WO2011083738A1 - 経口用のdna損傷修復促進剤及びエラスターゼ活性抑制剤 - Google Patents
経口用のdna損傷修復促進剤及びエラスターゼ活性抑制剤 Download PDFInfo
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- WO2011083738A1 WO2011083738A1 PCT/JP2010/073796 JP2010073796W WO2011083738A1 WO 2011083738 A1 WO2011083738 A1 WO 2011083738A1 JP 2010073796 W JP2010073796 W JP 2010073796W WO 2011083738 A1 WO2011083738 A1 WO 2011083738A1
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- bifidobacterium
- bacterium
- dna damage
- elastase activity
- ultraviolet rays
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Images
Classifications
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
-
- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
-
- 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
- A61P17/18—Antioxidants, e.g. antiradicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
-
- 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 DNA damage repair promoter and an elastase activity inhibitor.
- DNA damage is caused by a variety of external or internal factors and occurs on a daily basis. However, neglecting DNA damage not only inhibits important functions such as replication and transcription, but can also cause cancer, aging, and the like by causing mutations. Therefore, the living body universally repairs DNA damage by various repair mechanisms corresponding to the type of DNA damage, and maintains genome information and its function. Representative examples of this repair mechanism include a homologous recombination repair mechanism for DNA double-strand breaks, a base excision repair mechanism for oxidative base damage by reactive oxygen species, a nucleotide excision repair mechanism for pyrimidine dimers generated by ultraviolet rays, There is a mismatch repair mechanism for replication errors.
- the repair mechanism is abnormal, the function is reduced, or the damage exceeds the repair capability.
- the cells are prone to death due to apoptosis, and a mutation is induced to promote long-term processes such as canceration and aging.
- DNA damage suppression and DNA damage repair are different, and DNA damage suppression caused by the above carcinogenic substances can be achieved by adsorbing orally ingested bacteria on the surface of the digestive tract or carcinogenic substances. It is thought that it does not promote the repair of DNA damage because it suppresses contact and absorption of various carcinogenic substances administered orally by adsorbing to and excreting bacterial cells. .
- DNA damage caused by ultraviolet rays is caused by the formation of cyclobutane pyrimidine dimers, 6-4 type photoproducts, etc. in skin cells by exposure to ultraviolet rays, and an increase in the amount of ultraviolet rays due to ozone layer destruction in recent years. Development of prevention / suppression of the DNA damage is being promoted.
- a method for preventing DNA damage a method of absorbing or scattering ultraviolet rays with a sunscreen agent or the like is known.
- this method can only reduce skin damage caused by ultraviolet rays, and DNA damage is caused by exposure to ultraviolet rays. If it does, it cannot promote the repair of the damage.
- a cosmetic composition that suppresses DNA damage caused by UV exposure a plant comprising a first component comprising an inactivated culture of Bifidobacterium, a glycoprotein, a carbohydrate polymer, and an arabinogalactan protein
- a topical cosmetic composition for combating UV radiation-induced skin damage comprising a second component that is an extract of an extracellular matrix (Patent Document 1).
- the dermal extracellular matrix component includes collagen, elastin, glycosaminoglycan, and the like. Of these, elastin is the main protein of elastic fibers.
- the elastase activity inhibition of the fermented product was evaluated by an in vitro test performed by adding a test substance to an elastase derived from human neutrophils or an elastase derived from porcine pancreas, and the inhibition of elastase activity was performed in an in vivo test. It has not been confirmed. In order for substances actually applied to the skin to exert an elastase activity inhibitory action, it is necessary for the active ingredient to pass through the stratum corneum and epidermis to reach the dermis layer, so this action in vivo was confirmed. An elastase activity inhibitor has been desired.
- An object of the present invention is to provide an oral DNA damage repair promoter and an oral elastase activity inhibitor.
- the present inventors examined the promotion of repair of DNA damage and the suppression of elastase activity. Surprisingly, the ingestion of Bifidobacterium bacteria can promote the repair of DNA damage and the activity of elastase It was found that it can be suppressed.
- the present invention provides an oral DNA damage repair promoter containing Bifidobacterium as an active ingredient.
- the present invention provides an oral cyclobutane pyrimidine dimer amount reduction accelerator containing a Bifidobacterium bacterium as an active ingredient.
- the present invention provides an oral elastase activity inhibitor containing a Bifidobacterium bacterium as an active ingredient.
- the present invention provides an elastase activity inhibitor as described in iii) above, which is a skin aging preventive / improving agent.
- the present invention provides a method for promoting DNA damage repair, which comprises orally administering a Bifidobacterium bacterium.
- the present invention provides a method for promoting a decrease in the amount of cyclobutane pyrimidine dimer, which comprises orally administering a Bifidobacterium bacterium.
- the present invention provides a method for inhibiting elastase activity, which comprises orally administering a Bifidobacterium bacterium.
- the present invention provides the method described in vii) above, which is a method for preventing and improving skin aging.
- the present invention provides a Bifidobacterium genus used for promoting repair of DNA damage by oral administration.
- the present invention provides a Bifidobacterium genus used for promoting reduction of the amount of cyclobutane pyrimidine dimer by oral administration.
- the present invention provides a Bifidobacterium bacterium used for suppressing elastase activity by oral administration.
- the present invention provides the bacterium described in the above xi), which is used for preventing and improving skin aging.
- the present invention provides the use of a Bifidobacterium bacterium for producing an oral DNA damage repair promoter.
- the present invention provides the use of a bacterium belonging to the genus Bifidobacterium for the production of an oral cyclobutane pyrimidine dimer reduction promoter.
- the present invention provides the use of a Bifidobacterium bacterium for producing an oral elastase activity inhibitor.
- the present invention provides the use described in xv) above, which is for producing a skin aging prevention / amelioration agent.
- the DNA damage repair promoter for oral use of the present invention is useful as a pharmaceutical, food or drink for promoting repair of DNA damage.
- the activity of elastase can be suppressed by oral administration. Therefore, the elastase activity inhibitor for oral use of the present invention is useful as a pharmaceutical, food or drink for preventing / improving skin aging.
- the active ingredients of the oral DNA damage repair promoter (hereinafter also referred to as DNA damage repair promoter) and oral elastase activity inhibitor (hereinafter also referred to as elastase activity inhibitor) of the present invention are Bifidobacterium bacteria. is there. Such Bifidobacterium is first described.
