WO2013018706A1 - Composition for regulating urat1 activity - Google Patents
Composition for regulating urat1 activity Download PDFInfo
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- WO2013018706A1 WO2013018706A1 PCT/JP2012/069167 JP2012069167W WO2013018706A1 WO 2013018706 A1 WO2013018706 A1 WO 2013018706A1 JP 2012069167 W JP2012069167 W JP 2012069167W WO 2013018706 A1 WO2013018706 A1 WO 2013018706A1
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- Prior art keywords
- composition
- urat1
- present
- regulating
- activity
- Prior art date
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- 230000000694 effects Effects 0.000 title claims abstract description 25
- 239000000203 mixture Substances 0.000 title claims abstract description 21
- 230000001105 regulatory effect Effects 0.000 title claims abstract description 10
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229960003080 taurine Drugs 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
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- 101000821903 Homo sapiens Solute carrier family 22 member 12 Proteins 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
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- 239000003814 drug Substances 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 7
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- 229940079593 drug Drugs 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 239000008187 granular material Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
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- 238000000034 method Methods 0.000 description 4
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- 235000013376 functional food Nutrition 0.000 description 3
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- 239000003826 tablet Substances 0.000 description 3
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- 235000015429 Mirabilis expansa Nutrition 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
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- 239000002552 dosage form Substances 0.000 description 2
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- 239000004503 fine granule Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
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- 235000013536 miso Nutrition 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
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- 241001465754 Metazoa Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108091006745 SLC22A12 Proteins 0.000 description 1
- 102100030935 Solute carrier family 2, facilitated glucose transporter member 9 Human genes 0.000 description 1
- 101710102931 Solute carrier family 22 member 12 Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
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- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 description 1
- 229960002529 benzbromarone Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 235000015071 dressings Nutrition 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 235000019985 fermented beverage Nutrition 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000021110 pickles Nutrition 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 108010078530 urate transporter Proteins 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
Definitions
- the present invention relates to a composition for regulating URAT1 activity.
- the kidney is involved in the excretion of various substances such as in vivo factors, drugs, nutrients, functional factors, and compounds, and the excretion is regulated by transporters expressed in the kidney.
- URAT1 urate transporter 1 expressed in the kidney is known to be involved in the transport of uric acid, nicotinic acid, succinic acid, and other factors that play important roles in the body, as well as drugs such as salicylic acid and indomethacin. It has been suggested that the biological function can be adjusted well by adjusting the activity (see Non-Patent Document 1).
- benzbromarone known as a URAT1 activity regulator is used as a drug for improving hyperuricemia.
- URAT1 activity regulators are still being searched for (see Non-Patent Document 2), no URAT1 activity regulator that is safe even if taken daily has not been known so far.
- Taurine (aminoethyl sulfonic acid) is a kind of sulfur-containing amino acid, and it can be said to be a highly safe component because it is taken daily as a pharmaceutical, quasi-drug or supplement throughout the world. Although various physiological actions are known for taurine (see Non-Patent Document 3), it is not known to regulate URAT1 activity.
- An object of the present invention is to provide a composition for regulating URAT1 activity that is safe even if taken daily.
- Such an embodiment of the present invention is a composition for regulating URAT1 activity characterized by containing taurine as an active ingredient.
- composition which is an orally administered agent.
- the present invention provides a composition for regulating URAT1 activity, comprising taurine as an active ingredient.
- URAT1 in the present invention is a transporter expressed in the kidney, and includes transporters with aliases such as RST, OAT4L, SLC22A12, and the like.
- a typical base sequence and amino acid sequence of URAT1 derived from human is disclosed in GenBank (AB071863).
- “regulates URAT1 activity” typically means that URAT1 activity is suppressed by decreasing the expression of the URAT1 gene.
- composition of the present invention may be in the form of a pharmaceutical composition (pharmaceuticals, quasi-drugs, etc.), food or drink, or a reagent used for research purposes (eg, in vivo experimental purposes).
- composition of the present invention When the composition of the present invention is used as a pharmaceutical composition, its dosage form is not particularly limited as long as it contains taurine as an active ingredient.
