WO2015002239A1 - 経口紫外線抵抗性向上剤 - Google Patents
経口紫外線抵抗性向上剤 Download PDFInfo
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- WO2015002239A1 WO2015002239A1 PCT/JP2014/067674 JP2014067674W WO2015002239A1 WO 2015002239 A1 WO2015002239 A1 WO 2015002239A1 JP 2014067674 W JP2014067674 W JP 2014067674W WO 2015002239 A1 WO2015002239 A1 WO 2015002239A1
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- skin
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- lactone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Definitions
- the present invention relates to an oral ultraviolet resistance improver that improves the ultraviolet resistance of skin by oral ingestion.
- UV exposure can cause erythema and edema of the skin, formation of pigmentation, exacerbation of liver and sparrow eggs, decrease of stratum corneum water content, reduced skin barrier function, reduced skin elasticity, Accompanied by the formation of wrinkles, photoelasticity such as photoelasticity and rhomboid skin, and skin tumors.
- Patent Document 1 it has been reported that when Lactobacillus sp is orally ingested, damage to the skin barrier function due to ultraviolet irradiation is suppressed. Further, it has been reported that when a composition containing elastin or ceramide in a carotenoid is orally ingested, erythema of the skin induced by ultraviolet rays can be effectively suppressed (Patent Document 2).
- Glucono- ⁇ -lactone which is a gluconic anhydride, is a sugar lactone in which the hydroxyl group at the 1-position of glucose is replaced with a ketone.
- Glucono- ⁇ -lactone is converted from glucose in vivo by the action of glucose-1-dehydrogenase, and its 6-phosphate derivative is also a metabolic intermediate of the pentose phosphate cycle.
- Glucono- ⁇ -lactone and gluconic acid are both designated as pharmaceuticals and food additives in Japan, and are used as stabilizers, corrigents, pH adjusters, adhesives, acidulants, swelling agents, tofu coagulants, etc. ing.
- Non-Patent Document 1 In recent years, it has been reported that by applying gluconic acid to the skin, IGF-1 secretion is promoted, and effects such as hair growth promotion, skin wrinkling, and sagging reduction are exhibited (Patent Document 3). In addition, it has been reported that by applying glucono- ⁇ -lactone to mouse skin, the skin surface is inclined to the acidic side, the stratum corneum structure is strengthened, and the barrier function is improved (Non-Patent Document 1).
- Patent Document 1 JP 2008-179601
- Patent Document 2 JP 2004-229611
- Patent Document 3 JP 2008-1000094
- the present invention relates to the following 1) to 4).
- An oral ultraviolet resistance improver comprising glucono- ⁇ -lactone as an active ingredient.
- a non-therapeutic method for improving UV resistance in which an effective amount of glucono- ⁇ -lactone is orally administered or ingested.
- a method for improving UV resistance wherein an effective amount of glucono- ⁇ -lactone is orally administered or ingested.
- the figure which shows the ultraviolet-ray-induced erythema and pigmentation inhibitory effect of glucono-delta-lactone The figure which shows the anti-inflammatory (inflammatory cytokine suppression) effect of glucono-delta-lactone.
- the figure which shows the pigmentation inhibitory effect of glucono-delta-lactone The figure which shows the skin barrier function fall inhibitory effect of glucono-delta-lactone. The figure which shows the stratum corneum water content fall inhibitory effect of glucono-delta-lactone. The figure which shows the skin viscoelasticity fall inhibitory effect of glucono-delta-lactone.
- the present invention relates to providing an oral ultraviolet resistance improver that can increase the skin's resistance to ultraviolet rays by ingestion and reduce or suppress skin damage caused by exposure to ultraviolet rays. Furthermore, it is related with providing the non-therapeutic ultraviolet-resistance improvement method which orally administers or ingests the said ultraviolet-resistance improvement agent.
- the present inventors examined an orally ingestible material that improves the ultraviolet resistance of the skin. As a result, it was found that when glucono- ⁇ -lactone was ingested orally, the onset of skin erythema and thickening of the skin due to UV exposure was suppressed. Furthermore, the expression of inflammation-related molecules, melanin synthesis-related molecules, proliferation-related molecules, and dermal degeneration-related factors induced by the ultraviolet rays is suppressed, and glucono- ⁇ -lactone is useful as an oral ultraviolet resistance improver. I found.
- the ultraviolet resistance improver and the like of the present invention are caused by oral ingestion, for example, skin inflammation such as erythema and edema caused by exposure to ultraviolet rays, formation of pigmentation, exacerbation of liver spots and sparrow eggs spots, etc.
- skin inflammation such as erythema and edema caused by exposure to ultraviolet rays, formation of pigmentation, exacerbation of liver spots and sparrow eggs spots, etc.
- skin inflammation such as erythema and edema caused by exposure to ultraviolet rays, formation of pigmentation, exacerbation of liver spots and sparrow eggs spots, etc.
- various skin disorders such as reduced stratum corneum function, reduced skin barrier function, reduced skin elasticity and associated wrinkle formation, sunelasticity, rhomboid skin, skin tumors, and photoaging It is.
- Glucono- ⁇ -lactone used in the ultraviolet resistance improver of the present invention is an intramolecular ester obtained by dehydrating one molecule of water from gluconic acid.
- glucono- ⁇ -lactone When glucono- ⁇ -lactone is dissolved in water, it gradually changes to gluconic acid and reaches an equilibrium state between glucono- ⁇ -lactone and gluconic acid. Accordingly, glucono- ⁇ -lactone is preferred in the present invention, but gluconic acid can also be used.
- non-toxic salts of gluconic acid can be used, such as salts with alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium. And the salt.
- Glucono- ⁇ -lactone or gluconic acid can be produced by a known method, for example, by reacting glucose with molecular oxygen using a palladium catalyst in the presence of an organic solvent (Japanese Patent Laid-Open No. 55-40606).