- Bifidobacterium bacteria e.g., Bifidobacterium breve (Bifidobacterium breve), Bifidobacterium bifidum (Bifidobacterium bifidum), Bifidobacterium longum (Bifidobacterium longum), Bifidobacterium address Sen Eustis (Bifidobacterium adolescentis), Bifidobacterium Katenuratamu (Bifidobacterium catenulatum), Bifidobacterium shoe de catheter Marne-la-Tam (Bifidobacterium pseudocatenulatum), Bifidobacterium animalis (Bifidobacterium Nimalis) and the like, may be one or two or more of these species. Among these, Bifidobacterium breve is preferable from the viewpoint of DNA damage repair promoting action and elastase activity suppressing action.
- Bifidobacterium breve YIT4063 (FERM BP-2823), Bifidobacterium breve YIT 4064 (FERM BP-2824), Bifidobacterium breve YIT 4065 (FERM BP).
- Bifidobacterium breve YIT 12272 (FERM ABP-11320, National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center (address: 305-1856, East 1 Tsukuba, Ibaraki, Japan) 1 chome Deposited with the February 16, 2010 in the Central 6)
- offspring strains that the parent strain these Bifidobacterium breve is preferable.
- Bifidobacterium breve YIT 4065 and Bifidobacterium breve YIT 12272 are particularly preferable from the viewpoint of DNA damage repair promoting action and elastase activity suppressing action.
- the “offspring strain” is a concept including a natural mutant, a mutant by mutation treatment, a mutant by genetic manipulation, and the like.
- the Bifidobacterium genus bacterium may be either a bacterial cell (live cell) or a processed product of the bacterial cell.
- the treated product is not particularly limited as long as it can be obtained by a conventional treatment.
- a heated cell dead cell
- a freeze-dried product thereof a culture containing them
- a super Crushing liquid by sonic wave bacterial enzyme treatment liquid
- solid residue separated by solid-liquid separation means such as filtration or centrifugation
- treatment liquid from which cell wall has been removed by enzyme or mechanical means concentrate of the treatment liquid Nucleic acid-containing fractions obtained by dissolving bacteria with a surfactant and then precipitating with ethanol, etc .
- bacterial cells live cell
- dead cell a heated cell
- freeze-dried product thereof a disrupted solution of bacteria by ultrasonic waves
- bacterial enzyme treatment solution a bacterial enzyme treatment solution
- bacterial cells (live bacteria) and the above lyophilized product are particularly preferred from the viewpoint of DNA damage repair promoting action and elastase activity inhibiting action.
- the dead cells can be obtained, for example, by heat treatment, treatment with drugs such as antibiotics, treatment with chemical substances such as formalin, treatment with ultraviolet rays, treatment with radiation such as ⁇ rays.
- promoting DNA damage repair means promoting repair of damaged DNA molecules.
- the Bifidobacterium genus bacterium of the present invention promotes a decrease in the amount of cyclobutane pyrimidine dimer (hereinafter also referred to as CPD) by oral administration, and thus has an excellent repair promoting action against DNA damage. . Therefore, Bifidobacterium can be used as a DNA damage repair promoter, and can be used to produce a DNA damage repair promoter.
- Bifidobacterium bacteria can also be a preventive or therapeutic agent for cancer or aging. It is useful as a human or veterinary drug, quasi-drug, food or drink, pet food, etc. for preventing / treating cancer or aging.
- the DNA damage repair promoter of the present invention can promote the repair of DNA damage caused by exposure to ultraviolet rays, Bifidobacterium bacteria can be a preventive / therapeutic agent for skin cancer or skin aging.
- the Bifidobacterium genus bacteria of this invention have the CPD amount fall promotion effect. Therefore, the Bifidobacterium genus bacterium can be used as a CPD amount reduction promoter, and can be used to produce a CPD amount reduction promoter.
- the CPD reduction promoter of the present invention reduces the amount of CPD, which is an indicator of DNA damage. Therefore, Bifidobacterium can also be a preventive / therapeutic agent for cancer or aging, and CPD is produced by exposure to ultraviolet rays. Therefore, the CPD amount reduction promoting agent of the present invention is particularly useful as a preventive / therapeutic agent for skin cancer or skin aging.
- the “elastase activity inhibitor” of the present invention will be described in detail.
- the Bifidobacterium of the present invention has an action of suppressing the elastase activity in the skin enhanced by exposure to ultraviolet rays by oral administration. Therefore, Bifidobacterium bacteria can be used as an elastase activity inhibitor, and can be used to produce an elastase activity inhibitor.
- Bifidobacterium bacteria can also be a skin aging prevention and improvement agent, and the above elastase activity inhibitor prevents skin aging -It is useful as a human or veterinary drug, quasi drug, food or drink, pet food, etc. for improvement.
- Skin aging prevention / improvement includes prevention and improvement of skin wrinkles, sagging prevention, elasticity improvement, and anti-aging.
- the dosage form of the DNA damage repair promoter, elastase activity inhibitor and skin aging preventive / ameliorating agent is oral administration.
- the administration may be performed before, during or after UV exposure. Among these, it is preferable to administer at least before UV exposure, and more preferably before UV exposure and during UV exposure from the viewpoint of DNA damage repair promoting action, elastase activity suppressing action and skin aging prevention / amelioration action.
- the administration period before the exposure is preferably 5 days or more, preferably 5 to 10 days from the viewpoint of DNA damage repair promoting action, elastase activity inhibiting action and skin aging preventing / ameliorating action. More preferred.
- an effect of promoting DNA damage repair, an effect of suppressing elastase activity, and an effect of preventing and improving skin aging can be expected.
- Examples of dosage forms of orally administered preparations when DNA damage repair promoters, elastase activity inhibitors and skin aging prevention / improving agents are used as pharmaceuticals include, for example, tablets, capsules, granules, dragees, pills, fine granules Agents, powders, powders, sustained-release preparations, suspensions, emulsions, syrups, lyophilizers, liquids, elixirs and the like.
- the above-mentioned preparation can be produced by a conventional method, and Bifidobacterium genus bacteria may be used alone or in combination with a pharmaceutically acceptable carrier.
- the carrier include an excipient, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a corrigent, a coloring agent, a fragrance, a diluent, a bactericidal agent, an osmotic pressure adjusting agent, and a pH.
- binder examples include starch, dextrin, gum arabic powder, gelatin, methyl cellulose, hydroxypropyl cellulose, crystalline cellulose, ethyl cellulose, polyvinyl pyrrolidone, macrogol and the like.
- disintegrant examples include hydroxypropyl starch, sodium carboxymethylcellulose, carboxymethylcellulose calcium, carboxymethylcellulose, and low-substituted hydroxypropylcellulose.