- the pharmaceutical composition of the present invention can be formulated into various dosage forms by known pharmaceutical methods. For example, tablet, granule, powder, capsule, pill, fine granule, fine granule, chewable, troche, film coating, pellet, sublingual, chewing agent, buccal, liquid, syrup, suspension It can be used orally or parenterally as a suspension, elixir, emulsion, paste, aerosol, injection, suppository and the like.
- the pharmaceutical composition of the present invention is preferably an oral administration agent.
- oral administration agent include solid preparations such as tablets, granules, powders, capsules, pills, fine granules, fine granules, chewable preparations, and lozenges, and oral liquid preparations such as drinks.
- compositions of the present invention When providing the pharmaceutical composition of the present invention as an orally administered agent, other active ingredients and known additives can be blended within a qualitative and quantitative range that does not impair the effects of the present invention.
- active ingredients and known additives can be blended within a qualitative and quantitative range that does not impair the effects of the present invention.
- composition of the present invention When the composition of the present invention is used as a pharmaceutical composition, one or more other components effective for regulating URAT1 activity can be blended. Moreover, you may use together with the other pharmaceutical composition effective in the regulation of URAT1 activity.
- the food or drink can be, for example, a health food, a functional food, a food for specified health use, a nutritional supplement, a food for a sick person, or a food additive.
- food and drink include liquid foods such as drinks, soups, milk beverages, soft drinks, tea beverages, alcoholic beverages, jelly-like beverages, functional beverages; oils such as edible oils, dressings, mayonnaise, margarines Products containing carbohydrates; Foods containing carbohydrates such as rice, noodles and bread; Livestock processed foods such as ham and sausage; Fish processed foods such as kamaboko, dried fish and salted; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectionery such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Examples include instant foods such as instant miso soup and foods for microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.
- the production of food and drink in the present invention can be performed by a production technique known in the technical field.
- the dose or intake of taurine as an active ingredient of the composition of the present invention is usually 100 to 3000 mg of taurine 1 to 3 times a day, preferably 1000 to 3000 mg 2 to 3 times a day in adults. Preferably, 1000 to 2000 mg at a time is 2 to 3 times a day, and this can be appropriately increased or decreased depending on the route of administration, age, sex, severity of symptoms, and the like.
- the present invention thus also provides a method of modulating URAT1 activity in a subject, characterized by administering or ingesting the composition of the present invention to the subject.
- the product of the composition of the present invention may be labeled with an indication that it is used to regulate URAT1 activity.
- labeled product or instructions means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to.
- the indication that it is used to modulate URAT1 activity can include information about the mechanism by which URAT1 activity is modulated by administering or ingesting the composition of the present invention.
- Table 1 shows the average value and standard error of the URAT1 mRNA amount in the control group and the taurine administration group, where the average value of the URAT1 mRNA amount in the control group is 100. As a result, the amount of URAT1 mRNA was significantly decreased in the taurine administration group compared with the control group (p ⁇ 0.05).
- the present invention is intended to be used for specific health purposes in eating habits, with the approval of Article 26, Paragraph 1 of Article 26, Paragraph 1 of the Health Promotion Act. It is possible to provide functional foods and the like that are permitted to display specific functions such as foods that indicate that the purpose of the health can be expected by ingestion.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The present invention provides a composition for regulating a URAT1 activity, characterized by containing taurine, which is a substance that is safe even when ingested on daily basis, as an active ingredient.
Description
本発明は、URAT1活性を調節するための組成物に関するものである。
The present invention relates to a composition for regulating URAT1 activity.
