JP6654824B2 - Blood uric acid level reducer - Google Patents
Blood uric acid level reducer Download PDFInfo
- Publication number
- JP6654824B2 JP6654824B2 JP2015153508A JP2015153508A JP6654824B2 JP 6654824 B2 JP6654824 B2 JP 6654824B2 JP 2015153508 A JP2015153508 A JP 2015153508A JP 2015153508 A JP2015153508 A JP 2015153508A JP 6654824 B2 JP6654824 B2 JP 6654824B2
- Authority
- JP
- Japan
- Prior art keywords
- strain
- bifidobacterium
- uric acid
- purine
- acid level
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 title claims description 34
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 title claims description 34
- 229940116269 uric acid Drugs 0.000 title claims description 34
- 210000004369 blood Anatomy 0.000 title claims description 24
- 239000008280 blood Substances 0.000 title claims description 24
- 239000003638 chemical reducing agent Substances 0.000 title claims description 7
- 240000002605 Lactobacillus helveticus Species 0.000 claims description 34
- 235000013967 Lactobacillus helveticus Nutrition 0.000 claims description 34
- 229940054346 lactobacillus helveticus Drugs 0.000 claims description 34
- 241000186148 Bifidobacterium pseudolongum Species 0.000 claims description 31
- 241000894006 Bacteria Species 0.000 claims description 25
- 241001134770 Bifidobacterium animalis Species 0.000 claims description 13
- 229940118852 bifidobacterium animalis Drugs 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 9
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 claims description 8
- 229940004120 bifidobacterium infantis Drugs 0.000 claims description 8
- 235000013305 food Nutrition 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 235000016709 nutrition Nutrition 0.000 claims description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 39
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 36
- 239000002212 purine nucleoside Substances 0.000 description 30
- 235000014655 lactic acid Nutrition 0.000 description 18
- 239000004310 lactic acid Substances 0.000 description 18
- 150000003212 purines Chemical class 0.000 description 16
- 201000001431 Hyperuricemia Diseases 0.000 description 15
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 14
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 239000002609 medium Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 235000020183 skimmed milk Nutrition 0.000 description 11
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 10
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 10
- 241000186000 Bifidobacterium Species 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 description 9
- 239000002213 purine nucleotide Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 7
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 7
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 7
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 7
- 229930010555 Inosine Natural products 0.000 description 7
- 229960005305 adenosine Drugs 0.000 description 7
- 229940029575 guanosine Drugs 0.000 description 7
- 229960003786 inosine Drugs 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 5
- 241000186606 Lactobacillus gasseri Species 0.000 description 5
- 239000012620 biological material Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 235000013618 yogurt Nutrition 0.000 description 5
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229960000643 adenine Drugs 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 235000015140 cultured milk Nutrition 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 241001608472 Bifidobacterium longum Species 0.000 description 2
- 108010093894 Xanthine oxidase Proteins 0.000 description 2
- 102100033220 Xanthine oxidase Human genes 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 229940009291 bifidobacterium longum Drugs 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 101000821903 Homo sapiens Solute carrier family 22 member 12 Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100021495 Solute carrier family 22 member 12 Human genes 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 230000004144 purine metabolism Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000020185 raw untreated milk Nutrition 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B19/00—Programme-control systems
- G05B19/02—Programme-control systems electric
- G05B19/18—Numerical control [NC], i.e. automatically operating machines, in particular machine tools, e.g. in a manufacturing environment, so as to execute positioning, movement or co-ordinated operations by means of programme data in numerical form
- G05B19/416—Numerical control [NC], i.e. automatically operating machines, in particular machine tools, e.g. in a manufacturing environment, so as to execute positioning, movement or co-ordinated operations by means of programme data in numerical form characterised by control of velocity, acceleration or deceleration
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B15/00—Systems controlled by a computer
- G05B15/02—Systems controlled by a computer electric
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B2219/00—Program-control systems
- G05B2219/30—Nc systems
- G05B2219/42—Servomotor, servo controller kind till VSS
- G05B2219/42191—Adjust proportionality factor to optimize slave axis movement
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B2219/00—Program-control systems
- G05B2219/30—Nc systems
- G05B2219/43—Speed, acceleration, deceleration control ADC
- G05B2219/43048—Step change in reference, soft start, smoothing reference
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B2219/00—Program-control systems
- G05B2219/30—Nc systems
- G05B2219/50—Machine tool, machine tool null till machine tool work handling
- G05B2219/50234—Synchronize two spindles, axis, electronic transmission, line shafting
Landscapes
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Automation & Control Theory (AREA)
- General Engineering & Computer Science (AREA)
- Human Computer Interaction (AREA)
- Manufacturing & Machinery (AREA)
- Dairy Products (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
本発明は、血中尿酸値低減作用を有する乳酸菌およびその利用方法、ならびに、乳酸菌を含む高尿酸血症の予防および／または治療用の食品または医薬品に関する。 TECHNICAL FIELD The present invention relates to a lactic acid bacterium having a blood uric acid level-reducing action and a method for using the same, and a food or pharmaceutical product containing lactic acid bacterium for preventing and / or treating hyperuricemia.