- Examples of the surfactant include sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80, and the like.
- Examples of the lubricant include talc, waxes, hydrogenated vegetable oil, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol and the like.
- Examples of the fluidity promoter include light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate, and the like.
- diluent examples include distilled water for injection, physiological saline, aqueous glucose solution, olive oil, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol and the like.
- the DNA damage repair promoter, elastase activity inhibitor and skin aging prevention / improving agent of the present invention are not only used as pharmaceuticals as described above, but also used as foods, quasi drugs, pet foods, and the like. it can.
- the above-mentioned Bifidobacterium genus bacteria may be contained in the food or drink as it is or with various nutritional components added. This food and drink can be used as a health food or food material useful for preventing or treating cancer or aging, or a health food or food material useful for preventing or improving skin aging. May be labeled with the above effect.
- additives that can be used as foods and drinks are used as appropriate, and forms suitable for food using conventional means
- it may be formed into granules, granules, tablets, capsules, pastes, etc., and various foods such as processed meat products such as ham and sausage, fishery processed products such as kamaboko and chikuwa; bread, confectionery, It may be used by adding to butter, milk powder, fermented food or drink, or may be used by adding to beverages such as water, fruit juice, milk, soft drinks and tea drinks.
- fermented products such as fermented milk, lactic acid bacteria beverages, fermented soymilk, fermented fruit juice, fermented plant liquid, and the like containing Bifidobacterium as an active ingredient are preferable.
- manufacture of these fermented food-drinks can be manufactured in accordance with a conventional method.
- fermented milk is obtained by inoculating and culturing Bifidobacterium in a sterilized milk medium and homogenizing it to obtain a fermented milk base. Subsequently, a separately prepared syrup solution is added and mixed, homogenized with a homogenizer or the like, and flavor is further added to obtain a final product.
- the fermented milk thus obtained can be a product of any form such as a plain type, a soft type, a fruit flavor type, a solid form, and a liquid form.
- the number of Bifidobacterium is preferably 1 ⁇ 10 3 CFU or more per day, more preferably 1 ⁇ 10 3 to 1 ⁇ 10 13 CFU per day. An amount containing 1 ⁇ 10 6 to 1 ⁇ 10 10 CFU as a daily dose is particularly preferable.
- the wavelength of the ultraviolet light is not particularly limited, but ultraviolet light having a wavelength of 280 to 400 nm is likely to cause skin cancer and skin aging because it has a high rate of causing DNA damage, and more elastase activity is obtained. Therefore, the DNA damage repair promoter, elastase activity inhibitor and skin aging preventive / ameliorating agent of the present invention are DNAs produced by exposure to ultraviolet rays having a wavelength of 280 to 400 nm. It is suitably used as a damage repair accelerator, an inhibitor of increased elastase activity, and a skin aging preventive / ameliorating agent.
- the UV dose is not particularly limited, 20 mJ / cm 2 or more per day, especially when it is 40 mJ / cm 2 or more, repair promoting agents DNA damage present invention, anti-elastase activity inhibitors and skin aging An improver is preferably used.
- the DNA damage repair promoter and cyclobutane pyrimidine dimer amount decrease promoter of the present invention are used in conventional intravenous injections or the like because they are used orally with abundant dietary experience. Compared with a cancer chemotherapeutic agent that has been accompanied by various side effects, its safety is extremely high, and the burden on the subject can be remarkably reduced.
- Example 1 (Preparation of bacterial cell solution) A medium having the following composition, modified from the medium of Rogosa et al. (Eftymiou C. et al., J infect dis., 110, 258-267, 1962), was sterilized by heating at 121 ° C. for 15 minutes. This medium was inoculated with 1 v / v% of Bifidobacterium breve YIT 4065 strain (FERM BP-6223) and cultured anaerobically at 37 ° C. for about 20 hours to obtain a culture solution. The culture solution was centrifuged at 3500 ⁇ G to collect Bifidobacterium bacteria. It was suspended in physiological saline so that the cells to 1.0 ⁇ 10 10 CFU / mL, to give a cell solution.
- Test Example 1 CPD amount measurement test
- HR-1 6 weeks old
- HR-1 6 weeks old
- the first group, the third group, the fifth group and the seventh group (hereinafter also referred to as a control group) are given physiological saline
- the second group, the fourth group, the sixth group and the eighth group (Hereinafter also referred to as the bacterial cell group)
- the bacterial cell solution prepared in Example 1 was orally administered for 0.1 days / day for 9 days.
- the first group and the second group were not irradiated with ultraviolet rays
- the third to eighth groups were irradiated with the ultraviolet irradiation device (Toshiba SE-FL-20 for 4 days from the sixth day after the start of administration).
- the ultraviolet irradiation device (Toshiba SE-FL-20 for 4 days from the sixth day after the start of administration).
- ) was irradiated with 40 mJ / cm 2 of ultraviolet rays containing 280 to 400 nm per day.
- 24 hours after the last administration for the first group and the second group 6 hours after the last irradiation for the third group and the fourth group, and 12 hours after the last irradiation for the fifth group and the sixth group.
- the dorsal skin was collected 24 hours after the last irradiation.
- UV + indicates that UV irradiation has been performed
- UV- indicates that UV irradiation has not been performed.
- Genomic DNA was purified from each collected back skin (QIAamp (registered trademark) DNA mini kit), a fixed amount was coated on a 96-well plate, and cyclobutane pyrimidine dimer antibody (TDM-2) was bound thereto, followed by biotin.
- the signal was amplified with a labeled secondary antibody and enzyme-labeled streptavidin, and finally a substrate was added for coloration, and the absorbance at 492 nm was measured (ELISA method). The measurement results are shown in FIG.
- Example 2 (Preparation of bacterial cell sample) 1.5 L of a medium prepared using mineral liquid (1 w / v%), yeast extract (1 w / v%), lactose (3 w / v%) and milk protein (5 w / v%) in 2 L Kolben, Sterilized by heating at 121 ° C. for 15 minutes.
- This medium is inoculated with 1 v / v% of Bifidobacterium breve YIT 12272 strain (FERM ABP-11320) and cultured anaerobically at 36 ° C. for about 20 hours while maintaining the pH at 5.5 with sodium hydroxide. To obtain a culture solution.
- This culture solution was centrifuged at 15,000 ⁇ G to collect Bifidobacterium bacteria.
- the composition of the mineral liquid is potassium (I) phosphate (10 w / v%), potassium (II) phosphate (20 w / v%), sodium acetate (30 w / v%) and ammonium sulfate (30 w / v%). ).