- gluconic acid solution can be produced by fermenting and oxidizing glucose with certain types of fungi (Penicillium luteum purpurogenum, Penicillium chrysogenum, Aspergillus niger, etc.) or bacteria (Bacterium suboxydans, Bacterium puridum).
- Glucono- ⁇ -lactone can be produced by concentration under reduced pressure (8th edition, Food Additives Official Document (Yodogawa Shoten)).
- glucono- ⁇ -lactone or gluconic acid can be used by purchasing a commercial product that is distributed as a pharmaceutical additive, a food additive, or the like.
- the ingestion of glucono- ⁇ -lactone suppressed the expression of such inflammation-related molecules, melanin synthesis-related molecules, growth-related molecules, and dermal degeneration-related molecules.
- Induced skin inflammation such as erythema and edema of skin, pigmentation, decreased skin barrier function, decreased stratum corneum function, decreased skin barrier function, decreased skin elasticity and accompanying wrinkle formation, skin elasticity This indicates that it is effective in reducing or suppressing skin disorders such as skin aging or skin deterioration such as a decrease in sex.
- glucono- ⁇ -lactone can be used to increase the resistance of skin to ultraviolet rays, that is, it can be used as an ultraviolet resistance improver.
- glucono- ⁇ -lactone can be used to produce the UV resistance improver.
- use of the said ultraviolet-resistance improvement agent may be use (oral administration or ingestion) with respect to a human or a non-human animal, and may be therapeutic use or non-therapeutic use.
- non-therapeutic means a concept that does not include medical practice, that is, a concept that does not include a method for operating, treating, or diagnosing a person, more specifically, a doctor or a person who has received instructions from a doctor It is a concept that does not include a method for performing surgery, treatment, or diagnosis on the subject. Therefore, the composition containing the oral ultraviolet resistance improver of the present invention becomes an oral drug, quasi-drug, supplement or food for improving the resistance of the skin to ultraviolet rays, that is, the oral ultraviolet resistance improver is It is useful as a material or preparation for blending into oral drugs, quasi drugs, supplements or foods.
- the composition containing the oral ultraviolet resistance improver of the present invention is a skin inflammation such as erythema or edema of the skin, pigmentation formation, exacerbation of liver spots, sparrow eggs spots, etc. induced by UV exposure.
- a skin inflammation such as erythema or edema of the skin, pigmentation formation, exacerbation of liver spots, sparrow eggs spots, etc. induced by UV exposure.
- Oral to reduce or inhibit skin damage or photoaging such as reduced stratum corneum function, reduced skin barrier function, reduced skin elasticity and associated wrinkle formation, sunelasticity, rhomboid skin, and skin tumors
- the oral ultraviolet resistance improver is useful as a material or a preparation for blending into an oral drug, a quasi-drug, a supplement, or a food.
- the pharmaceutical, quasi-drug or supplement dosage form may be either a solid preparation or a liquid preparation. Specifically, tablets, coated tablets, capsules, granules, powders, powders, sustained-release preparations, suspensions. Suspensions, emulsions, oral liquids, dragees, pills, fine granules, syrups, elixirs and the like can be mentioned.
- the above preparation can be mixed with a pharmaceutically acceptable carrier.
- suitable carriers include, for example, excipients, binders, disintegrants, lubricants, diluents, osmotic pressure regulators, fluidity promoters, absorption aids, pH adjusters, emulsifiers, preservatives, stabilization.
- a well-known medicinal component can also be suitably mix
- vitamins preferably vitamin B, vitamin C or vitamin E, or a combination thereof (for example, vitamins C and E)
- amino acids preferably vitamin B, vitamin C or vitamin E, or a combination thereof (for example, vitamins C and E)
- amino acids preferably amino acids, peptides and derivatives thereof, nucleic acids and derivatives thereof.
- Saccharides and derivatives thereof, and carotenoids preferably soybean isoflavones, catechins, and antioxidants such as chlorogenic acid.
- the content of glucono- ⁇ -lactone in the preparation is usually 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 0.5% by mass or more, based on the total mass of the formulation, Preferably it is 1 mass% or more and 90 mass% or less, Preferably it is 60 mass% or less.
- 0.01 to 90% by mass preferably 0.1 to 60% by mass, more preferably 0.5 to 60% by mass, and still more preferably 1 to 60% by mass.
- the above foods are caused by ultraviolet rays, skin inflammation such as erythema and edema of the skin, formation of pigmentation, exacerbation of liver spots and sparrow eggs, deterioration of stratum corneum function,
- the concept is to reduce or inhibit skin barrier function, skin elasticity and associated wrinkle formation, skin damage such as photoelasticity and rhomboid skin, or photoaging, and display this as necessary
- Functional foods such as foods for sick persons, functional nutritional foods, health foods or foods for specified health use are included. These functional foods are foods that are distinguished from general foods by labeling.
- Food form may be solid, semi-solid or liquid.
- foods include confectionery such as breads, noodles, cookies, jelly, dairy products, frozen foods, instant foods, processed starch products, processed meat products, other processed foods, carbonated beverages, fruit juice beverages, tea beverages , Beverages such as soft drinks, vegetable drinks, coffee drinks, soups, seasonings, dietary supplements, and the like, and raw materials thereof.
- confectionery such as breads, noodles, cookies, jelly, dairy products, frozen foods, instant foods, processed starch products, processed meat products, other processed foods, carbonated beverages, fruit juice beverages, tea beverages , Beverages such as soft drinks, vegetable drinks, coffee drinks, soups, seasonings, dietary supplements, and the like, and raw materials thereof.
- Beverages such as soft drinks, vegetable drinks, coffee drinks, soups, seasonings, dietary supplements, and the like, and raw materials thereof.
- it may be in tablet form, pill form, capsule form, liquid form, syrup form, powder form, granule form and the like.
