. Such additives and cosmetic ingredients are added at any stage and concentration as long as the effects of the present invention are not impaired.

The daily intake of the skin activator for oral intake of the present invention is not particularly limited. For example, the intake of acidic phospholipid is about 0.005 to 10 g in an adult male (60 kg). It is preferable to ingest so that the intake amount of acidic phospholipid is 0.01 to 1 g. In addition, the amount of intake can be appropriately increased or decreased depending on sex, weight, physical condition and the like.

When the skin activator for oral consumption of the present invention is contained in a food or drink, it is preferably contained so that the content of acidic phospholipid is 0.001 to 10% by mass relative to the total amount of the food. More preferably, the content is 0.01 to 5% by mass. If the content of acidic phospholipid is less than 0.001% by mass, the skin activation effect may be poor. On the other hand, when content of acidic phospholipid exceeds 10 mass%, raw material cost may become high with respect to the skin activation effect.

Specific examples of the foods and drinks to which the skin activator for oral intake of the present invention is blended include the following. For example, citrus fruits such as grapefruit, orange and lemon and fruit juices containing them; vegetables such as tomatoes, peppers, celery, cucumbers, carrots, potatoes, asparagus and vegetable juices or vegetable juices containing them; sauces, soy sauce, miso, umami Seasonings such as seasonings and chili; soy foods such as tofu and soy milk; emulsified foods such as cream, dressing, mayonnaise and margarine; processed fishery products such as fish meat, surimi and fish eggs; nuts such as peanuts; natto Fermented products; meat and processed meat products; beverages such as beer, coffee, cocoa, black tea, green tea, fermented tea, semi-fermented tea, soft drinks, and functional beverages; pickles; noodles; soups including powdered soup; cheese Milk and other dairy products; bread and cakes; snacks, chewing gum, chocolate and other confectionery; Ndi like; health foods and the like, including a beauty food and drink and the like.

Hereinafter, the present invention will be described specifically by way of examples. The present invention is not limited to these.

Example 1
Comparison of skin activation effects of various phospholipids Using the model animal that produced the wound, the following healing effects of acidic phospholipids and neutral phospholipids (oleate glycerophospholipids) (both manufactured by Sigma) A comparative study was conducted.

(Acid phospholipid)
1-Oleoyl-sn-glycero-3-phosphate sodium salt (hereinafter sometimes referred to as “O-LPA”)
1,2-Dioleyl-sn-glycero-3-phosphate sodium salt (hereinafter sometimes referred to as “DOPA”)
1,2-Dioleoyl-sn-glycero-3-phosphoserine sodium salt (hereinafter sometimes referred to as “DOPS”)
1,2-Dioleoyl-sn-glycero-3-phosphoinositol sodium salt (hereinafter sometimes referred to as “DOPI”)

(Neutral phospholipid)
1,2-Dioleoyl-sn-glycero-3-phosphocholine (hereinafter sometimes referred to as “DOPC”)
1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (hereinafter sometimes referred to as “DOPE”))

ICR mice (16 weeks old, male) (manufactured by CLEA Japan, Inc.) were used as animals for comparative studies. Each of the above phospholipids was diluted in drinking water to obtain an aqueous solution of phospholipid. From two weeks before wound creation, mice were orally administered so that the phospholipid intake was 10 mg / day / kg-BW. In addition, 10 mice were used for each group.

After 2 weeks, the back was removed under anesthesia using a shaver and a hair removal cream, and a full-thickness skin wound (diameter: 8 mm) was created on the left and right sides of the hair removal part with a skin punch. The wound was covered with Tegaderm (coated protective sheet) (manufactured by 3M). The area of the wound after 3 days, 7 days and 11 days was measured using an image scanner (trade name “Epson GT-8000” manufactured by Seiko Epson Corporation), and the progress of healing was observed. In addition, administration of the aqueous solution of phospholipid to the mice was continued until the end of the test. “Mg / day / kg-BW” is a unit indicating the daily intake per kg body weight of a mouse.