- 100 mL of a dispersion liquid in which 8 w / v% milk protein and 4 w / v% sugar were dispersed was prepared and sterilized by heating at 121 ° C. for 15 minutes.
- Test Example 2 Hairless mice Hos: HR-1 (6 weeks old) were acclimated for 1 week after delivery, and then 3 mice were divided into a total of 3 groups. Among the mouse groups, physiological saline was orally administered to the first group and the second group, and the bacterial cell sample prepared in Example 2 was orally administered to the third group for 9 days at 0.1 mL / day. In addition, UV irradiation was not performed for the first group, and for the second and third groups, the UV irradiation apparatus (Toshiba SE-FL-20) was used together with the administration for 6 days from the start of the administration for 4 days.
- Toshiba SE-FL-20 the UV irradiation apparatus
- Ultraviolet rays containing 280 to 400 nm were irradiated at 50 mJ / cm 2 per day, and then the back skin was collected.
- physiological saline is administered and the mice that are not irradiated with ultraviolet rays are defined as blank groups
- physiological saline is administered
- the mice that are irradiated with ultraviolet rays are defined as control groups
- the bacterial cell sample is administered.
- a group of mice irradiated with ultraviolet rays was defined as a bacterial cell group (Table 2).
- UV + indicates that UV irradiation is performed
- UV- indicates that UV irradiation is not performed.
- Genomic DNA was purified from each collected back skin (QIAamp (registered trademark) DNA mini kit), a fixed amount was coated on a 96-well plate, and cyclobutane pyrimidine dimer antibody (TDM-2) was bound thereto, followed by biotin labeling.
- the signal was amplified with a secondary antibody and enzyme-labeled streptavidin, and finally the substrate was added to color and the absorbance at 492 nm was measured (ELISA method). The measurement results are shown in FIG.
- Example 3 (Preparation of bacterial cell sample) 1.5 L of a medium prepared using mineral liquid (1 w / v%), yeast extract (1 w / v%), lactose (3 w / v%) and milk protein (5 w / v%) in 2 L Kolben, Sterilized by heating at 121 ° C. for 15 minutes.
- This medium is inoculated with 1 v / v% of Bifidobacterium breve YIT 4065 strain (FERM BP-6223) and cultured anaerobically at 36 ° C. for about 20 hours while maintaining the pH at 5.5 with sodium hydroxide. To obtain a culture solution.
- This culture solution was centrifuged at 15,000 ⁇ G to collect Bifidobacterium bacteria.
- the composition of the mineral liquid is potassium (I) phosphate (10 w / v%), potassium (II) phosphate (20 w / v%), sodium acetate (30 w / v%) and ammonium sulfate (30 w / v%). ).
- 100 mL of a dispersion liquid in which 8 w / v% milk protein and 4 w / v% sugar were dispersed was prepared and sterilized by heating at 121 ° C. for 15 minutes.
- Test Example 3 Hairless mice Hos: HR-1 (6 weeks of age) were acclimated for 1 week after delivery, and then 5 mice were divided into a total of 3 groups. Among the mouse groups, physiological saline was orally administered to the first group and the second group, and the bacterial cell sample prepared in Example 3 was orally administered to the third group for 9 days at 0.1 mL / day. In addition, the first group is not irradiated with ultraviolet rays, and the second and third groups are subjected to ultraviolet irradiation apparatus (Toshiba SE-FL-20) together with the administration for 6 days from the sixth day after the start of administration.
- ultraviolet irradiation apparatus Toshiba SE-FL-20
- Ultraviolet rays containing 280 to 400 nm were irradiated at 40 mJ / cm 2 per day, and then the back skin was collected.
- physiological saline is administered and the mice that are not irradiated with ultraviolet rays are defined as blank groups
- physiological saline is administered
- the mice that are irradiated with ultraviolet rays are defined as control groups
- the bacterial cell sample is administered.
- a group of mice irradiated with ultraviolet rays was defined as a bacterial cell group (Table 3).
- UV + indicates that UV irradiation has been performed
- UV- indicates that UV irradiation has not been performed.
- Example 4 (Preparation of bacterial cell sample) 1.5 L of a medium prepared using mineral liquid (1 w / v%), yeast extract (1 w / v%), lactose (3 w / v%) and milk protein (5 w / v%) in 2 L Kolben, Sterilized by heating at 121 ° C. for 15 minutes.
- This medium is inoculated with 1 v / v% of Bifidobacterium breve YIT 12272 strain (FERM ABP-11320) and cultured anaerobically at 36 ° C. for about 20 hours while maintaining the pH at 5.5 with sodium hydroxide. To obtain a culture solution.
- This culture solution was centrifuged at 15,000 ⁇ G to collect Bifidobacterium bacteria.
- the composition of the mineral liquid is potassium (I) phosphate (10 w / v%), potassium (II) phosphate (20 w / v%), sodium acetate (30 w / v%) and ammonium sulfate (30 w / v%). ).
- 100 mL of a dispersion liquid in which 8 w / v% milk protein and 4 w / v% sugar were dispersed was prepared and sterilized by heating at 121 ° C. for 15 minutes.
- Test Example 4 Hairless mice Hos: HR-1 (6 weeks old) were acclimated for 1 week after delivery, and then 6 mice were divided into a total of 3 groups. Among the mouse groups, physiological saline was orally administered to the first group and the second group, and the bacterial cell sample prepared in Example 4 was orally administered to the third group for 9 days at 0.1 mL / day. In addition, UV irradiation was not performed for the first group, and for the second and third groups, the UV irradiation apparatus (Toshiba SE-FL-20) was used together with the administration for 6 days from the start of the administration for 4 days.
- Toshiba SE-FL-20 the UV irradiation apparatus
- Ultraviolet rays containing 280 to 400 nm were irradiated at 50 mJ / cm 2 per day, and then the back skin was collected.
- physiological saline is administered and the mice that are not irradiated with ultraviolet rays are defined as blank groups
- physiological saline is administered
- the mice that are irradiated with ultraviolet rays are defined as control groups
- the bacterial cell sample is administered.
- a group of mice irradiated with ultraviolet rays was defined as a bacterial cell group (Table 4).
- UV + indicates that UV irradiation is performed
- UV- indicates that UV irradiation is not performed.
- PBS phosphate buffered saline
- PBS phosphate buffered saline
- Polytron centrifuged at 14,000 ⁇ G
- 100 ⁇ L of the supernatant is dispensed into a 96-well plate, replacing elastin.