- Such foods include any food and drink materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, antioxidants, humectants, thickeners, sticking agents, dispersants, A wetting agent and the like can be mixed and prepared as appropriate.
- various vitamins preferably vitamin B, vitamin C or vitamin E, or a combination thereof (for example, vitamin C and E)
- amino acids and peptides and derivatives thereof amino acids and peptides and derivatives thereof, nucleic acids and derivatives thereof, saccharides and derivatives thereof
- carotenoids, soybean isoflavones, catechins, antioxidant components such as chlorogenic acid, and the like can be appropriately blended.
- the content of glucono- ⁇ -lactone in the food or drink is usually 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 0.2% by mass, although it varies depending on the form of use. % Or more, more preferably 0.4% by mass or more, and 50% by mass or less, preferably 20% by mass or less, and more preferably 10% by mass or less. For example, 0.01 to 50% by mass, preferably 0.1 to 10% by mass, more preferably 0.2 to 10% by mass, and still more preferably 0.4 to 10% by mass.
- the dose or intake may vary according to the human condition, body weight, sex, age or other factors.
- the daily dose per adult is usually 0.01 g or more, preferably 0.05 g or more, more preferably 1 g or more, and more preferably as glucono- ⁇ -lactone. 2 g or more and 10 g or less, preferably 5 g or less.
- the daily dose per adult is, for example, 0.01 to 10 g, preferably 0.05 to 10 g, more preferably 1 to 10 g, and further preferably 2 to 5 g.
- the preparation can be administered according to an arbitrary administration schedule, but it is preferably divided into once to several times a day and continuously administered for several weeks to several months. For example, it is preferable to divide once to 10 times a day and continuously administer or ingest for 1 week or more. More preferably, it is divided into 1 to 5 times a day, and administered or ingested continuously for 2 weeks or more.
- the subject of administration or ingestion is not particularly limited as long as it is an animal that needs or desires it, but skin damage or photoaging induced by UV exposure, such as erythema or edema of the skin.
- Inflammation formation of pigmentation, exacerbation of liver spots and sparrow eggs, decrease of stratum corneum function, decrease of skin barrier function, decrease of skin elasticity and concomitant wrinkles, photoelasticity and rhomboid skin And humans who need or desire to reduce or suppress skin tumors.
- ⁇ 1> An oral ultraviolet resistance improver comprising glucono- ⁇ -lactone as an active ingredient.
- Glucono- ⁇ -lactone for producing an oral ultraviolet resistance improver.
- the improvement in UV resistance is to reduce or suppress skin damage induced by UV exposure.
- the skin disorder induced by exposure to ultraviolet rays is skin inflammation or skin photoaging.
- skin damage induced by exposure to ultraviolet rays may cause skin inflammation such as erythema or edema of the skin, pigmentation, exacerbation of liver spots, sparrow eggs, etc., decrease in stratum corneum function, It is one or more types selected from a decrease in skin barrier function, a decrease in skin elasticity, a photoelasticity, a rhomboid skin, and a skin tumor.
- the use is non-therapeutic use.
- the non-therapeutic use according to ⁇ 8> which is used as a food for a sick person, a food with a functional nutrition, a health food or a food for specified health use.
- the method is a non-therapeutic method.
- the non-therapeutic method according to ⁇ 10>, wherein the oral administration or ingestion is oral administration or ingestion of a food for a sick person, a nutritional functional food, a health food or a food for specified health use.
- the subject to be administered or ingested is skin damage induced by UV exposure, for example, skin inflammation such as erythema or edema of the skin, pigmentation, exacerbation of liver spot, sparrow egg spot, etc.
- skin inflammation such as erythema or edema of the skin, pigmentation, exacerbation of liver spot, sparrow egg spot, etc.
- An animal preferably a human, in need of or wanting to reduce or suppress a decrease in stratum corneum function, a decrease in skin barrier function, a decrease in skin elasticity, a photoelasticity, a rhomboid skin, or a skin tumor.
- the subjects of administration or ingestion are humans who do not like the application of sunscreen external preparations, humans whose sunscreen external preparations do not fit the skin, and humans who are highly sensitive to ultraviolet rays. . ⁇ 14>
- the daily dose or intake per adult is 0.01 g or more, preferably 0.05 g or more, more preferably 1 g or more, more preferably 2 g or more, as glucono- ⁇ -lactone.
- the daily dose or intake per adult is 0.01 g or more, preferably 0.05 g or more, more preferably 1 g or more, more preferably 2 g or more, as glucono- ⁇ -lactone.
- the content of ⁇ 16> glucono- ⁇ -lactone is 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and still more preferably, of the total mass of the preparation.
- the oral ultraviolet resistance improver according to any one of ⁇ 1>, ⁇ 2>, and ⁇ 5> to ⁇ 7>, which is 1% by mass or more and 90% by mass or less, preferably 60% by mass or less. . ⁇ 17>
- the content of glucono- ⁇ -lactone is 0.01% by mass or more, preferably 0.1% by mass or more, more preferably 0.2%.
- ⁇ 18> The use or method according to any one of ⁇ 15> or ⁇ 17>, wherein the administration or intake is divided into 1 to 5 times a day and continuously administered or taken for 2 weeks or more.
- ⁇ 19> Use of a glucono- ⁇ -lactone in a health food for adjusting the ultraviolet resistance of the skin.
- Example 1 Effect of inhibiting UV-induced erythema and epidermis thickening
- Method HR-1 hairless mice female, 8 weeks old (Japan SLC) were allowed to freely ingest food and water during the test period, and the temperature was 23 ⁇ 1 ° C. The mice were bred under conditions of humidity 50 ⁇ 1% and illumination time 7: 00-19: 00. After one week of pre-feeding, it was divided into a control group, 0.5% glucono- ⁇ -lactone mixed group (0.5% GDL group), 1.0% glucono- ⁇ -lactone mixed group (1% GDL group), Each of the feeds having the composition shown in Table 1 was given for 2 weeks.