血中に存在する尿酸の血中濃度が異常に高い状態（男女共に７．０ｍｇ／ｄＬ以上）を高尿酸血症と呼ぶ。日本では近年、食生活の欧米化に伴って高尿酸血症を発症する人が増加しており、特に中高年の男性にその傾向が見られる。高尿酸血症は通風や動脈硬化、腎機能低下等の様々な疾患の原因となることが分かっている。尿酸はプリン骨格と呼ばれる共通の構造を有するプリン体が代謝されて生じる化合物である。このプリン体は体細胞の新陳代謝やＡＴＰ、ＧＴＰなどのエネルギー源、日々摂取する食事などに由来しており、特に食事由来のプリン体は肉や魚、ビールなどに多く含まれている（非特許文献１）。 A condition in which the concentration of uric acid in the blood is abnormally high (7.0 mg / dL or more in both sexes) is called hyperuricemia. In recent years, in Japan, the number of people who develop hyperuricemia due to the westernization of eating habits has been increasing, and the tendency is particularly observed in middle-aged and elderly men. It is known that hyperuricemia causes various diseases such as gout, arteriosclerosis, and renal dysfunction. Uric acid is a compound formed by metabolizing purines having a common structure called a purine skeleton. This purine body is derived from the metabolism of somatic cells, energy sources such as ATP and GTP, and daily meals, etc. In particular, dietary purine bodies are abundant in meat, fish, beer, etc. Reference 1).
高尿酸血症の治療薬は尿酸を作らないようにする尿酸生成抑制薬と尿酸を外に出す尿酸排泄促進薬の２種類に分類される。前者は、プリン体を尿酸に分解する過程で必要な酵素であるキサンチンオキシターゼ（ＸＯ）を阻害する事で尿酸生成を抑えるものである。一方、後者は腎臓の近位尿細管に存在するＵＲＡＴ１と呼ばれる尿酸再吸収を行う尿酸トランスポーター分子を阻害する事で、尿酸排出を促進するものである。 Drugs for treating hyperuricemia are classified into two types: uric acid production inhibitors that prevent the production of uric acid, and uric acid excretion enhancers that release uric acid. The former suppresses uric acid production by inhibiting xanthine oxidase (XO), a necessary enzyme in the process of decomposing purines into uric acid. On the other hand, the latter promotes uric acid excretion by inhibiting a uric acid transporter molecule called URAT1, which is present in the proximal tubule of the kidney and performs uric acid reabsorption.
ここで、一般の人が高尿酸血症を予防する為に、プリン体の含有量を低減したアルコール類等が市販されている。しかし、摂取するプリン体を低減するだけでは十分ではなく、日常的に摂取可能な、高尿酸血症を緩和する食品やサプリメントが求められており、乳酸菌やビフィズス菌が着目されている。
例として、ラクトバチルス・ガセリＰＡ−３株はプリン体の分解物であるプリンヌクレオシドをプリン塩基へと分解する活性が高く、消化菅からのプリンヌクレオシドの吸収を抑制することが分かっている（非特許文献２）。ラットを用いた試験でもラクトバチルス・ガセリＰＡ−３株は、血中の尿酸値上昇抑制効果を有することが確認されている。更に、特許文献では、ラクトバチルス・ガセリＯＬＬ２９２２株が血清尿酸値の上昇を抑えることや（特許文献１）、ビフィドバクテリウム・ロンガムＢＢ５３６株が高尿酸血症の予防剤となること（特許文献２）が報告されている。
Here, in order to prevent hyperuricemia by ordinary people, alcohols and the like having a reduced purine content are commercially available. However, it is not enough to reduce ingested purines, and there is a demand for foods and supplements that can be taken on a daily basis and that alleviate hyperuricemia, and lactic acid bacteria and bifidobacteria are attracting attention.
As an example, Lactobacillus gasseri PA-3 strain has a high activity of decomposing purine nucleosides, which are decomposed products of purines, into purine bases, and suppresses the absorption of purine nucleosides from the digestive tract (non-purine nucleosides). Patent Document 2). Tests using rats also confirmed that Lactobacillus gasseri PA-3 strain has an effect of suppressing an increase in blood uric acid level. Furthermore, in the patent literature, Lactobacillus gasseri OLL2922 strain suppresses an increase in serum uric acid level (Patent Document 1), and Bifidobacterium longum BB536 strain becomes a preventive agent for hyperuricemia (Patent Document 1). 2) has been reported.
既存の報告では、ラクトバチルス・ガセリＯＬＬ２９２２株やビフィドバクテリウム・ロンガムＢＢ５３６が血清尿酸値を抑える傾向があることが報告されているが、その他の乳酸菌やビフィズス菌についての報告は無い。そこで、本発明では上記２つの菌株以外にプリン体の分解能を有する乳酸菌やビフィズス菌を提供する事を課題とする。 Existing reports have reported that Lactobacillus gasseri OLL2922 strain and Bifidobacterium longum BB536 tend to suppress serum uric acid levels, but there are no reports on other lactic acid bacteria or bifidobacteria. Therefore, an object of the present invention is to provide a lactic acid bacterium and a bifidobacterium having purine resolution in addition to the above two strains.
本発明は、下記のいずれかの構成からなる発明である。
（１）下記（A)〜（D)のうちいずれかに属する１又は２種以上の菌、該菌含有物および／またはその処理物を有効成分とする血中尿酸値低減剤。
（A) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum）
（B) ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacterium animalis ssp.animalis）
（C) ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）
（D) ビフィドバクテリウム・インファンティス（Bifidobacterium infantis）
（２）下記（E)〜（J)のうちいずれか１つ及び又は２種以上の菌株、該菌株含有物および／またはその処理物を有効成分とする血中尿酸値低減剤。
（E) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum ）SBT2908株（FERM P-10138）
（F) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum） 基準株
（G) ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacterium animalis ssp.animalis）基準株
（H) ラクトバチルス・ヘルベティカス（Lactobacillus helveticus） SBT2161株（NITE ABP-01707）
（I) ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）SBT2171株（FERM BP-5445）
（J）ビフィドバクテリウム・インファンティス（Bifidobacterium infantis） 基準株
（３）（１）または（２）に記載の血中尿酸値低減剤を含むことを特徴とする血中尿酸値低減用飲食品、血中尿酸値低減用栄養組成物、又は血中尿酸値低減用医薬品。
The present invention is an invention having any one of the following configurations.