Table 1 shows the evaluation results of various phospholipids, with the evaluation of oral administration of physiological saline to the above mice as a comparative control group. In addition, the numerical value of Table 1 represents the relative value (%) of a wound part area when the 0th day is set to 100%. As is apparent from Table 1, the skin activation effect of various phospholipids was higher in the order of DOPA> O-LPA> DOPS> DOPI> DOPC> DOPE.

(Example 2)
Preparation of Oral Ingestion Skin Activator In a 500 ml four-necked flask equipped with a stirrer, 20 g of soy lecithin (manufactured by Sakai Oil Co., Ltd., trade name “SLP-Paste”) and a mixed solution of heptane and ethyl acetate (heptane: (Ethyl acetate = 1: 1, volume ratio) was dissolved in 200 ml. To this mixed solution, 100 ml of 0.1 M Tris / HCl buffer solution (pH: 8.5) containing 0.2 M calcium chloride was added and further stirred. Next, 1000 units of phospholipase D derived from microorganisms (trade name “Actinomadra” SP origin, manufactured by Meika Sangyo Co., Ltd.) was added, and the reaction mixture was allowed to react for 14 hours while maintaining the temperature of the reaction mixture at 30 ° C. So far, it is an enzyme action process.

After the reaction, the reaction product was allowed to stand to separate the solvent layer, and then the solvent was distilled off from the solvent layer under reduced pressure to obtain a lipid mixture. The obtained lipid mixture (15 g) was transferred to a beaker, 85 ml of cold acetone was added under ice-cooling, and phospholipids as an insoluble component were dispersed while being crushed with a spatula. Precipitated. This precipitate was filtered, and the obtained filter cake was dispersed in 85 ml of cold acetone and allowed to stand to precipitate phospholipids, followed by filtration and acetone treatment. This is a neutral lipid removal step. This acetone treatment was repeated twice to obtain 10 g of a skin activator for oral intake.

Table 2 below shows the composition of the oral ingestion skin activator obtained in Example 2 and the raw material soybean lecithin. In addition, the composition in Table 2 is based on mass%.

In addition, said composition analysis was performed using the two-dimensional thin layer chromatography (The product made by Merck, a silica gel plate, brand name "kieselgel"). Two-dimensional thin-layer chromatography is a method in which thin-layer chromatography is continuously developed twice with different solvents (development angle: 90 degrees). As the developing solvent, as a one-dimensional (first developing) solvent, a mixed solution of chloroform, methanol and an aqueous ammonia solution having a concentration of 28% by mass (chloroform / methanol / ammonia aqueous solution having a concentration of 28% by mass = 65 / 35/5, volume ratio), as a two-dimensional (second development) solvent, a mixed solution of chloroform, methanol, acetic acid and water (chloroform / methanol / acetic acid / water = 10/4/2/2, volume) Ratio). After separation, each component was scraped off, and the scraped component was extracted with a mixed solution of chloroform and methanol (chloroform / methanol = 2/1, volume ratio), and after removing the solvent, weighing was obtained.

In Table 2, abbreviations indicate the following.
PC: Phosphatidylcholine PE: Phosphatidylethanolamine PI: Phosphatidylinositol PA: Phosphatidic acid PS: Phosphatidylserine LPA: Lysophosphatidic acid

(Example 3)
Skin activation effect I (Wound healing promoting effect)
The skin activator for ingestion obtained in Example 2 and the raw material soy lecithin were mixed appropriately, and the PA contents were 20% by mass, 30% by mass, 40% by mass, 50% by mass and 60% by mass, respectively. Five kinds of skin activators for oral intake were obtained.

For the ICR mice in which skin full-thickness wounds were created in the same manner as in Example 1, the above five types of skin activators for oral consumption were orally administered so that the PA amount was 10 mg / day / kg-BW. The course of healing was observed over time. The mice were 10 in each group. Table 3 shows the evaluation results of each oral ingestion skin activator, with the evaluation of oral administration of physiological saline to the above mice as a comparative control group. In addition, the numerical value of Table 3 represents the relative value (%) of a wound part area when the 0th day is set to 100%.

From Table 3, it was found that when a skin activator for oral intake having a PA content of 40% by mass or more was used, a higher wound healing effect was exhibited.