腎臓は生体内因子や薬物、栄養素、機能性因子、化合物等、様々な物質の排泄に関与しており、その排泄量は腎臓に発現するトランスポーターにより調節されている。腎臓に発現しているURAT1(urate transporter 1)は尿酸、ニコチン酸、コハク酸等、生体内で重要な役割を果たしている因子、さらにはサリチル酸やインドメタシンといった薬物の輸送に関与していることが知られており、その活性を調節することにより生体機能を良好に調節できる可能性が示唆されている(非特許文献1参照)。例えば、URAT1活性調節剤として知られているベンズブロマロンは、高尿酸血症改善医薬品として使用されている。また、URAT1活性調節剤が現在も探索されている(非特許文献2参照)が、日常的に摂取しても安全なURAT1活性調節剤は、これまでに知られていない。
The kidney is involved in the excretion of various substances such as in vivo factors, drugs, nutrients, functional factors, and compounds, and the excretion is regulated by transporters expressed in the kidney. URAT1 (urate transporter 1) expressed in the kidney is known to be involved in the transport of uric acid, nicotinic acid, succinic acid, and other factors that play important roles in the body, as well as drugs such as salicylic acid and indomethacin. It has been suggested that the biological function can be adjusted well by adjusting the activity (see Non-Patent Document 1). For example, benzbromarone known as a URAT1 activity regulator is used as a drug for improving hyperuricemia. Moreover, although URAT1 activity regulators are still being searched for (see Non-Patent Document 2), no URAT1 activity regulator that is safe even if taken daily has not been known so far.
タウリン(アミノエチルスルホン酸)は含硫アミノ酸の一種で、世界中で医薬品、医薬部外品あるいはサプリメント等として日常的に摂取されていることからも、安全性の高い成分であると言える。タウリンには様々な生理作用が知られているが(非特許文献3参照)、URAT1活性を調節することは知られていない。
Taurine (aminoethyl sulfonic acid) is a kind of sulfur-containing amino acid, and it can be said to be a highly safe component because it is taken daily as a pharmaceutical, quasi-drug or supplement throughout the world. Although various physiological actions are known for taurine (see Non-Patent Document 3), it is not known to regulate URAT1 activity.
本発明の目的は、日常的に摂取しても安全なURAT1活性を調節するための組成物を提供することである。
An object of the present invention is to provide a composition for regulating URAT1 activity that is safe even if taken daily.
本発明者らは、前記課題を解決すべく鋭意検討を重ねた結果、タウリンがURAT1活性を調節することを見出し、本発明を完成した。
As a result of intensive studies to solve the above problems, the present inventors have found that taurine regulates URAT1 activity and completed the present invention.
かかる本発明の態様は、タウリンを有効成分として含有することを特徴とするURAT1活性を調節するための組成物である。
Such an embodiment of the present invention is a composition for regulating URAT1 activity characterized by containing taurine as an active ingredient.
本発明の他の態様は、経口投与剤である前記組成物である。
Another aspect of the present invention is the above composition which is an orally administered agent.
本発明により、日常的に摂取しても安全な、URAT1活性を調節するための組成物を提供することが可能となった。
According to the present invention, it is possible to provide a composition for regulating URAT1 activity that is safe even if taken daily.
本発明は、タウリンを有効成分として含有することを特徴とするURAT1活性を調節するための組成物を提供する。
The present invention provides a composition for regulating URAT1 activity, comprising taurine as an active ingredient.
本発明における「URAT1」は、腎臓に発現するトランスポーターであり、RST、OAT4L、SLC22A12等の別名がつけられているトランスポーターをも包含する。ヒト由来のURAT1の典型的な塩基配列及びアミノ酸配列は、GenBank(AB071863)に開示されている。
“URAT1” in the present invention is a transporter expressed in the kidney, and includes transporters with aliases such as RST, OAT4L, SLC22A12, and the like. A typical base sequence and amino acid sequence of URAT1 derived from human is disclosed in GenBank (AB071863).
本発明において「URAT1活性を調節する」とは、典型的には、URAT1遺伝子の発現を低下させることにより、URAT1活性が発揮されるのを抑制することを意味する。
In the present invention, “regulates URAT1 activity” typically means that URAT1 activity is suppressed by decreasing the expression of the URAT1 gene.