(1) A blood uric acid level reducing agent comprising one or more bacteria belonging to any of the following (A) to (D), a substance containing the bacteria and / or a processed product thereof as an active ingredient.
(A) Bifidobacterium pseudolongum
(B) Bifidobacterium animalis subspecies animalis
(C) Lactobacillus helveticus
(D) Bifidobacterium infantis
(2) A blood uric acid level reducing agent comprising, as an active ingredient, any one and / or two or more of the following (E) to (J), and a strain-containing substance and / or a processed product thereof.
(E) Bifidobacterium pseudolongum SBT2908 strain (FERM P-10138)
(F) Bifidobacterium pseudolongum (B) Reference strain (G) Bifidobacterium animalis subspecies animalis (Bifidobacterium animalis ssp.animalis) reference strain (H) Lactobacillus helveticus ) SBT2161 strain (NITE ABP-01707)
(I) Lactobacillus helveticus SBT2171 strain (FERM BP-5445)
(J) Reference strain of Bifidobacterium infantis
(3) A food and drink for reducing blood uric acid level, a nutritional composition for reducing blood uric acid level, or a blood uric acid level, which comprises the blood uric acid level reducing agent according to (1) or (2). Drugs for reduction.
本発明は、食経験のあるビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum）やビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacterium animalis ssp.animalis）やラクトバチルス・ヘルベティカス（Lactobacillus helveticus）やビフィドバクテリウム・インファンティス（Bifidobacterium infantis）に属する菌を用いる事によって、プリンヌクレオシドをプリン塩基へと分解出来るので、プリンヌクレオシドが消化管から吸収される事を抑制する。その結果、血中尿酸値が低減されるので、高尿酸血症、通風や動脈硬化、腎機能低下などの疾患の予防または治療に有効である。 The present invention relates to Bifidobacterium pseudolongum (Bifidobacterium animalis subsp. By using a bacterium belonging to Bifidobacterium infantis, purine nucleosides can be decomposed into purine bases, thereby suppressing purine nucleosides from being absorbed from the digestive tract. As a result, the uric acid level in the blood is reduced, which is effective in preventing or treating diseases such as hyperuricemia, ventilation, arteriosclerosis, and decreased renal function.
本発明は、上記した課題を解決するためになされたものであって、本発明者らは、目的とする乳酸菌をスクリーニングするに際し、次のような基準を新たに設定し目的に合致する株を選定した。すなわち、本発明者らは、数多くの乳酸菌及びビフィズス菌のうち、プリンヌクレオシドをプリン塩基へと分解する能力の高いものを得る為に、菌株の選定につき鋭意研究を重ねた。スクリーニングの結果、上記条件に合致する菌種として、ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum）、ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacterium animalis ssp.animalis）、ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）、ビフィドバクテリウム・インファンティス（Bifidobacterium infantis）に属する乳酸菌が得られた。このうちでも特に以下の菌株が好ましい。
なお、ＦＥＲＭ Ｐ−１０１３８、ＮＩＴＥ ＢＰ−０１７０７、ＦＥＲＭ ＢＰ−５４４５は、下記の寄託番号により独立行政法人産業技術総合研究所特許微生物寄託センターに寄託されている。ＡＴＣＣ２５５２６、ＡＴＣＣ２５５２７はAmerican Type Culture Collectionから入手可能である。ＪＣＭ１２２２は理化学研究所 微生物材料開発室から入手可能である。
なお、本発明では、乳酸菌及びビフィズス菌を合わせて乳酸菌ということがあり、特に区別しない限りは両方を含む意味で用いる。
The present invention has been made in order to solve the above-mentioned problems, and the present inventors, when screening for a target lactic acid bacterium, set a new standard as follows and strains that meet the purpose. Selected. That is, the present inventors have conducted intensive research on the selection of strains in order to obtain, from among many lactic acid bacteria and bifidobacteria, those having a high ability to degrade purine nucleosides into purine bases. As a result of the screening, as strains meeting the above conditions, Bifidobacterium pseudolongum (Bifidobacteriumu pseudolongum), Bifidobacterium animalis subspecies animalis (Bifidobacterium animalis ssp.animalis), Lactobacillus helveticus ( Lactobacillus helveticus) and lactic acid bacteria belonging to Bifidobacterium infantis were obtained. Among these, the following strains are particularly preferred.
FERM P-10138, NITE BP-01707, and FERM BP-5445 have been deposited at the National Institute of Advanced Industrial Science and Technology, Patent Microorganisms Depositary under the following deposit numbers. ATCC 25526 and ATCC 25527 are available from the American Type Culture Collection. JCM1222 is available from the RIKEN Microbial Materials Development Office.
In the present invention, a lactic acid bacterium and a bifidobacterium are sometimes collectively referred to as a lactic acid bacterium, and are used to include both unless otherwise specified.