Example 4
Skin activating effect of skin activating agent for oral intake II (photoaging prevention effect)
In the five kinds of skin activators for oral consumption whose PA contents prepared in Example 3 are 20% by mass, 30% by mass, 40% by mass, 50% by mass, and 60% by mass, respectively, by the following animal test, Each photoaging effect was evaluated. These phospholipid mixtures were orally administered to 6-week-old hairless mice (Hos / HR-1, male, manufactured by SLC Japan) so that the PA amount was 10 mg / day / kg-BW. The mice were 10 in each group.

Further, it was orally administered and irradiated with UV-B (0.3 mW / cm 2) using a UV-B lamp (manufactured by Sankyo Electric Co., Ltd.). The dose of UV-B was 3 times for 1 minute for the first week, 3 times for 2 minutes for the 2nd week, 3 times for 3 minutes for the 3rd week, 2 times for 4 minutes for the 4th week, In the 5th and 6th weeks, 3 minutes were 7 times. In each group, the stratum corneum moisture content was measured once a week, and the stratum corneum moisture content measured at the fifth week is shown in FIG. The stratum corneum moisture content is measured by placing a mouse in a constant temperature and humidity chamber (20 ± 2 ° C., 50 ± 5%) for 2 hours and then using a Corneometer (trade name “Corneometer CM825” manufactured by Integral). Used. Further, a group in which nothing was ingested and UV-B irradiation was not performed; a group in which nothing was ingested and only UV-B was irradiated was also evaluated.

Note that UVB (−) in FIG. 1 indicates that UV-B irradiation is not performed at all. In addition, the asterisk (*) in FIG. 1 is statistically significantly different from the group (“UVB” group in FIG. 1) irradiated with UVB without taking a skin activator for oral intake. It is shown (p <0.05).

Then, at 6 weeks, the mouse was killed, and the skin of the mouse was excised into a 2 × 2.5 cm rectangle together with the subcutaneous tissue and weighed. After weighing, the extracted skin was added to 10 mL of ice-cooled distilled water, sufficiently homogenized, and the precipitate was collected by centrifugation (7000 rpm × 20 minutes). To this precipitate, 10 mL of ice-cooled 0.1N sodium hydroxide was added, shaken overnight under refrigeration (6 ° C.), the precipitate was collected by centrifugation, and the same operation was performed again.

The precipitate collected by centrifugation was washed with ice-cooled distilled water, and the precipitate was collected again after centrifugation. To this was added 15 mL of ice-cooled 0.5M acetic acid. This was left to stand under refrigeration (6 ° C.) to perform collagen extraction overnight, and then centrifuged to obtain an extracted supernatant. The soluble collagen in the obtained extracted solution was quantified using “Sircol Collagen Assay Kit” (Funakoshi Co., Ltd.). The quantitative results are shown in Table 4.

In FIG. 1 and Table 4, “UVB (−)” indicates that UV-B irradiation is not performed at all, and “UVB” indicates that UV-B irradiation is performed.

As is apparent from FIG. 1 and Table 4, when a skin activator for oral ingestion having a PA content of 40% by mass or more was used, a decrease in the stratum corneum water content by UV-B irradiation, and a further increase in the stratum corneum It has been found that the decrease in the amount of collagen in the lower dermis layer is particularly suppressed.

(Example 5)
Skin activation effect of a skin activator for oral consumption by using a collagen hydrolyzate and / or glycosphingolipid in combination The skin enhancer for oral intake obtained in Example 2 above and the raw material soybean lecithin in mass ratio , (Skin Activator for Oral Ingestion): (Soy Lecithin as a raw material) was formulated to be 42:58 to obtain a skin activating agent for oral intake having a PA content of 40% by mass. Collagen hydrolyzate (“Collagen Tripeptide HACP-01”, manufactured by Zerais Co., Ltd.) and (collagen hydrolyzate): (skin activator for oral ingestion) by mass ratio are added to the skin activator for oral intake. The mixture was formulated to be 9: 1 to obtain Sample A.