- the a * value is an index representing the redness of the skin color, and it can be said that the larger the a * value, the more the skin changes to red, that is, erythema occurs.
- heart blood was collected under deep anesthesia, and the UVB non-irradiated site and the skin of the irradiated site were collected, and then a HE-stained specimen was prepared and observed with a microscope.
- the average value of the skin thickness at any 15 locations per tissue was taken as the skin thickness of that tissue.
- Example 2 Expression Inhibition Effect of UV-Induced Inflammation Related Molecules, Melanin Synthesis Related Molecules, Growth Related Molecules and Dermal Degeneration Factors 1
- Method HR-1 hairless mice (female, 8 weeks old) (Japan SLC) were tested during the test period. Feed and water were ingested freely, and the animals were raised under conditions of a temperature of 23 ⁇ 1 ° C., a humidity of 50 ⁇ 1%, and a lighting time of 7: 00-19: 00. After one week of preliminary breeding, the animals were divided into a control group and a 1.0% GDL group, and each was fed a diet having the composition shown in Table 1 for 2 weeks.
- TaqMan Gene Expression Assay (Applied Biosystems) probes that specifically detect the gene of interest are Il-1b (Mm01336189_m1; IL-1b), Il-6 (Mm00446190_m1; IL-6), Gm-csf (Mm01290062_m1; GM-CSF ), Tnf (Mm00443258_m1; TNFa), Ptgs2 (Mm01307329_m1; COX-2), Tlr3 (Mm01207404_m1; TLR3), Socs3 (Mm00545913_s1; SOCS3), Vcam1 (Mm01320970_m1; VCAM-1M1, ICAM1, M3 Sele (Mm00441278_m1; E-selectin), Edn1 (Mm00438656_m1; EDN1), Kitl (Mm00442972_m1; SCF), C-kit (Mm00445212_m1; c-K
- IL-1 ⁇ Interleukin-1 ⁇
- IL-6 Interleukin-6 GM-CSF: Granulocyte macrophage colony-stimulating factor
- TNF ⁇ Tumor necrosis factor ⁇
- COX-2 Cyclooxygenase-2
- TLR3 Toll-like receptor 3
- SOCS3 Suppressor of cytokine signaling 3
- VCAM-1 Vascular cell adhesion molecule-1
- ICAM-1 Intercellular adhesion molecule-1
- E-selectin EDN1: Endothelin 1
- SCF Stem cell factor (kit-ligand)
- c-Kit LIF Leukemia inhibitory factor
- FGF2 Fibroblast growth factor 2 (basic)
- HGF Hepatocyte growth factor
- PCNA Proliferating cell nuclear antigen CyclinD1
- MMP13 Matrix metallopeptidase 13 (Collagenase 3)
- MMP2 Matrix metallopeptidase 2 (Gelatinase
- UVB irradiation increased the gene expression of IL-1 ⁇ , IL-6, GM-CSF, TNF ⁇ , COX-2, TLR3 and SOCS3. It was revealed that the expression of these inflammation-related genes was significantly suppressed at the irradiated site in the GDL group compared to the irradiated site in the control group. In addition, the expression of adhesion factors VCAM-1, ICAM-1, and E-selectin induced during inflammation was suppressed in the GDL group. When melanin synthesis-related molecules were similarly analyzed, the expression of EDN1, c-Kit, LIF, FGF2, and HGF was increased by UVB and significantly decreased in the GDL group.
- PCNA and CyclinD1 which are cell proliferation markers, was also suppressed. Suppression of expression was also observed in the GDL intake group for collagenase (MMP13), gelatinase (MMP2, MMP9), and membrane-type MMP (MMP14), which are suggested to be associated with dermal degeneration.
- Example 3 Inhibition of pigmentation by ultraviolet rays, cutaneous stratum corneum function, and skin elasticity
- HRM-2 hairless mice male, 6 weeks old) (Japan SLC), body weight, lightness (L * value) ), Redness (a * value), transdermal moisture transpiration (TEWL value), stratum corneum moisture (Capacitance) were divided into groups, and the control unirradiated group (Cont) and the control UVB irradiated group ( Cont (UVB +)) and 2.0% GDL UVB irradiation group (GDL (UVB +)). After ingesting the test sample for 3 weeks, the UVB irradiation group was irradiated with UVB once a day for 20 weeks.
- the UVB irradiation intensity was gradually increased from 40 to 130 mJ / cm 2 because UV resistance was obtained by continuous irradiation (irradiation 0 to 1 week; 40 mJ / cm 2 , irradiation 2 to 4 weeks; 54 mJ / cm 2 , Irradiation 5-7 weeks; 72 mJ / cm 2 , irradiation 8-12 weeks; 108 mJ / cm 2 , irradiation 13-14 weeks; 120 mJ / cm 2 , irradiation 15-20 weeks; 130 mJ / cm 2 ).
- the test sample was also ingested during the UVB irradiation period.
- the L * value was measured with a colorimeter
- the TEWL value was measured with a Temometer
- the stratum corneum moisture content was measured with a Corneometer.
- Example 4 Inhibitory effect 1 on UV-induced erythema and pigmentation in humans 1) Method Targeting 10 healthy males (20 to 40 years old), the same study participants are capsules containing glucono- ⁇ -lactone (daily intake of glucono- ⁇ -lactone 2000 mg) and placebo A crossover test was conducted in which the capsules were ingested continuously for 4 weeks at different times. A 4-week ingestion period was provided between the first half and the second half of the crossover. Glucono- ⁇ -lactone, a test product, was a food additive (Fuso Chemical Co., Ltd.), and each intake was taken twice a day.
- the inner side of the upper arm was irradiated with a UVB intensity of 1 mW / cm 2 while shaking the irradiation time by 7 points (irradiation area per site: 0.6 cm ⁇ 1.0 cm).