菌株
ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株（ＦＥＲＭ Ｐ−１０１３８）
ビフィドバクテリウム・シュードロンガム基準株（ＡＴＣＣ２５５２６）
ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス基準株（ＡＴＣＣ２５５２７）
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株（ＮＩＴＥ ＢＰ−０１７０７）
ラクトバチルス・ヘルベティカス ＳＢＴ２１７１株（ＦＥＲＭ ＢＰ−５４４５）
ビフィドバクテリウム・インファンティス基準株（ＪＣＭ１２２２）
Strain Bifidobacterium pseudolongum SBT2908 strain (FERM P-10138)
Bifidobacterium pseudolongum reference strain (ATCC 25526)
Bifidobacterium animalis subspecies animalis reference strain (ATCC 25527)
Lactobacillus helveticus SBT2161 strain (NITE BP-01707)
Lactobacillus helveticus SBT2171 strain (FERM BP-5445)
Bifidobacterium infantis reference strain (JCM1222)
本発明のビフィドバクテリウム・シュードロンガム、ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス、ラクトバチルス・ヘルベティカス、ビフィドバクテリウム・インファンティスに属する菌を培養する培地としては、乳培地または乳成分を含む培地、これを含まない半合成培地等、種々の培地を用いることができる。このような培地としては、脱脂乳を還元して加熱殺菌した還元脱脂乳培地を例示することができる。
培養法は、静置培養またはｐＨを一定にコントロールした中和培養で行うが、菌が良好
に生育する条件であれば特に培養法に制限はない。
As a medium for culturing bacteria belonging to Bifidobacterium pseudolongum, Bifidobacterium animalis subspecies animaris, Lactobacillus helveticus, Bifidobacterium infantis, a milk medium or Various media such as a medium containing a milk component and a semi-synthetic medium not containing the same can be used. Examples of such a medium include a reduced skim milk medium obtained by reducing skim milk and heat-sterilizing the skim milk.
The culture method is a static culture or a neutralization culture in which the pH is controlled at a constant value. However, the culture method is not particularly limited as long as the bacteria can grow well.
本発明は、上述のようにして得られる培養物及び／または菌体を有効成分とする。また
乾燥した粉末を有効成分としてもよい。これらの乾燥は凍結乾燥で行なうことが菌体を変
質させることなく乾燥することができるので好ましい。
これらの有効成分は経口摂取することが望ましい。また、これらの粉末は乳糖等の適当
な賦形剤と混合し、粉剤、錠剤、丸剤、カプセル剤または粒剤等として経口投与すること
ができる。投与量は、投与対象者の症状、年齢等を考慮してそれぞれ個別に適宜決定され
る。
In the present invention, a culture and / or a cell obtained as described above is used as an active ingredient. Dried powder may be used as an active ingredient. It is preferable that the drying is performed by freeze-drying because the cells can be dried without deteriorating the cells.
These active ingredients are preferably taken orally. These powders can be mixed with a suitable excipient such as lactose and administered orally as powders, tablets, pills, capsules or granules. The dose is appropriately determined individually in consideration of the symptoms, age and the like of the subject.
また、本発明の有効成分は、飲食品の製造工程中に原料に添加してもよい。飲食品としてはどのような飲食品でもよく、その例として、乳飲料、発酵乳、チーズ、果汁飲料、ゼリー、キャンディー、乳製品、マヨネーズ等の卵加工品、バターケーキ等の菓子パン類等の食品を挙げることができる。また、マイクロカプセル等の従来技術を採用して、加熱を避ける手段を講じてもよい。
さらにまた、本発明における飲食品は、前述した菌を使用して乳酸発酵を行なって製造されたヨーグルト等であっても良い。
Further, the active ingredient of the present invention may be added to raw materials during the production process of food and drink. The food or drink may be any food or drink, such as milk drink, fermented milk, cheese, fruit drink, jelly, candy, dairy products, processed egg products such as mayonnaise, and confectionery bread such as butter cake. Can be mentioned. In addition, conventional technology such as microcapsules may be employed to take measures to avoid heating.
Furthermore, the food or drink in the present invention may be yogurt or the like produced by performing lactic acid fermentation using the above-mentioned bacteria.
本発明において、プリン体とはプリン骨格を持つ物質の総称で、プリン塩基（アデニン、グアニン、ヒポキサンチン）、プリンヌクレオシド（アデノシン、イノシン、グアノシン）、プリンヌクレオチド（ＡＴＰ、ＡＤＰ、ＡＭＰ、ＩＴＰ、ＩＤＰ、ＩＭＰ、ＧＭＰ、ＧＤＰ、ＧＴＰ）等の総称である。 In the present invention, purines are a general term for substances having a purine skeleton, and include purine bases (adenine, guanine, hypoxanthine), purine nucleosides (adenosine, inosine, guanosine), purine nucleotides (ATP, ADP, AMP, ITP, IDP). , IMP, GMP, GDP, GTP).
本発明においてプリン体分解能とは、プリンヌクレオシドを分解する能力を言う。プリンヌクレオシド（アデノシン、イノシン、グアノシン）を分解する事で、プリン塩基（アデニン、グアニン、ヒポキサンチン）となる以外に、更に別の化合物へと変換される事も本発明に含む。 In the present invention, purine resolution refers to the ability to degrade purine nucleosides. The present invention also includes that by decomposing purine nucleosides (adenosine, inosine, guanosine), the compound is converted into another compound in addition to a purine base (adenine, guanine, hypoxanthine).