本発明の組成物は、医薬組成物(医薬品、医薬部外品など)、飲食品、あるいは研究目的(例えば、インビボの実験目的など)に用いられる試薬の形態であり得る。
The composition of the present invention may be in the form of a pharmaceutical composition (pharmaceuticals, quasi-drugs, etc.), food or drink, or a reagent used for research purposes (eg, in vivo experimental purposes).
本発明の組成物を医薬組成物として用いる場合、有効成分としてタウリンを含有するものであればその剤形は特に限定されない。本発明の医薬組成物は、公知の製剤学的方法により種々の剤形で製剤化することができる。例えば、錠剤、顆粒剤、散剤、カプセル剤、丸剤、細粒剤、微粒剤、チュアブル剤、トローチ剤、フィルムコーティング剤、ペレット剤、舌下剤、咀嚼剤、バッカル剤、液剤、シロップ剤、懸濁剤、エリキシル剤、乳剤、ペースト剤、エアゾール剤、注射剤、坐剤などとして、経口的または非経口的に使用することができる。
When the composition of the present invention is used as a pharmaceutical composition, its dosage form is not particularly limited as long as it contains taurine as an active ingredient. The pharmaceutical composition of the present invention can be formulated into various dosage forms by known pharmaceutical methods. For example, tablet, granule, powder, capsule, pill, fine granule, fine granule, chewable, troche, film coating, pellet, sublingual, chewing agent, buccal, liquid, syrup, suspension It can be used orally or parenterally as a suspension, elixir, emulsion, paste, aerosol, injection, suppository and the like.
本発明の医薬組成物は、好ましくは、経口投与剤である。経口投与剤としては、錠剤、顆粒剤、散剤、カプセル剤、丸剤、細粒剤、微粒剤、チュアブル剤、トローチ剤などの内服固形製剤やドリンク剤などの内服液剤が挙げられる。
The pharmaceutical composition of the present invention is preferably an oral administration agent. Examples of the oral administration agent include solid preparations such as tablets, granules, powders, capsules, pills, fine granules, fine granules, chewable preparations, and lozenges, and oral liquid preparations such as drinks.
本発明の医薬組成物を経口投与剤として提供するに際しては、本発明の効果を損なわない質的及び量的範囲で、他の有効成分や公知の添加剤を配合することができる。このようなものとしては、生薬、天然物、賦形剤、pH調整剤、清涼化剤、懸濁化剤、粘稠剤、溶解補助剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味剤、界面活性剤、可塑剤、香料が挙げられる。
When providing the pharmaceutical composition of the present invention as an orally administered agent, other active ingredients and known additives can be blended within a qualitative and quantitative range that does not impair the effects of the present invention. Such as herbal medicines, natural products, excipients, pH adjusting agents, cooling agents, suspending agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants , Coating agents, colorants, flavoring agents, surfactants, plasticizers, and fragrances.
本発明の組成物を医薬組成物として用いる場合には、URAT1活性の調節に有効な1種もしくは2種以上の他の成分を配合することができる。また、URAT1活性の調節に有効な他の医薬組成物と併用してもよい。
When the composition of the present invention is used as a pharmaceutical composition, one or more other components effective for regulating URAT1 activity can be blended. Moreover, you may use together with the other pharmaceutical composition effective in the regulation of URAT1 activity.