- the MED value minimum erythema amount
- 3 weeks after ingestion a dose equivalent to 2 MED was irradiated to the inner side of the upper arm within a range of 1.5 cm ⁇ 1.5 cm with a UVB intensity of 1 mW / cm 2 .
- Example 5 UV-induced erythema and pigmentation inhibitory effect 2 in humans
- Method Targeting 10 healthy males (20 to 40 years old) the same study participant is a capsule containing glucono- ⁇ -lactone and vitamins (daily intake is 2000 mg of glucono- ⁇ -lactone) , D- ⁇ -tocopherol 200 mg, L-ascorbic acid 666 mg) and placebo capsules were taken for 4 weeks continuously at different times. A 4-week ingestion period was provided between the first half and the second half of the crossover.
- Glucono- ⁇ -lactone as a test product is a food additive (Fuso Chemical Co., Ltd.), and each intake was taken twice a day.
- the inner side of the upper arm was irradiated with a UVB irradiation dose of 1 mW / cm 2 while shaking the irradiation time by 7 points (irradiation area per site: 0.6 cm ⁇ 1.0 cm).
- the MED value minimum erythema amount
- ⁇ a * values erythema intensity; difference from unirradiated sites
- ⁇ L * values degree of pigmentation; difference from unirradiated sites
- the ⁇ a * and ⁇ L * values showed the results at the UV dose that each subject defined as 1 MED at the time of placebo ingestion.
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Abstract
Description
また、近年、グルコン酸を皮膚に塗布することにより、IGF-1分泌が促進され、育毛促進、皮膚の皺、たるみの軽減等の効果を発揮することが報告されている(特許文献3)。また、グルコノ‐δ‐ラクトンをマウス皮膚に塗布することにより、皮膚表面が酸性側に傾き、角層構造が強化されバリア機能が向上すること等が報告されている(非特許文献1)。
〔特許文献2〕特開2004-229611号公報
〔特許文献3〕特開2008-100943号公報
〔非特許文献1〕Journal of investigative dermatology 2010;130:500-510
1)グルコノ-δ-ラクトンを有効成分とする経口紫外線抵抗性向上剤。
2)グルコノ-δ-ラクトンの有効量を経口投与又は摂取する、非治療的紫外線抵抗性向上方法。
3)経口紫外線抵抗性向上剤を製造するためのグルコノ-δ-ラクトンの使用。
4)グルコノ-δ-ラクトンの有効量を経口投与又は摂取する紫外線抵抗性向上方法。
従って、本発明の経口紫外線抵抗性向上剤を含む組成物は、皮膚の紫外線に対する抵抗性を向上させるための経口医薬品、医薬部外品、サプリメント又は食品となり、すなわち経口紫外線抵抗性向上剤は、経口医薬品、医薬部外品、サプリメント又は食品へ配合するための素材又は製剤として有用である。さらに、本発明の経口紫外線抵抗性向上剤を含む組成物は、紫外線暴露によって誘発される、皮膚の紅斑や浮腫等の皮膚の炎症、色素沈着の形成、肝斑や雀卵斑等の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下やそれに伴う皺の形成、日光弾性症や項部菱形皮膚、皮膚腫瘍といった皮膚障害又は光老化を軽減又は抑制するための経口医薬品、医薬部外品、サプリメント又は食品となり、すなわち経口紫外線抵抗性向上剤は、経口医薬品、医薬部外品、サプリメント又は食品へ配合するための素材又は製剤として有用である。
また、各種ビタミン類(好ましくは、ビタミンB、ビタミンC若しくはビタミンE、又はこれらの組み合わせ(例えば、ビタミンC及びE等))、アミノ酸やペプチド及びその誘導体、核酸及びその誘導体、糖類及びその誘導体、その他、カロチノイド、大豆イソフラボン、カテキン類、クロロゲン酸等の抗酸化成分等も適宜配合することができる。
また、上記製剤は、任意の投与計画に従って投与され得るが、1日1回~数回に分け、数週間~数ヶ月間継続して投与することが好ましい。例えば1日1回から10回に分け1週間以上継続して投与又は摂取することが好ましい。1日1回から5回に分け、2週間以上継続して投与又は摂取することがさらに好ましい。
また、投与又は摂取対象としては、それを必要としている若しくは希望している動物であれば特に限定されないが、紫外線暴露により誘発される皮膚障害又は光老化、例えば皮膚の紅斑や浮腫等の皮膚の炎症、色素沈着の形成、肝斑や雀卵斑等の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下やそれに伴う皺の形成、日光弾性症や項部菱形皮膚、皮膚腫瘍を軽減又は抑制を必要とする若しくは希望するヒトが挙げられる。