- 20 ⁇ L of succinyl-L-alanyl-L-alanyl-L-alanine-p-nitroanilide 6.25 mM as a synthetic substrate was added as an artificial substrate and incubated at 37 ° C. for 24 hours. Thereafter, the absorbance at 405 nm was measured.
- P-Nitroaniline was used as a standard to represent elastase activity in skin homogenate. The results are shown in FIG.
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Abstract
Description
したがって、生体はDNA損傷の種類に対応する種々の修復機構によって、普遍的にDNAの損傷を修復し、ゲノム情報及びその機能を維持している。この修復機構の代表例としては、DNAの二本鎖切断に対する相同的組み換え修復機構、活性酸素種による酸化的塩基損傷に対する塩基除去修復機構、紫外線によって生成するピリミジン二量体に対するヌクレオチド除去修復機構、複製エラーに対するミスマッチ修復機構などがある。
しかしながら、DNA損傷抑制とDNA損傷修復とは異なるものであり、上記のような発がん性物質に起因するDNA損傷抑制は、経口摂取した細菌を消化管の表面に吸着させることによって、或いは発がん性物質を細菌菌体へ吸着させ排出することによって、経口投与した種々の発がん性物質の生体への接触・吸収を抑えるものであることから、DNA損傷の修復を促進するものではないと考えられている。
これに対し、皮膚老化の防止・改善を目的とした種々のエラスターゼ活性阻害剤が提案されており、例えば、美容効果を目的とした、シソ葉の発酵物(特許文献2)、パセリの発酵物(特許文献3)又はピーマンの発酵物(特許文献4)を含有するエラスターゼ活性阻害剤が知られている。
しかしながら、上記発酵物のエラスターゼ活性阻害は、ヒト好中球由来エラスターゼや豚膵臓由来エラスターゼ溶液に被験物質を添加して行うin vitro試験により評価されたものであり、in vivo試験でエラスターゼ活性阻害が確認されたものではない。実際に皮膚に塗布した物質がエラスターゼ活性抑制作用を発揮するためには、有効成分が角層と表皮を透過して真皮層に到達する必要があるため、in vivoでの当該作用が確認されたエラスターゼ活性抑制剤が望まれていた。
本発明の課題は、経口用DNA損傷修復促進剤及び経口用エラスターゼ活性抑制剤を提供することにある。
ii)また、本発明は、ビフィドバクテリウム属細菌を有効成分として含有する経口用シクロブタンピリミジンダイマー量低下促進剤を提供するものである。
iii)更に、本発明は、ビフィドバクテリウム属細菌を有効成分として含有する経口用エラスターゼ活性抑制剤を提供するものである。
iv)更に、本発明は、皮膚老化防止・改善剤である、上記iii)に記載のエラスターゼ活性抑制剤を提供するものである。
vi)更に、本発明は、ビフィドバクテリウム属細菌を経口投与することを特徴とするシクロブタンピリミジンダイマー量低下促進方法を提供するものである。
vii)更に、本発明は、ビフィドバクテリウム属細菌を経口投与することを特徴とするエラスターゼ活性抑制方法を提供するものである。
viii)更に、本発明は、皮膚老化防止・改善方法である、上記vii)に記載の方法を提供するものである。
x)更に、本発明は、経口投与によりシクロブタンピリミジンダイマー量の低下を促進するために用いるビフィドバクテリウム属細菌を提供するものである。
xi)更に、本発明は、経口投与によりエラスターゼ活性を抑制するために用いるビフィドバクテリウム属細菌を提供するものである。
xii)更に、本発明は、皮膚老化を防止・改善するために用いるものである、上記xi)に記載の細菌を提供するものである。
xiv)更に、本発明は、経口用シクロブタンピリミジンダイマー量低下促進剤製造のためのビフィドバクテリウム属細菌の使用を提供するものである。
xv)更に、本発明は、経口用エラスターゼ活性抑制剤製造のためのビフィドバクテリウム属細菌の使用を提供するものである。
xvi)更に、本発明は、皮膚老化防止・改善剤製造のためのものである、上記xv)に記載の使用を提供するものである。
また、本発明によれば、経口投与することにより、エラスターゼの活性を抑制することができる。したがって、本発明の経口用エラスターゼ活性抑制剤は、皮膚の老化を防止・改善するための医薬品、飲食品等として有用である。
上記ビフィドバクテリウム属細菌としては、細菌菌体(生菌);加熱菌体(死菌体)、その凍結乾燥物、細菌の超音波等による破砕液、細菌の酵素処理液が好ましい。この中でも、DNA損傷修復促進作用及びエラスターゼ活性抑制作用の点から、細菌菌体(生菌)、上記の凍結乾燥物が特に好ましい。
なお、前記死菌体は、例えば、加熱処理、抗生物質等の薬物による処理、ホルマリン等の化学物質による処理、紫外線による処理、γ線等の放射線による処理により得ることができる。
本発明において、「DNA損傷修復促進」とは、損傷したDNA分子の修復を促進することを意味する。本発明のビフィドバクテリウム属細菌は、後記実施例に示すように、経口投与によりシクロブタンピリミジンダイマー(以下、CPDともいう)量の低下を促進するため、DNA損傷に対する優れた修復促進作用を有する。
したがって、ビフィドバクテリウム属細菌は、DNA損傷修復促進剤として使用することができ、また、DNA損傷修復促進剤を製造するために使用することができる。
そして、DNA損傷の修復を促進することによって、癌及び老化を予防・治療できることから、ビフィドバクテリウム属細菌は、癌又は老化の予防・治療剤ともなり得、上記DNA損傷修復促進剤は、癌や老化を予防・治療するための、ヒト又は動物用の医薬品、医薬部外品、飲食品、ペットフード等として有用である。
また、本発明のDNA損傷修復促進剤は、紫外線暴露によって生じたDNA損傷の修復を促進できることから、ビフィドバクテリウム属細菌は、皮膚癌又は皮膚老化の予防・治療剤ともなり得る。
本発明のCPD量低下促進剤は、DNA損傷の指標であるCPD量を低下させることから、ビフィドバクテリウム属細菌は、癌又は老化の予防・治療剤ともなり得、CPDは紫外線暴露によって生じるものであることから、本発明のCPD量低下促進剤は、特に皮膚癌又は皮膚老化の予防・治療剤として有用である。
本発明のビフィドバクテリウム属細菌は、後記実施例に示すように、経口投与することにより、紫外線暴露により亢進した皮膚中のエラスターゼの活性を抑制する作用を有する。したがって、ビフィドバクテリウム属細菌は、エラスターゼ活性抑制剤として使用することができ、また、エラスターゼ活性抑制剤を製造するために使用することができる。
そして、エラスターゼ活性を抑制することは、皮膚の老化を防止・改善することから、ビフィドバクテリウム属細菌は、皮膚老化防止・改善剤ともなり得、上記エラスターゼ活性抑制剤は、皮膚老化を防止・改善するための、ヒト又は動物用の医薬品、医薬部外品、飲食品、ペットフード等として有用である。なお、「皮膚老化防止・改善」とは、皮膚のシワ予防・改善、たるみ防止、弾力性改善、抗老化を含むものである。