生体内におけるプリン体の代謝は公知である。プリンヌクレオチドであるＡＭＰは代謝によりプリンヌクレオシドであるアデノシンとなり、アデノシンは代謝によりプリン塩基であるアデニンとなる。同様に、プリンヌクレオチドであるＩＭＰはプリンヌクレオシドであるイノシンとなり、イノシンはプリン塩基であるヒポキサンチンとなる。また、プリンヌクレオチドであるＧＭＰはプリンヌクレオシドであるグアノシンとなり、グアノシンはプリン塩基であるグアニンとなる。グアニンやヒポキサンチンは更に代謝され、最終的に尿酸となる。 Purine metabolism in vivo is known. AMP, a purine nucleotide, is metabolized to adenosine, a purine nucleoside, and adenosine is adenine, a purine base, by metabolism. Similarly, IMP, a purine nucleotide, becomes inosine, a purine nucleoside, and inosine becomes hypoxanthine, a purine base. GMP, which is a purine nucleotide, becomes guanosine, which is a purine nucleoside, and guanosine becomes guanine, which is a purine base. Guanine and hypoxanthine are further metabolized to ultimately become uric acid.
プリンヌクレオチドやプリンヌクレオシドは消化管において吸収されやすい。その結果、血中にプリンヌクレオチドやプリンヌクレオシドが増加する。血中でプリンヌクレオチドやプリンヌクレオシドの上記代謝が進むことにより、血中尿酸値が上昇し、高尿酸血症となる。一方本発明の血中尿酸値低減剤を用いる事により、消化管に吸収される前にプリンヌクレオシドが分解され、プリンヌクレオチドやプリンヌクレオシドと比較して消化管に吸収されにくいプリン塩基等に変換される。その結果、血中のプリンヌクレオチドやプリンヌクレオシドが低下し、代謝物であるプリン体濃度が低下する事により、血中尿酸値の上昇が防止される。 Purine nucleotides and purine nucleosides are easily absorbed in the digestive tract. As a result, purine nucleotides and purine nucleosides increase in blood. As the above-mentioned metabolism of purine nucleotides and purine nucleosides proceeds in blood, blood uric acid level increases, resulting in hyperuricemia. On the other hand, by using the blood uric acid level reducing agent of the present invention, purine nucleosides are decomposed before being absorbed into the digestive tract, and are converted into purine bases and the like which are less easily absorbed into the digestive tract as compared with purine nucleotides and purine nucleosides. You. As a result, purine nucleotides and purine nucleosides in blood decrease, and the concentration of metabolite purine decreases, thereby preventing an increase in blood uric acid level.
以下に、実施例及び試験例を示し、本発明についてより詳細に説明するが、これらは単に例示するのみであり、本発明はこれらによって何ら限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but these are merely examples, and the present invention is not limited thereto.
［試験例１］
［プリンヌクレオシド分解能の評価］
各乳酸菌と、プリンヌクレオシドとしてアデノシン、イノシン、グアノシンを反応させ、反応前後でのプリンヌクレオシド量を測定する事により、各乳酸菌のプリンヌクレオシド分解能を評価した。
［１．試料の準備］
表１に示す９株を供試菌として使用した。乳酸菌はＭＲＳ液体培地、ビフィズス菌はＧＡＭ＋１％Ｇｌｃ液体培地を用いて３７℃、１６時間静置培養した。遠心分離（１，９１２×ｇ，４℃，１５ｍｉｎ）により菌体を回収し、滅菌ＰＢＳを用いて３回洗浄した。回収した菌体を１００ｍＭ リン酸カリウム緩衝液（１ｍＭ ＭｇＳＯ４添加、ｐＨ７）に再懸濁した。
[Test Example 1]
[Evaluation of purine nucleoside resolution]
Each lactic acid bacterium was reacted with adenosine, inosine, and guanosine as purine nucleosides, and the purine nucleoside resolution of each lactic acid bacterium was evaluated by measuring the amount of purine nucleoside before and after the reaction.
[1. Preparation of sample]
Nine strains shown in Table 1 were used as test bacteria. Lactic acid bacteria were cultured in an MRS liquid medium, and bifidobacteria were cultured in a GAM + 1% Glc liquid medium at 37 ° C. for 16 hours. The cells were collected by centrifugation (1,912 × g, 4 ° C., 15 min) and washed three times with sterile PBS. The collected cells were resuspended in 100 mM potassium phosphate buffer (1 mM MgSO 4 added, pH 7).
［２．プリン体分解反応］
プリンヌクレオシドとして、グアノシン、イノシン、アデノシンを使用した。１．２５ ｍＭの各種プリンヌクレオシドを含有する菌体懸濁液（生菌数１．０×１０９ｃｆｕ／ｍｌ程度）を調製し、３７℃にて１４０ｒｐｍ、１時間振とうした。反応上清を遠心回収（１，９１２×ｇ，４℃，１５ｍｉｎ）し、ＨＰＬＣにてプリンヌクレオシド（基質）およびプリン塩基（反応産物）を定量した。
[2. Purine decomposition reaction]
Guanosine, inosine, and adenosine were used as purine nucleosides. A cell suspension (about 1.0 × 10 9 cfu / ml viable cells) containing 1.25 mM of various purine nucleosides was prepared and shaken at 140 ° C. for 1 hour at 37 ° C. The reaction supernatant was collected by centrifugation (1,912 × g, 4 ° C., 15 min), and purine nucleoside (substrate) and purine base (reaction product) were quantified by HPLC.