<1>グルコノ-δ-ラクトンを有効成分とする経口紫外線抵抗性向上剤。
<2>経口紫外線抵抗性向上剤を製造するためのグルコノ-δ-ラクトンの使用。
<3>経口紫外線抵抗性向上に使用するためのグルコノ-δ-ラクトン。
<4>グルコノ-δ-ラクトンの有効量を経口投与又は摂取する紫外線抵抗性向上方法。
<5>前記<1>~<4>において、紫外線抵抗性向上は、紫外線暴露により誘発される皮膚障害を軽減又は抑制するものである。
<6>前記<5>において、紫外線暴露により誘発される皮膚障害は、皮膚の炎症又は皮膚光老化である。
<7>前記<5>において、紫外線暴露により誘発される皮膚障害は、皮膚の紅斑や浮腫等の皮膚の炎症、色素沈着、肝斑や雀卵斑等の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症、項部菱形皮膚及び皮膚腫瘍から選ばれる1種以上である。
<8>前記<3>において、使用は非治療的使用である。
<9>病者用食品、栄養機能食品、保健食品又は特定保健用食品としての使用である、<8>記載の非治療的使用。
<10>前記<4>において、方法は非治療的方法である。
<11>経口投与又は摂取が、病者用食品、栄養機能食品、保健食品又は特定保健用食品の経口投与又は摂取である、<10>記載の非治療的方法。
<12>前記<4>において、投与又は摂取の対象は、紫外線暴露により誘発される皮膚障害、例えば皮膚の紅斑や浮腫等の皮膚の炎症、色素沈着、肝斑や雀卵斑等の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症、項部菱形皮膚、又は皮膚腫瘍を軽減又は抑制を必要とする若しくは希望する動物、好ましくはヒトである。
<13>前記<4>において、投与又は摂取の対象は、日焼け止め外用剤の塗布を好まないヒト、日焼け止め外用剤が肌に合わない体質のヒト、紫外線に対して感受性の高いヒトである。
<14>成人1人当たりの1日の投与量又は摂取量を、グルコノ-δ-ラクトンとして0.01g以上、好ましくは0.05g以上であり、より好ましくは1g以上であり、更に好ましくは2g以上であり、そして10g以下であり、好ましくは5g以下とするために用いる、<1>又は<2>に記載の経口紫外線抵抗性向上剤。
<15>成人1人当たりの1日の投与量又は摂取量が、グルコノ-δ-ラクトンとして0.01g以上、好ましくは0.05g以上であり、より好ましくは1g以上であり、更に好ましくは2g以上であり、そして10g以下であり、好ましくは5g以下である、<3>及び<5>~<9>のいずれかに記載の使用、又は<4>~<7>及び<10>~<13>のいずれかに記載の方法。
<16>グルコノ-δ-ラクトンの含有量が、製剤全質量の0.01質量%以上、好ましくは0.1質量%以上であり、より好ましくは0.5質量%以上であり、さらに好ましくは1質量%以上であり、そして90質量%以下、好ましくは60質量%以下である、<1>、<2>、及び<5>~<7>のいずれかに記載の経口紫外線抵抗性向上剤。
<17><9>又は<11>に記載の食品において、グルコノ-δ-ラクトンの含有量が、0.01質量%以上、好ましくは0.1質量%以上であり、より好ましくは0.2質量%以上であり、更に好ましくは0.4質量%以上であり、そして50質量%以下であり、好ましくは20質量%以下であり、更に好ましくは10質量%以下である、使用又は方法。
<18>投与又は摂取が、1日1回から5回に分け、2週間以上継続して投与又は摂取することである、<15>又は<17>のいずれかに記載の使用又は方法。
<19>グルコノ-δ-ラクトンの皮膚の紫外線抵抗性を調整するための保健食品における使用。
<20>グルコノ-δ-ラクトンの皮膚の紫外線抵抗性を調整するための保健食品製造における使用。
1)方法
HR-1ヘアレスマウス(雌性、8週齢)(日本SLC)に、試験期間中、飼料および水を自由摂取させ、温度23±1℃、湿度50±1%、照明時間7:00-19:00の条件下で飼育した。1週間の予備飼育後、コントロール群、0.5%グルコノ-δ-ラクトン混餌群(0.5%GDL群)、1.0%グルコノ-δ-ラクトン混餌群(1%GDL群)に分け、それぞれ表1記載の組成の餌を2週間与えた。摂取2週後に、ペントバルビタール麻酔下にて、マウス背部に1.5cm×1.0cmの部位を近接して2ヶ所(照射部位及び未照射部位)設定し、照射部位には1mW/cm2のUVB照射線量で、40秒間(40mJ/cm2)照射した。照射2日後の紅斑の程度を、分光式色差計SE-6000(日本電色工業)を用いた皮膚色(a*値)測定により評価した。a*値は皮膚色の赤味を表す指標であり、a*値が大きいほど皮膚が赤色に変化、すなわち紅斑が生じていると言える。
測定後、深麻酔下で心採血し、UVB未照射部位および照射部位の皮膚を採取した後、HE染色標本を作製し、顕微鏡で観察した。表皮厚は1組織当たり、任意の15ヶ所の表皮厚の平均値をその組織の表皮厚とした。得られた値はAve.±S.D.、n=8で示し、多群間の統計学的有意差検定はDunnettによる多重比較検定を行った(*p<0.05, **p<0.01(vs GDL(-) UVB(+))。
結果を図1に示した。GDL群ではUVB照射によるa*値の上昇を濃度依存的に抑制し、1%GDL群の照射部位ではコントロール群の照射部位に比べ有意なa*値の抑制が認められた。また、コントロール群の照射部位と比較してGDL群の照射部位では、有意に表皮肥厚が抑制された。以上のことから、GDLは紫外線抵抗性向上作用を有することが明らかとなった。
1)方法