DNA損傷修復促進剤、エラスターゼ活性抑制剤及び皮膚老化防止・改善剤の投与形態は、経口投与である。当該投与は、紫外線暴露前、紫外線暴露中、紫外線暴露後のいずれにおこなってもよい。中でも、DNA損傷修復促進作用、エラスターゼ活性抑制作用及び皮膚老化防止・改善作用の点から、少なくとも紫外線暴露前に投与するのが好ましく、紫外線暴露前及び紫外線暴露中に投与するのがより好ましい。また、紫外線暴露前から投与する場合、当該暴露前の投与期間は、DNA損傷修復促進作用、エラスターゼ活性抑制作用及び皮膚老化防止・改善作用の点から、5日間以上が好ましく、5~10日間がより好ましい。なお、10日間以上長期に投与しても、DNA損傷修復促進作用、エラスターゼ活性抑制作用及び皮膚老化防止・改善作用は期待できる。
上記滑沢剤としては、例えば、タルク、ロウ類、水素添加植物油、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸アルミニウム、ポリエチレングリコール等が挙げられる。
上記流動性促進剤としては、例えば、軽質無水ケイ酸、乾燥水酸化アルミニウムゲル、合成ケイ酸アルミニウム、ケイ酸マグネシウム等が挙げられる。
また、これら発酵飲食品の製造は常法にしたがって製造することができる。例えば発酵乳は、殺菌した乳培地にビフィドバクテリウム属細菌を接種培養し、これを均質化処理して発酵乳ベースを得る。次いで別途調製したシロップ溶液を添加混合し、ホモゲナイザー等で均質化し、さらにフレーバーを添加して最終製品とすることができる。このようにして得られる発酵乳は、プレーンタイプ、ソフトタイプ、フルーツフレーバータイプ、固形状、液状等のいずれの形態の製品とすることもできる。
本発明のDNA損傷修復促進剤、エラスターゼ活性抑制剤及び皮膚老化防止・改善剤の有効成分であるビフィドバクテリウム属細菌を使用する際の投与量に厳格な制限はない。対象者や適用疾患等の様々な使用態様によって得られる効果が異なるため、適宜投与量を設定することが望ましいが、DNA損傷修復促進作用、エラスターゼ活性抑制作用及び皮膚老化防止・改善作用の点から、ビフィドバクテリウム属細菌の菌数を、1×103CFU以上を1日量として含有する量が好ましく、1×103~1×1013CFUを1日量として含有する量がより好ましく、1×106~1×1010CFUを1日量として含有する量が特に好ましい。
Rogosaらの培地(Eftymiou C. et al., J infect dis., 110, 258-267, 1962)を改変した下記の組成の培地を121℃、15分間加熱殺菌した。この培地にビフィドバクテリウム・ブレーベYIT 4065株(FERM BP-6223)を1v/v%接種し、37℃でおよそ20時間嫌気的に培養して培養液を得た。この培養液を3500×Gで遠心分離し、ビフィドバクテリウム属細菌の菌体を集菌した。この菌体を1.0×1010CFU/mLになるように生理食塩水に懸濁させ、菌体溶液を得た。
Trypticase:1%、 Yeast extract:0.5%、 Tryptose:0.3%、 リン酸(I)カリウム:0.3%、 リン酸(II)カリウム:0.39%、 クエン酸アンモニウム:0.2%、 乳糖:1%、 L-システイン塩酸塩:0.03%、 Tween80:0.1%、 塩溶液0.5%(MgSO4・7H2O:11.5g、 FeSO4・7H2O:0.68g、 MnSO4・2H2O:2.4gを100mLの水に溶解したもの)
上記菌体溶液について、CPD量を測定することによりDNA修復促進効果を検討した。
ヘアレスマウスHos:HR-1(6週齢)を、搬入後1週間馴化させた後、6匹ずつ計8群に分け、それぞれ第1群~第8群とした。
上記マウス群のうち第1群、第3群、第5群及び第7群(以下、対照群ともいう)には生理食塩水を、第2群、第4群、第6群及び第8群(以下、菌体群ともいう)には実施例1で調製した菌体溶液を、それぞれ9日間0.1mL/day経口投与した。
また、上記第1群及び第2群については紫外線を照射せず、第3群~第8群については投与開始から6日目以降4日間、前記投与と共に紫外線照射装置(東芝SE-FL-20)により、280~400nmを含む紫外線を1日あたり40mJ/cm2照射した。
そして、第1群及び第2群については最後の投与から24時間後、第3群及び第4群については最後の照射から6時間後、第5群及び第6群については最後の照射から12時間後、第7群及び第8群については最後の照射から24時間後に、それぞれ背部皮膚を採取した。
なお、下記表1において、UV+は紫外線照射したこと、UV-は紫外線照射していないことを示す。
ミネラル液(1w/v%)、酵母エキス(1w/v%)、乳糖(3w/v%)及び乳蛋白質(5w/v%)を用いて調製した培地を2Lコルベンに1.5L作製し、121℃で15分間加熱殺菌した。この培地にビフィドバクテリウム・ブレーベYIT 12272株(FERM ABP-11320)を1v/v%接種し、水酸化ナトリウムでpHを5.5に保持しながら36℃でおよそ20時間嫌気的に培養して培養液を得た。この培養液を15,000×Gで遠心分離し、ビフィドバクテリウム属細菌の菌体を集菌した。なお、前記ミネラル液の組成は、リン酸(I)カリウム(10w/v%)、リン酸(II)カリウム(20w/v%)、酢酸ナトリウム(30w/v%)及び硫酸アンモニウム(30w/v%)である。
一方、乳蛋白質8w/v%及び糖質4w/v%を分散させた分散液を100mL調製し、121℃で15分間加熱殺菌した。この分散液に、上記集菌したビフィドバクテリウム属細菌の菌体を湿重量当り15%分散させ、その後凍結乾燥して、ビフィドバクテリウム・ブレーベYIT 12272株(FERM ABP-11320)の凍結乾燥菌体を得た。この凍結乾燥菌体を4×109CFU/mLとなるように生理食塩水10mLに懸濁し、菌体試料を得た。
ヘアレスマウスHos:HR-1(6週齢)を、搬入後1週間馴化させた後、3匹ずつ合計3群に分け、それぞれ第1群~第3群とした。
上記マウス群のうち、第1群及び第2群には生理食塩水を、第3群には実施例2で調製した菌体試料を、それぞれ9日間0.1mL/day経口投与した。
また、上記第1群については紫外線照射をせず、第2群及び第3群については、投与開始から6日目以降4日間、前記投与と共に紫外線照射装置(東芝SE-FL-20)により、280~400nmを含む紫外線を1日あたり50mJ/cm2照射し、その後、背部皮膚を採取した。
なお、上記マウス群のうち、生理食塩水を投与し、紫外線照射していないマウス群をblank群とし、生理食塩水を投与し、紫外線照射したマウス群を対照群とし、菌体試料を投与し、紫外線照射したマウス群を菌体群とした(表2)。下記表2において、UV+は紫外線照射したこと、UV-は紫外線照射していないことを示す。
ミネラル液(1w/v%)、酵母エキス(1w/v%)、乳糖(3w/v%)及び乳蛋白質(5w/v%)を用いて調製した培地を2Lコルベンに1.5L作製し、121℃で15分間加熱殺菌した。この培地にビフィドバクテリウム・ブレーベYIT 4065株(FERM BP-6223)を1v/v%接種し、水酸化ナトリウムでpHを5.5に保持しながら36℃でおよそ20時間嫌気的に培養して培養液を得た。この培養液を15,000×Gで遠心分離し、ビフィドバクテリウム属細菌の菌体を集菌した。なお、前記ミネラル液の組成は、リン酸(I)カリウム(10w/v%)、リン酸(II)カリウム(20w/v%)、酢酸ナトリウム(30w/v%)及び硫酸アンモニウム(30w/v%)である。