［３．ＨＰＬＣ分析］
ＨＰＬＣは１２００シリーズ（アジレントテクノロジー株式会社）を使用した。溶離液Ａ（２５ｍＭ ＫＨ２ＰＯ４（０．１％ Ｍｅｔｈａｎｏｌ））で平衡化したＯＤＳカラム（Ｈｙｄｒｏｓｐｈｅｒｅ Ｃ１８ 粒子径（μｍ）Ｓ−５，細孔径４．６Ｘ２５０，品番 ＨＳ１２Ｓ０５−２５４６ＷＴ，ＹＭＣ社製）に分析サンプルを１０μｌインジェクトし、溶離液Ｂ（２５ｍＭ ＫＨ２ＰＯ４（０．１％ Ｍｅｔｈａｎｏｌ）／Ｍｅｔｈａｎｏｌ＝７５：２５Ｖ／Ｖ）の濃度勾配によってリニアグラディエントで分離溶出を行った（表２）。カラムオーブンは３０℃とし、検出はＵＶディテクター（２５４ｎｍ）を利用した。分析サンプルは、７８０μｌの溶離液Ａに反応液２００μｌおよび内部標準として２０μｌの１．５ｍｇ／ｍｌの５−ブロモウラシルを混合し、フィルターろ過（０．２２μｍ）したものを使用した。
[3. HPLC analysis]
The HPLC used was a 1200 series (Agilent Technology Co., Ltd.). ODS column (Hydrosphere C18 particle diameter (μm) S-5, pore diameter 4.6 × 250, product number HS12S05-2546WT, manufactured by YMC) equilibrated with eluent A (25 mM KH 2 PO 4 (0.1% methanol)) 10 μl of the analysis sample was injected into the column, and separation and elution were carried out with a linear gradient using a concentration gradient of eluent B (25 mM KH 2 PO 4 (0.1% methanol) / methanol = 75: 25 V / V) (Table 2). . The column oven was set at 30 ° C., and detection was performed using a UV detector (254 nm). The analysis sample used was prepared by mixing 780 μl of eluent A with 200 μl of the reaction solution and 20 μl of 1.5 mg / ml 5-bromouracil as an internal standard, followed by filtration through a filter (0.22 μm).
［４．プリンヌクレオシド分解能の評価］
各供試菌によるプリンヌクレオシドの分解率を図１に示した。今回試験した中で最も高い分解率を示したのは、ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリスＡＴＣＣ２５５２７でアニマリスの基準株であった（分解率９０％）。
また、ビフィドバクテリウム・シュードロンガムや（ＳＢＴ２９０８株、基準株（ＡＴＣＣ２５５２６））、ラクトバチルス・ヘルベティカス（ＳＢＴ２１７１株、ＳＢＴ２１６１株、基準株）にもプリン体分解能があることが示された。
一方、ラクトバチルス・ガセリ（基準株ＪＣＭ１１３１）やビフィドバクテリウム・アドセンティス（基準株ＡＴＣＣ１５７０３）にはプリン体の分解活性はほとんど認められなかった（分解率５％未満）。
[4. Evaluation of purine nucleoside resolution]
FIG. 1 shows the degradation rates of purine nucleosides by each test microorganism. The highest degradation rate tested in this experiment was Bifidobacterium animalis subspecies animalis ATCC 25527, the standard strain of animalis (90% degradation rate).
It was also shown that Bifidobacterium pseudolongum, (SBT2908 strain, reference strain (ATCC25526)) and Lactobacillus helveticus (SBT2171 strain, SBT2161 strain, reference strain) also have purine resolution.
On the other hand, in Lactobacillus gasseri (reference strain JCM1131) and Bifidobacterium adcentis (reference strain ATCC15703), almost no purinase-degrading activity was observed (degradation rate of less than 5%).
［５．プリン塩基生成量の評価］
各供試菌によるプリンヌクレオシドの分解物であるプリン塩基の生成量を図２に示した。
プリン塩基の生成量は、プリン塩基であるグアニン（Ｇ）、ヒポキサンチン（Ｈ）、アデニン（Ａ）の合成量を各分析における内部標準５−ブロモウラシル量で割った値を合算した数値（ＧＨＡ／５Ｂｕ）で示した。結果は上記４．で示したプリンヌクレオシドの分解率と相関していた。
[5. Evaluation of Purine Base Production Amount]
FIG. 2 shows the production amount of purine bases, which are degradation products of purine nucleosides, by each test microorganism.
The amount of purine base produced is a numerical value (GHA) obtained by summing the values obtained by dividing the amounts of synthesis of purine bases guanine (G), hypoxanthine (H), and adenine (A) by the amount of internal standard 5-bromouracil in each analysis. / 5Bu). The result is 4. And correlated with the degradation rate of purine nucleoside.
［実施例１．乾燥粉末］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株をそれぞれ１０％還元脱脂乳培地（１２１℃、１０分加熱）で培養し、本培養物を凍結乾燥し粉末化し、本発明の高尿酸血症予防剤を調製した。
Example 1 Dry powder]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were each reduced by 10% reduced skim milk medium (heated at 121 ° C. for 10 minutes). ), And the main culture was freeze-dried and powdered to prepare the anti-hyperuricemia agent of the present invention.
［実施例２．発酵乳］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株をそれぞれＧＡＭ＋１％Ｇｌｃ液体培地にて培養した。対数増殖期にある各培養液を、０．３％の酵母エキスを添加した１０％還元脱脂乳（１１５℃、２０分間滅菌）に１％接種し、個々マザーカルチャーを作成した。
これをヨーグルトミックス（１０％の還元脱脂乳を添加し、１００℃にて１０分間加熱したもの）に各２．５％添加して調製した。発酵は３７℃で行い、乳酸酸度０．８５に到達した時点で冷却し、発酵を終了させ、本発明の高尿酸血症予防作用を有する発酵乳を調製した。
Example 2 Fermented milk]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were each cultured in a GAM + 1% Glc liquid medium. Each culture in the logarithmic growth phase was inoculated at 1% to 10% reduced skim milk (sterilized at 115 ° C. for 20 minutes) to which 0.3% of yeast extract was added to prepare an individual mother culture.