HR-1ヘアレスマウス(雌性、8週齢)(日本SLC)に、試験期間中、飼料および水を自由摂取させ、温度23±1℃、湿度50±1%、照明時間7:00-19:00の条件下で飼育した。1週間の予備飼育後、コントロール群、1.0%GDL群に分け、それぞれ表1記載の組成の餌を2週間与えた。摂取2週後に、ペントバルビタール麻酔下にて、マウス背部に1.5cm×1.0cmの部位を近接して2ヶ所(照射部位及び未照射部位)設定し、照射部位には1mW/cm2のUVB照射線量で、40秒間(40mJ/cm2)照射した。照射24時間後に心採血し、UVB未照射部位および照射部位の皮膚を採取し、RNAを抽出した。抽出したRNAからqRT-PCRにより下記に示す分子の遺伝子発現量を定量した。目的の遺伝子を特異的に検出するTaqMan Gene Expression Assay (Applied Biosystems)プローブはIl-1b(Mm01336189_m1; IL-1b)、Il-6(Mm00446190_m1; IL-6)、Gm-csf(Mm01290062_m1; GM-CSF)、Tnf(Mm00443258_m1; TNFa)、Ptgs2(Mm01307329_m1; COX-2)、Tlr3(Mm01207404_m1; TLR3)、Socs3(Mm00545913_s1; SOCS3)、Vcam1(Mm01320970_m1; VCAM-1)、Icam1(Mm00516023_m1; ICAM-1)、Sele(Mm00441278_m1; E-selectin)、Edn1(Mm00438656_m1; EDN1)、Kitl(Mm00442972_m1; SCF)、C-kit(Mm00445212_m1; c-Kit)、Lif(Mm00434761_m1; LIF)、Fgf2(Mm00433287_m1; FGF2)、Hgf(Mm01135185_m1; HGF)、Pcna(Mm00448100_g1; PCNA)、Ccnd1(Mm00432359_m1; CyclinD1)、Mmp13(Mm00439491_m1; MMP13)、Mmp2(Mm00439506_m1; MMP2)、Mmp9(Mm00442991_m1; MMP9)、Mmp14(Mm00485054_m1; MMP14)を用いた。目的遺伝子発現量は内部標準遺伝子Rplp0(Mm01974474_gH; RPLP0)の発現量で補正した。解析には7500 Fast Real-Time PCR System (Applied Biosystems)を用いた。得られた値はAve.±S.D.、n=10で示し、多群間の統計学的有意差検定はDunnettによる多重比較検定を行った(*p<0.05, **p<0.01(vs Cont UVB+))。
IL-6:Interleukin-6
GM-CSF:Granulocyte macrophage colony-stimulating factor
TNFα:Tumor necrosis factor α
COX-2:Cyclooxygenase-2
TLR3:Toll-like receptor 3
SOCS3:Suppressor of cytokine signaling 3
VCAM-1:Vascular cell adhesion molecule-1
ICAM-1:Intercellular adhesion molecule-1
E-selectin
EDN1:Endothelin 1
SCF:Stem cell factor (kit-ligand)
c-Kit
LIF:Leukemia inhibitory factor
FGF2:Fibroblast growth factor 2 (basic)
HGF:Hepatocyte growth factor
PCNA:Proliferating cell nuclear antigen
CyclinD1
MMP13: Matrix metallopeptidase 13 (Collagenase 3)
MMP2: Matrix metallopeptidase 2 (Gelatinase A)
MMP9: Matrix metallopeptidase 9 (Gelatinase B)
MMP14:Matrix metallopeptidase 14 (membrane-inserted)
結果を図2~6に示した。UVB照射によりIL-1β,IL-6,GM-CSF,TNFα,COX-2,TLR3,SOCS3の遺伝子発現が上昇した。GDL群の照射部位ではコントロール群の照射部位に比べ、これら炎症関連遺伝子の発現が有意に抑制されることが明らかとなった。また炎症時に誘導される接着因子VCAM-1,ICAM-1,E-selectinもGDL群では発現抑制が認められた。メラニン合成関連分子も同様に発現解析を行ったところ、EDN1,c-Kit,LIF,FGF2,HGFの発現がUVBによって上昇し、GDL群では有意に低下することが明らかとなった。更に、細胞の増殖マーカーであるPCNAやCyclinD1の発現も抑制された。真皮変性との関連が示唆されているコラゲナーゼ(MMP13),ゼラチナーゼ(MMP2,MMP9)、膜型MMP(MMP14)についてもGDL摂取群で発現の抑制が認められた。
1)方法
HRM-2ヘアレスマウス(雄性、6週齢)(日本SLC)を用い、体重、明度(L*値)、赤色度(a*値)、経皮水分蒸散量(TEWL値)、角層水分量(Capacitance)が均等になるように群分けし、コントロール未照射群(Cont)、コントロールUVB照射群(Cont(UVB+))、2.0%GDL UVB照射群(GDL(UVB+))の3群とした。試験試料を3週間前摂取させた後、UVB照射群には1日1回、20週間、UVBを照射した。連続照射により紫外線抵抗性が付くためUVB照射強度は40から130mJ/cm2へと段階的に上げていった(照射0~1週;40mJ/cm2、照射2~4週;54mJ/cm2、照射5~7週;72mJ/cm2、照射8~12週;108mJ/cm2、照射13~14週;120mJ/cm2 、照射15~20週;130mJ/cm2)。なお、UVB照射期間中も試験試料を摂取させた。群分け時と、照射0、4、8、12、16、20週目に、色差計でL*値、TewameterでTEWL値、Corneometerで角層水分量(Capacitance値)の測定を行った。また、照射20週目にCutometerで皮膚物性パラメータを測定した。得られた値はAve.±S.D.、n=10-11で示し、Tukey-Kramerによる多重比較検定を行った。
結果を図7~10に示した。UV照射8または12週目以降に置いて、GDL摂取により、UVB照射によるL*値低下、TEWL値上昇、角層水分量(Capacitance値)低下を抑制した。さらに、皮膚の粘弾性(Uv/Ue)の低下を抑制した。以上よりGDLは、長期反復紫外線照射によって生じる種々の皮膚障害を抑制することが明らかとなった。
1)方法