一方、乳蛋白質8w/v%及び糖質4w/v%を分散させた分散液を100mL調製し、121℃で15分間加熱殺菌した。この分散液に、上記集菌したビフィドバクテリウム属細菌の菌体を湿重量当り15%分散させ、その後凍結乾燥して、ビフィドバクテリウム・ブレーベYIT 4065株(FERM BP-6223)の凍結乾燥菌体を得た。この凍結乾燥菌体を1.0×1010CFU/mLとなるように生理食塩水10mLに懸濁し、菌体試料を得た。
ヘアレスマウスHos:HR-1(6週齢)を、搬入後1週間馴化させた後、5匹ずつ合計3群に分け、それぞれ第1群~第3群とした。
上記マウス群のうち、第1群及び第2群には生理食塩水を、第3群には実施例3で調製した菌体試料を、それぞれ9日間0.1mL/day経口投与した。
また、上記第1群については紫外線照射をせず、第2群及び第3群については、投与開始から6日目以降4日間、前記投与と共に紫外線照射装置(東芝SE-FL-20)により、280~400nmを含む紫外線を1日あたり40mJ/cm2照射し、その後、背部皮膚を採取した。
なお、上記マウス群のうち、生理食塩水を投与し、紫外線照射していないマウス群をblank群とし、生理食塩水を投与し、紫外線照射したマウス群を対照群とし、菌体試料を投与し、紫外線照射したマウス群を菌体群とした(表3)。下記表3において、UV+は紫外線照射したこと、UV-は紫外線照射していないことを示す。
ミネラル液(1w/v%)、酵母エキス(1w/v%)、乳糖(3w/v%)及び乳蛋白質(5w/v%)を用いて調製した培地を2Lコルベンに1.5L作製し、121℃で15分間加熱殺菌した。この培地にビフィドバクテリウム・ブレーベYIT 12272株(FERM ABP-11320)を1v/v%接種し、水酸化ナトリウムでpHを5.5に保持しながら36℃でおよそ20時間嫌気的に培養して培養液を得た。この培養液を15,000×Gで遠心分離し、ビフィドバクテリウム属細菌の菌体を集菌した。なお、前記ミネラル液の組成は、リン酸(I)カリウム(10w/v%)、リン酸(II)カリウム(20w/v%)、酢酸ナトリウム(30w/v%)及び硫酸アンモニウム(30w/v%)である。
一方、乳蛋白質8w/v%及び糖質4w/v%を分散させた分散液を100mL調製し、121℃で15分間加熱殺菌した。この分散液に、上記集菌したビフィドバクテリウム属細菌の菌体を湿重量当り15%分散させ、その後凍結乾燥して、ビフィドバクテリウム・ブレーベYIT 12272株(FERM ABP-11320)の凍結乾燥菌体を得た。この凍結乾燥菌体を4×109CFU/mLとなるように生理食塩水10mLに懸濁し、菌体試料を得た。
ヘアレスマウスHos:HR-1(6週齢)を、搬入後1週間馴化させた後、6匹ずつ合計3群に分け、それぞれ第1群~第3群とした。
上記マウス群のうち、第1群及び第2群には生理食塩水を、第3群には実施例4で調製した菌体試料を、それぞれ9日間0.1mL/day経口投与した。
また、上記第1群については紫外線照射をせず、第2群及び第3群については、投与開始から6日目以降4日間、前記投与と共に紫外線照射装置(東芝SE-FL-20)により、280~400nmを含む紫外線を1日あたり50mJ/cm2照射し、その後、背部皮膚を採取した。
なお、上記マウス群のうち、生理食塩水を投与し、紫外線照射していないマウス群をblank群とし、生理食塩水を投与し、紫外線照射したマウス群を対照群とし、菌体試料を投与し、紫外線照射したマウス群を菌体群とした(表4)。下記表4において、UV+は紫外線照射したこと、UV-は紫外線照射していないことを示す。
Claims (42)
- ビフィドバクテリウム属細菌を有効成分として含有する経口用DNA損傷修復促進剤。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項1に記載のDNA損傷修復促進剤。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項1又は2に記載のDNA損傷修復促進剤。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として含有する請求項1~3のいずれか1項に記載のDNA損傷修復促進剤。
- DNA損傷修復が、紫外線暴露によって引き起こされる皮膚中のDNA損傷に対する修復である請求項1~4のいずれか1項に記載のDNA損傷修復促進剤。
- 少なくとも紫外線暴露前に経口投与するものである請求項5に記載のDNA損傷修復促進剤。
- ビフィドバクテリウム属細菌を有効成分として含有する経口用シクロブタンピリミジンダイマー量低下促進剤。
- ビフィドバクテリウム属細菌を有効成分として含有する経口用エラスターゼ活性抑制剤。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項8に記載のエラスターゼ活性抑制剤。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項8又は9に記載のエラスターゼ活性抑制剤。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として含有する請求項8~10のいずれか1項に記載のエラスターゼ活性抑制剤。
- 紫外線暴露により亢進した皮膚中のエラスターゼ活性を抑制するものである請求項11に記載のエラスターゼ活性抑制剤。
- 少なくとも紫外線暴露前に経口投与するものである請求項12に記載のエラスターゼ活性抑制剤。
- 皮膚老化防止・改善剤である、請求項8~13のいずれか1項に記載のエラスターゼ活性抑制剤。
- ビフィドバクテリウム属細菌を経口投与することを特徴とするDNA損傷修復促進方法。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項15に記載の方法。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項15又は16に記載の方法。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として経口投与する請求項15~17のいずれか1項に記載の方法。
- DNA損傷修復が、紫外線暴露によって引き起こされる皮膚中のDNA損傷に対する修復である請求項15~18のいずれか1項に記載の方法。
- 少なくとも紫外線暴露前に経口投与するものである請求項19に記載の方法。
- ビフィドバクテリウム属細菌を経口投与することを特徴とするシクロブタンピリミジンダイマー量低下促進方法。
- ビフィドバクテリウム属細菌を経口投与することを特徴とするエラスターゼ活性抑制方法。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項22に記載の方法。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項22又は23に記載の方法。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として経口投与する請求項22~24のいずれか1項に記載の方法。
- 紫外線暴露により亢進した皮膚中のエラスターゼ活性を抑制するものである請求項22~25のいずれか1項に記載の方法。
- 少なくとも紫外線暴露前に経口投与するものである請求項26に記載の方法。
- 皮膚老化防止・改善方法である請求項22~27のいずれか1項に記載の方法。