This was prepared by adding 2.5% each to a yogurt mix (10% reduced skim milk added and heated at 100 ° C. for 10 minutes). The fermentation was performed at 37 ° C., and when the lactic acid acidity reached 0.85, the fermentation was terminated by terminating the fermentation to prepare a fermented milk having a hyperuricemia-preventing action of the present invention.
［実施例３．製剤例１］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株を、それぞれの液体培養物から対数増殖期にある菌体を、４℃、７，０００ｒｐｍで１５分間遠心分離して滅菌水による洗浄を行い、これを３回繰り返して洗浄菌体を得た。これを凍結乾燥処理して菌体粉末を得た。この菌体粉末１部に脱脂乳４部を混合し、この粉末を打錠機により１ｇずつ定法により打錠して、菌体２００ｍｇを含む錠剤を調製した。また、上記のラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株のいずれかを含有する発酵乳を凍結乾燥し、得られた粉末を用いて直接打錠した。
Example 3 Formulation Example 1]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were obtained from the respective liquid cultures in a logarithmic growth phase. Was centrifuged at 7,000 rpm for 15 minutes at 4 ° C., and washed with sterile water. This was repeated three times to obtain washed cells. This was freeze-dried to obtain a cell powder. One part of this cell powder was mixed with 4 parts of skim milk, and this powder was tableted by a tableting machine by a standard method in an amount of 1 g to prepare a tablet containing 200 mg of cells. Further, the fermented milk containing any one of the above-mentioned Lactobacillus helveticus SBT2161, Strain Lactobacillus helveticus SBT2171, Strain Bifidobacterium pseudolongum SBT2908 and the reference strain of Bifidobacterium pseudolongum is freeze-dried. Then, tableting was performed directly using the obtained powder.
［実施例５．製剤例２］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株を、それぞれＭＲＳ液体培地（Ｄｉｆｃｏ社製）５Ｌに接種後、３７℃、１８時間静置培養を行った。上記４菌株をそれぞれ脱脂乳５Ｌに接種後、３７℃、１８時間静置培養を行った。培養終了後、７，０００ｒｐｍで１５分間遠心分離を行い、培養液の１／５０量のそれぞれの濃縮菌体を得た。次いで、この濃縮菌体を脱脂粉乳１０％（重量）、グルタミン酸ソーダ１％（重量）を含む分散媒と同量混合し、ｐＨ７に調整後、凍結乾燥を行った。得られた凍結乾燥物を６０メッシュのフルイで整粒化し、凍結乾燥菌末を得た。
第１３改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記で得られた凍結乾燥菌末１ｇにラクトース（日局）４００ｇ、バレイショデンプン（日局）６００ｇを加えて均一に混合し、散剤を製造した。
Example 5 Formulation Example 2]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were each inoculated into 5 L of MRS liquid medium (manufactured by Difco). At 37 ° C. for 18 hours. After inoculating 5 L of skim milk with each of the above four strains, static culture was performed at 37 ° C. for 18 hours. After the completion of the culture, centrifugation was performed at 7,000 rpm for 15 minutes to obtain 1/50 volume of each concentrated bacterial cell of the culture solution. Next, the concentrated cells were mixed with the same amount of a dispersion medium containing 10% (by weight) of skim milk powder and 1% (by weight) of sodium glutamate, adjusted to pH 7, and lyophilized. The obtained freeze-dried product was sized with a 60-mesh sieve to obtain freeze-dried bacterial powder.
According to the 13th revision of the Japanese Pharmacopoeia, instructions for preparations in the Japanese Pharmacopoeia, the general rule of "powder", 400 g of lactose (JP) and 600 g of potato starch (JP) are added to 1 g of the freeze-dried bacterial powder obtained above and mixed uniformly. To produce a powder.
［実施例６．製剤例３］
次の配合により高尿酸血症予防剤を製造し
（１）ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株のそれぞれの脱脂粉乳培地における培養物の凍結乾燥物５０ｇ、
（２）ラクトース９０ｇ、
（３）コーンスターチ２９ｇ、
（４）ステアリン酸マグネシウム１ｇ、
この混合物を圧縮錠剤機により圧縮して、１錠あたり有効成分を４０ ｍｇ含有する錠剤１００個をそれぞれ製造した。
Example 6 Formulation Example 3]
A hyperuricemia-preventing agent was produced by the following formulation (1) Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum standard Freeze-dried 50 g of the culture in each skim milk medium of the strain,
(2) lactose 90g,
(3) 29 g of corn starch,
(4) 1 g of magnesium stearate,
This mixture was compressed using a compression tablet machine to produce 100 tablets each containing 40 mg of the active ingredient per tablet.
［実施例７．製剤例４］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株をそれぞれホエー培地（０．５％酵母エキス、０．１％トリプチケースペプトン添加）で培養後遠心分離で菌体を回収した。この培養物１ｇを乳糖５ｇと混合し顆粒状に成形して顆粒剤を得た。
Example 7 Formulation Example 4]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were each added to a whey medium (0.5% yeast extract, 0.1% % Trypticase peptone), and the cells were collected by centrifugation. 1 g of this culture was mixed with 5 g of lactose and formed into granules to obtain granules.