In addition, to a skin activator for oral intake having a PA content of 40% by mass obtained as described above, glycosphingolipid derived from konjac powder (manufactured by Unitika Ltd.), the dose to the mouse is A sample B was obtained by blending to give 200 μg / day / kg-BW.

Furthermore, the above-mentioned collagen hydrolyzate in a mass ratio to the above-obtained skin activator having a PA content of 40% by mass, as described above (collagen hydrolyzate): (oral intake) (Skin activating agent) was formulated so as to be 9: 1, and the above glycosphingolipid was further formulated so that the dose to the mouse was 200 μg / day / kg-BW. .

A 6-week-old hairless mouse (Hos / HR-1, male, manufactured by SLC Japan Co., Ltd.) was used in each group, and the above sample A was fed with a skin activator for oral intake of 10 mg / day / kg-BW. The group ingested so that the amount of the skin activator for ingestion was 10 mg / day / kg-BW; the above sample C for ingestion Group ingested so that the amount of skin activator ingested is 10 mg / day / kg-BW; the amount of ingested skin activator in which the content of PA is 40% by mass Group ingested to give 10 mg / day / kg-BW; group ingested only collagen hydrolyzate to ingest 90 mg / day / kg-BW; glycosphingolipid 200 μg / day / kg - W intake and so as ingested were groups of the collagen content after UV-B irradiation in each group were compared according to the method of Example 4. In addition, a group in which nothing was ingested and UV-B irradiation was not performed; a group in which nothing was ingested and only UV-B was ingested was also evaluated.

In each group, the stratum corneum water content at 5 weeks and the collagen content in the skin after 6 weeks were measured in the same manner as in Example 4, and the number of wrinkles on the back of the mice was further evaluated. The number of wrinkles was evaluated by a replica method. That is, a replica was made from the back of a mouse 6 weeks after irradiation with UV-B using a silicone resin (manufactured by Asahi Biomed). Based on the guidelines of the Japan Cosmetic Industry Association, the replica image was analyzed using a reflection replica analysis system ASA-03RXD (manufactured by Asahi Biomed) to determine the number of wrinkles. The number of wrinkles was calculated as the number per μm 2. The results are shown in Table 5.

As is apparent from Table 5, when the skin ingestion agent for oral intake is used in combination with a collagen hydrolyzate or glycosphingolipid, the skin activation effect is higher than when the skin activator for oral intake is used alone. It was a thing. In particular, when a skin activator for oral consumption is used in combination with collagen hydrolyzate and glycosphingolipid, the water content of the stratum corneum is reduced by UV-irradiation, and the dermis layer, which is further below the stratum corneum. The effect of suppressing the decrease in the amount of collagen and the effect of suppressing the generation of wrinkles by UV-irradiation were remarkably excellent.

Note that UVB (-) in Table 5 indicates that no UV-B irradiation was performed. UVB indicates that UV-B irradiation was performed.

The asterisk (*) in Table 5 indicates that there is a statistically significant difference (p <0.05) compared to the UVB group, and the asterisk (**) is statistical compared to the UVB group. There is a significant difference (p <0.01).

The skin activator for oral intake of the present invention is very useful because it is inexpensive, highly safe, easy to quality control, and can provide a sufficient effect with a small amount of intake.

Claims

A skin activator for oral consumption, characterized in that the content of acidic phospholipid is 40% by mass or more.
The skin activator for oral consumption according to claim 1, wherein the acidic phospholipid is phosphatidic acid and / or lysophosphatidic acid.
3. A skin activator for oral consumption according to claim 1 or 2, characterized in that it can be used in combination with collagens.
The skin activator for oral consumption according to any one of claims 1 to 3, which can be used in combination with a glycosphingolipid.
A food or drink comprising the skin activator for oral intake according to any one of claims 1 to 4.
A method for producing a skin activating agent for oral consumption according to any one of claims 1 to 4, comprising a step of allowing a phospholipase to act on a lipid mixture containing a neutral phospholipid, and a medium contained in the lipid mixture. A method for producing a skin activator for ingestion, comprising a step of removing a functional lipid.