本発明の組成物を飲食品として用いる場合、当該飲食品は、例えば、健康食品、機能性食品、特定保健用食品、栄養補助食品、病者用食品、あるいは食品添加物、であり得る。飲食品の具体例としては、ドリンク類、スープ類、乳飲料、清涼飲料水、茶飲料、アルコール飲料、ゼリー状飲料、機能性飲料等の液状食品;食用油、ドレッシング、マヨネーズ、マーガリンなどの油分を含む製品;飯類、麺類、パン類等の炭水化物含有食品;ハム、ソーセージ等の畜産加工食品;かまぼこ、干物、塩辛等の水産加工食品;漬物等の野菜加工食品;ゼリー、ヨーグルト等の半固形状食品;みそ、発酵飲料等の発酵食品;洋菓子類、和菓子類、キャンディー類、ガム類、グミ、冷菓、氷菓等の各種菓子類;カレー、あんかけ、中華スープ等のレトルト製品;インスタントスープ,インスタントみそ汁等のインスタント食品や電子レンジ対応食品等が挙げられる。さらには、粉末、穎粒、錠剤、カプセル剤、液状、ペースト状またはゼリー状に調製された健康飲食品も挙げられる。
When the composition of the present invention is used as a food or drink, the food or drink can be, for example, a health food, a functional food, a food for specified health use, a nutritional supplement, a food for a sick person, or a food additive. Specific examples of food and drink include liquid foods such as drinks, soups, milk beverages, soft drinks, tea beverages, alcoholic beverages, jelly-like beverages, functional beverages; oils such as edible oils, dressings, mayonnaise, margarines Products containing carbohydrates; Foods containing carbohydrates such as rice, noodles and bread; Livestock processed foods such as ham and sausage; Fish processed foods such as kamaboko, dried fish and salted; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectionery such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Examples include instant foods such as instant miso soup and foods for microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.
本発明における飲食品の製造は、当該技術分野に公知の製造技術により実施することができる。当該飲食品においては、URAT1活性の調節に有効な1種もしくは2種以上の成分を配合してもよい。また、URAT1活性の調節以外の機能を発揮する他の成分あるいは他の機能性食品と組み合わせることによって、多機能性の飲食品としてもよい。
The production of food and drink in the present invention can be performed by a production technique known in the technical field. In the said food-drinks, you may mix | blend the 1 type, or 2 or more types of component effective in the regulation of URAT1 activity. Moreover, it is good also as multifunctional food-drinks by combining with the other component which exhibits functions other than control of URAT1 activity, or another functional food.
本発明の組成物の有効成分としてのタウリンの投与量または摂取量は、通常、成人ではタウリンとして100~3000mgを1日1~3回、好ましくは1000~3000mgを1日2~3回、さらに好ましくは1回1000~2000mgを1日2~3回であり、これは、投与ルート、年齢、性別、症状の重症度などにより適宜増減することも可能である。本発明は、このように、本発明の組成物を対象に投与もしくは摂取させることを特徴とする、対象におけるURAT1活性を調節する方法をも提供するものである。
The dose or intake of taurine as an active ingredient of the composition of the present invention is usually 100 to 3000 mg of taurine 1 to 3 times a day, preferably 1000 to 3000 mg 2 to 3 times a day in adults. Preferably, 1000 to 2000 mg at a time is 2 to 3 times a day, and this can be appropriately increased or decreased depending on the route of administration, age, sex, severity of symptoms, and the like. The present invention thus also provides a method of modulating URAT1 activity in a subject, characterized by administering or ingesting the composition of the present invention to the subject.
本発明の組成物の製品(医薬品、医薬部外品、飲食品、試薬など)またはその説明書は、URAT1活性の調節のために用いられる旨の表示を付したものであり得る。ここで「製品または説明書に表示を付した」とは、製品の本体、容器、包装などに表示を付したこと、あるいは製品の情報を開示する説明書、添付文書、宣伝物、その他の印刷物などに表示を付したことを意味する。URAT1活性の調節のために用いられる旨の表示においては、本発明の組成物を投与もしくは摂取することによりURAT1活性が調節される機序についての情報を含むことができる。
The product of the composition of the present invention (pharmaceuticals, quasi-drugs, foods and drinks, reagents, etc.) or instructions thereof may be labeled with an indication that it is used to regulate URAT1 activity. Here, “labeled product or instructions” means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to. The indication that it is used to modulate URAT1 activity can include information about the mechanism by which URAT1 activity is modulated by administering or ingesting the composition of the present invention.
以下に試験例により、本発明をさらに具体的に説明する。
Hereinafter, the present invention will be described in more detail with reference to test examples.
[試験例1]
5週齢の雌性Wistar Hannover/Rccラット(日本エスエルシー株式会社)を、各群の平均体重がほぼ同等となるように1群4匹で2群に分けた。 [Test Example 1]
Five-week-old female Wistar Hanover / Rcc rats (Japan SLC Co., Ltd.) were divided into two groups with four animals per group so that the average body weight of each group was approximately the same.