- 経口投与によりDNAの損傷の修復を促進するために用いるビフィドバクテリウム属細菌。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項29に記載の細菌。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項29又は30に記載の細菌。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として経口投与するためのものである請求項29~31のいずれか1項に記載の細菌。
- DNA損傷修復が、紫外線暴露によって引き起こされる皮膚中のDNA損傷に対する修復である請求項29~32のいずれか1項に記載の細菌。
- 少なくとも紫外線暴露前に経口投与するためのものである請求項33に記載の細菌。
- 経口投与によりシクロブタンピリミジンダイマー量の低下を促進するために用いるビフィドバクテリウム属細菌。
- 経口投与によりエラスターゼ活性を抑制するために用いるビフィドバクテリウム属細菌。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベである請求項36に記載の細菌。
- ビフィドバクテリウム属細菌が、ビフィドバクテリウム・ブレーベ YIT 4065又はビフィドバクテリウム・ブレーベYIT 12272である請求項36又は37に記載の細菌。
- ビフィドバクテリウム属細菌を、1×103CFU以上を1日量として経口投与するためのものである請求項36~38のいずれか1項に記載の細菌。
- 紫外線暴露により亢進した皮膚中のエラスターゼ活性を抑制するものである請求項39に記載の細菌。
- 少なくとも紫外線暴露前に経口投与するためのものである請求項36~40のいずれか1項に記載の細菌。
- 皮膚老化を防止・改善するために用いるものである、請求項36~41のいずれか1項に記載の細菌。
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US13/520,912 US20130004463A1 (en) | 2010-01-06 | 2010-12-28 | Dna damage repair promoter for oral application, and elastase activity inhibitor for oral application |
EP10842249.4A EP2522355B1 (en) | 2010-01-06 | 2010-12-28 | Dna damage repair promoter for oral application, and elastase activity inhibitor for oral application |
BR112012016676-0A BR112012016676A2 (ja) | 2010-01-06 | 2010-12-28 | The DNA damage restoration catalyst and elastase active depressant for taking orally |
JP2011548976A JP5688376B2 (ja) | 2010-01-06 | 2010-12-28 | 経口用のdna損傷修復促進剤及びエラスターゼ活性抑制剤 |
MX2012007873A MX2012007873A (es) | 2010-01-06 | 2010-12-28 | Promotor de reparacion del daño de acido desoxirribonucleico para aplicacion oral e inhibidor de la actividad de elastasa para apalicacion oral. |
KR1020127017366A KR101807328B1 (ko) | 2010-01-06 | 2010-12-28 | 경구용 dna 손상 수복 촉진제 및 엘라스타아제 활성 억제제 |
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BR (1) | BR112012016676A2 (ja) |
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WO2015083743A1 (ja) | 2013-12-04 | 2015-06-11 | 株式会社ヤクルト本社 | 微生物の酸耐性調節方法 |
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WO2022064839A1 (ja) * | 2020-09-24 | 2022-03-31 | 森永乳業株式会社 | コラーゲン、エラスチン若しくはヒアルロン酸の産生又は分解に関与する遺伝子の発現調節用組成物 |
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WO2015066382A1 (en) * | 2013-10-30 | 2015-05-07 | ChromaDex Inc. | Nicotinamide riboside compositions for topical use in treating skin conditions |
BR112018007560A2 (pt) * | 2015-10-15 | 2018-10-23 | Natura Cosméticos S.A. | composição cosmética tendo bactérias probióticas |
WO2020067170A1 (ja) * | 2018-09-25 | 2020-04-02 | 国立研究開発法人国立循環器病研究センター | 抗腫瘍効果増強剤 |
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JPWO2014142186A1 (ja) * | 2013-03-13 | 2017-02-16 | 株式会社ヤクルト本社 | ビフィドバクテリウム・ブレーベ株特異的遺伝子 |
WO2015083743A1 (ja) | 2013-12-04 | 2015-06-11 | 株式会社ヤクルト本社 | 微生物の酸耐性調節方法 |
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Also Published As
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BR112012016676A2 (ja) | 2018-06-05 |
US20130004463A1 (en) | 2013-01-03 |
KR101807328B1 (ko) | 2017-12-08 |
EP2522355A1 (en) | 2012-11-14 |
TWI565471B (zh) | 2017-01-11 |
MX2012007873A (es) | 2012-07-25 |
KR20120112510A (ko) | 2012-10-11 |
EP2522355B1 (en) | 2018-02-21 |
EP2522355A4 (en) | 2014-06-04 |
TW201130496A (en) | 2011-09-16 |
JP5688376B2 (ja) | 2015-03-25 |
JPWO2011083738A1 (ja) | 2013-05-13 |
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