健常男性10名(20~40歳代)を対象とし、同一の試験参加者がグルコノ-δ-ラクトンを含有するカプセル剤(1日の摂取量がグルコノ-δ-ラクトン2000mg)とプラセボカプセル剤を、時期を変えて4週間連続摂取するクロスオーバー試験を行った。クロスオーバー前半と後半の間に4週間の摂取休止期間を設けた。被験品であるグルコノ-δ-ラクトンは食品添加物(扶桑化学工業)であり、各摂取量 を1日2回に分けて摂取した。摂取3週後において、上腕内側部に1mW/cm2のUVB強度で照射時間を7点振って照射した(1部位当たりの照射面積0.6cm×1.0cm)。UVB照射24時間後に、目視によりMED値(最小紅斑量)を判定した。
また、摂取3週後に、上腕内側部に1.5cm×1.5cmの範囲で1mW/cm2のUVB強度で2MED相当の線量を照射した。UVB照射24時間後に、色差計を用いてΔa*値(紅斑強度;未照射部位との差)を測定した。さらに、UVB照射1週後に、各照射部位について、色差計を用いてΔL*値(色素沈着度;未照射部位との差)を測定した。得られた値はAve.±S.D.、n=10で示し、2群間の統計学的有意差検定はpaired t-testを行った(*p<0.05,**p<0.01)。
結果を図11に示した。GDL群は、プラセボ群に比べMED値が有意に高く、紫外線抵抗性が向上していることが明らかとなった。実際に、UVB照射24時間後のΔa*値は、プラセボ群と比べてGDL群において有意に低下しており、紫外線誘導性の紅斑形成を抑制した。また、UVB照射1週間後のΔL*値も、プラセボ群と比較してGDL群において有意に低下し、色素沈着を抑制していることが明らかとなった。
1)方法
健常男性10名(20~40歳代)を対象とし、同一の試験参加者がグルコノ-δ-ラクトン、ビタミン類を含有するカプセル剤(1日の摂取量がグルコノ-δ-ラクトン2000mg、d-α-トコフェロール200mg、L-アスコルビン酸666mg)とプラセボカプセル剤を、時期を変えて4週間連続摂取するクロスオーバー試験を行った。クロスオーバー前半と後半の間に4週間の摂取休止期間を設けた。被験品であるグルコノ-δ-ラクトンは食品添加物(扶桑化学工業)であり、各摂取量を1日2回に分けて摂取した。摂取3週後において、上腕内側部に1mW/cm2のUVB照射線量で照射時間を7点振って照射した(1部位当たりの照射面積0.6cm×1.0cm)。
UVB照射24時間後に、目視によりMED値(最小紅斑量)を判定し、各照射部位について、写真撮影と色差計を用いてΔa*値(紅斑強度;未照射部位との差)を測定した。さらに、UVB照射1週後に、各照射部位について、写真撮影と色差計を用いてΔL*値(色素沈着度;未照射部位との差)を測定した。Δa*値とΔL*値は、各被験者がプラセボ摂取時に1MEDと定めたUV線量における結果を示した。得られた値はAve.±S.D.、n=10で示し、2群間の統計学的有意差検定はpaired t-testを行った(*p<0.05,**p<0.01)。
結果を図12に示した。GDL群は、プラセボ群に比べMED値が有意に高く、紫外線抵抗性が向上していることが明らかとなった。実際に、UVB照射24時間後のΔa*値は、プラセボ群と比べてGDL群において有意に低下しており、紫外線誘導性の紅斑形成を抑制した。また、UVB照射1週間後のΔL*値も、プラセボ群と比較してGDL群において有意に低下し、色素沈着を抑制していることが明らかとなった。
Claims (16)
- グルコノ-δ-ラクトンを有効成分とする経口紫外線抵抗性向上剤。
- 紫外線暴露により誘発される皮膚障害を軽減又は抑制する請求項1記載の経口紫外線抵抗性向上剤。
- 紫外線暴露により誘発される皮膚障害が、皮膚の炎症又は皮膚老化である請求項2記載の経口紫外線抵抗性向上剤。
- 紫外線暴露により誘発される皮膚障害が、皮膚の紅斑、浮腫等の炎症、色素沈着、肝斑や雀卵斑の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症及び皮膚腫瘍から選ばれる1種以上である請求項2記載の経口紫外線抵抗性向上剤。
- グルコノ-δ-ラクトンの有効量を経口投与又は摂取する、非治療的紫外線抵抗性向上方法。
- 紫外線暴露により誘発される皮膚障害を軽減又は抑制する、請求項5記載の非治療的紫外線抵抗性向上方法。
- 紫外線暴露により誘発される皮膚障害が、皮膚の炎症又は皮膚老化である、請求項6記載の非治療的紫外線抵抗性向上方法。
- 紫外線暴露により誘発される皮膚障害が、皮膚の紅斑、浮腫等の炎症、色素沈着、肝斑又は雀卵斑の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症及び皮膚腫瘍から選ばれる1種以上である請求項6記載の非治療的紫外線抵抗性向上方法。
- 経口紫外線抵抗性向上剤を製造するためのグルコノ-δ-ラクトンの使用。
- 経口紫外線抵抗性向上剤が、紫外線暴露により誘発される皮膚障害を軽減又は抑制するものである請求項9記載の使用。
- 紫外線暴露により誘発される皮膚障害が、皮膚の炎症又は皮膚老化である請求項10記載の使用。
- 紫外線暴露により誘発される皮膚障害が、皮膚の紅斑、浮腫等の炎症、色素沈着、肝斑や雀卵斑の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症及び皮膚腫瘍から選ばれる1種以上である請求項10記載の使用。
- グルコノ-δ-ラクトンの有効量を経口投与又は摂取する紫外線抵抗性向上方法。
- 紫外線暴露により誘発される皮膚障害を軽減又は抑制する請求項13記載の方法。
- 紫外線暴露により誘発される皮膚障害が、皮膚の炎症又は皮膚老化である請求項14記載の方法。
- 紫外線暴露により誘発される皮膚障害が、皮膚の紅斑、浮腫等の炎症、色素沈着、肝斑や雀卵斑の増悪化、角層機能の低下、皮膚バリア機能の低下、皮膚弾力性の低下、日光弾性症及び皮膚腫瘍から選ばれる1種以上である請求項14記載の方法。
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JP2020522546A (ja) * | 2017-06-06 | 2020-07-30 | サミ ラブズ リミテッド | Bacillus coagulans由来細胞外代謝産物のスキンケア用途 |
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US20160136130A1 (en) | 2016-05-19 |
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