5週齢の雌性Wistar Hannover/Rccラット(日本エスエルシー株式会社)を、各群の平均体重がほぼ同等となるように1群4匹で2群に分けた。 [Test Example 1]
Five-week-old female Wistar Hanover / Rcc rats (Japan SLC Co., Ltd.) were divided into two groups with four animals per group so that the average body weight of each group was approximately the same.
対照群には水を、タウリン投与群にはタウリンを100mg/kgの用量で経口投与した。その24時間後にペントバルビタール麻酔下で開腹し、腎臓を摘出した。RNeasy Mini Kit(Qiagen社製)を用いてTotal RNAを抽出した。High Capacity RNA-to-cDNA Master Mix(Applied Biosystems社製)を用いて逆転写し、URAT1プライマー(Applied Biosystems社製)を用いて、Real Time PCR法にて腎臓中URAT1 mRNA量を測定した。
In the control group, water was orally administered to the taurine administration group in a dose of 100 mg / kg. 24 hours later, the abdomen was opened under pentobarbital anesthesia, and the kidney was removed. Total RNA was extracted using RNeasy Mini Kit (Qiagen). Reverse transcription was performed using High Capacity RNA-to-cDNA Master Mix (Applied Biosystems), and the amount of URAT1 mRNA in the kidney was measured by Real Time PCR method using URAT1 primer (Applied Biosystems).
対照群のURAT1 mRNA量の平均値を100としたときの、対照群およびタウリン投与群のURAT1 mRNA量の平均値および標準誤差を表1に示した。その結果、対照群と比較してタウリン投与群でURAT1 mRNA量が有意に低下した(p<0.05)。
Table 1 shows the average value and standard error of the URAT1 mRNA amount in the control group and the taurine administration group, where the average value of the URAT1 mRNA amount in the control group is 100. As a result, the amount of URAT1 mRNA was significantly decreased in the taurine administration group compared with the control group (p <0.05).
本発明は、医薬品、医薬部外品、あるいは特定保健用食品(健康増進法第26条第1項の許可又は第29条第1項の承認を受け、食生活において特定の保健の目的で摂取する者に対し、その摂取により当該保健の目的が期待できる旨の表示をする食品)等の特定の機能の表示が許可されている機能性食品等として提供することが可能である。
The present invention is intended to be used for specific health purposes in eating habits, with the approval of Article 26, Paragraph 1 of Article 26, Paragraph 1 of the Health Promotion Act. It is possible to provide functional foods and the like that are permitted to display specific functions such as foods that indicate that the purpose of the health can be expected by ingestion.
Claims (2)
- タウリンを有効成分として含有することを特徴とするURAT1活性を調節するための組成物。 A composition for regulating URAT1 activity, comprising taurine as an active ingredient.
- 経口投与剤である請求項1に記載の組成物。 The composition according to claim 1, which is an orally administered agent.
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Non-Patent Citations (6)
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HIDEO SATSU: "Taurin no Tasai na Seiri Sayo to Kino", KAGAKU TO SEIBUTSU, vol. 45, no. 4, 2007, pages 273 - 281 * |
ICHIRO HISATOME: "Impact of serum uric acid level on the cardiovascular system as a risk factor", FOLIA PHARMACOLOGICA JAPONICA, vol. 136, no. 6, 2010, pages 325 - 329 * |
SCHULLER-LEVIS, G. B. ET AL.: "Taurine: new implications for an old amino acid", FEMS MICROBIOLOGY LETTERS, vol. 226, no. 2, 2003, pages 195 - 202 * |
TATSUO HOSOYA: "Mechanism of Urate Excretion by the Kidney", JIKEIKAI MEDICAL JOURNAL, vol. 121, no. 2, 2006, pages 49 - 54 * |
WEMPE, M. F. ET AL.: "Developing Potent Human Uric Acid Transportation 1 (hURATI) Inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, no. 8, 30 March 2011 (2011-03-30), pages 2701 - 2713 * |
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