［実施例８．飲料の製造］
洗浄菌体の凍結乾燥粉末をラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株又はビフィドバクテリウム・シュードロンガム基準株がそれぞれ１０８個以上含まれるように２００ｍｌの牛乳と混合して、本発明の高尿酸血症予防剤入り飲料を得た。良好な風味を有していた。
[Embodiment 8. Production of beverages]
Contain lyophilized powder washed cells SBT2161 strain Lactobacillus helveticus, Lactobacillus helveticus SBT2171 strain, Bifidobacterium shoe drone gum SBT2908 strain or Bifidobacterium shoe drone gum reference strains each 10 8 or more The mixture was mixed with 200 ml of milk to obtain a hyperuricemia-preventing agent-containing beverage of the present invention. It had a good flavor.
［実施例９．ヨーグルトの製造］
ラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株及びビフィドバクテリウム・シュードロンガム基準株をそれぞれヨーグルトミックス（生乳に２％脱脂乳を添加し、１００℃、１０分加熱した）に接種し、２０℃で２４時間培養した。紙カップに充填し冷却後、ヨーグルトとした製品中のラクトバチルス・ヘルベティカスＳＢＴ２１６１株、ラクトバチルス・ヘルベティカスＳＢＴ２１７１株、ビフィドバクテリウム・シュードロンガムＳＢＴ２９０８株又はビフィドバクテリウム・シュードロンガム基準株の生菌数濃度は、１００ｇ当たり１０８個以上であった。
[Embodiment 9. Production of yogurt]
Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain and Bifidobacterium pseudolongum reference strain were each added to yogurt mix (2% skim milk was added to raw milk, (Heated at 100 ° C. for 10 minutes) and cultured at 20 ° C. for 24 hours. After filling into a paper cup and cooling, yogurt is used to produce Lactobacillus helveticus SBT2161 strain, Lactobacillus helveticus SBT2171 strain, Bifidobacterium pseudolongum SBT2908 strain or Bifidobacterium pseudolongum reference strain The bacterial concentration was at least 10 8 per 100 g.
本発明の高尿酸血症予防剤によれば、血中尿酸値が低減されるので、通風や動脈硬化、腎機能低下などの疾患の予防または治療に有効である。 ADVANTAGE OF THE INVENTION According to the hyperuricemia prevention agent of this invention, since the uric acid level in blood is reduced, it is effective in prevention or treatment of diseases, such as ventilation, arteriosclerosis, and renal function decline.
［寄託生物材料への言及］
（１）ビフィドバクテリウム・シュードロンガム（Bifidobacterium pseudolongum）ＳＢＴ２９０８
イ 当該生物材料を寄託した寄託機関の名称及び住所
独立行政法人 産業技術総合研究所 特許生物寄託センター
日本国茨城県つくば市東１丁目１番３号
ロ イの寄託機関に生物材料を寄託した日付
昭和６３年７月２０日（１９８８年７月２０日）（原寄託日）
ハ イの寄託機関が寄託について付した受託番号
ＦＥＲＭ Ｐ−１０１３８
（２）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）ＳＢＴ２１６１
イ 当該生物材料を寄託した寄託機関の名称及び住所
独立行政法人製品評価技術基盤機構特許微生物寄託センター
千葉県木更津市かずさ鎌足２−５−８
ロ イの寄託機関に生物材料を寄託した日付
２０１３年９月１８日
ハ イの寄託機関が寄託について付した受託番号
ＮＩＴＥ ＢＰ−０１７０７
（３）ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）ＳＢＴ２１７１
イ 当該生物材料を寄託した寄託機関の名称及び住所
独立行政法人 産業技術総合研究所 特許生物寄託センター
日本国茨城県つくば市東１丁目１番３号
ロ イの寄託機関に生物材料を寄託した日付
平成６年６月２２日（１９９４年６月２２日）（原寄託日）
平成８年３月６日（１９９６年３月６日）（原寄託によりブタペスト条約に基づく寄託への移管日）
ハ イの寄託機関が寄託について付した受託番号
ＦＥＲＭ ＢＰ−５４４５
[Reference to deposited biological material]
(1) Bifidobacterium pseudolongum SBT2908
B.Name and address of the depositary institution that deposited the biological material The National Institute of Advanced Industrial Science and Technology (AIST) Patent Organism Depositary Center 1-3-1 Higashi, Tsukuba-shi, Ibaraki, Japan July 20, 1988 (July 20, 1988) (Original deposit date)
Accession number FERM P-10138 assigned by the depositary institution for the deposit
(2) Lactobacillus helveticus SBT2161
B. Name and address of the depository institution that deposited the biological material 2-5-8 Kazusa Kamatari, Kisarazu-shi, Chiba Pref.
Lo. Deposit date of biological material to the depositary institution September 18, 2013 Accession number NITE BP-01707 assigned to the deposit by the hi depositary institution
(3) Lactobacillus helveticus SBT2171
B. The name and address of the depositary institution that deposited the biological material The National Institute of Advanced Industrial Science and Technology (AIST) June 22, 1994 (June 22, 1994) (Original deposit date)
March 6, 1996 (March 6, 1996) (Transfer date to original deposit based on the Budapest Treaty)
Accession number FERM BP-5445 assigned by the depositary institution for the deposit.
Claims (3)
（A) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum）
（B) ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacte rium animalis ssp.animalis）
（C) ラクトバチルス・ヘルベティカス（Lactobacillus helveticus）
（D) ビフィドバクテリウム・インファンティス（Bifidobacterium infantis） A blood uric acid level-reducing agent comprising one or more bacteria belonging to any of the following (A) to (D), a substance containing the bacteria and / or a culture thereof as an active ingredient.
(A) Bifidobacterium pseudolongum
(B) Bifidobacterium animalis subspecies animalis (Bifidobacterium animalis ssp.animalis)
(C) Lactobacillus helveticus
(D) Bifidobacterium infantis
（E) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum ）SBT 2908株（FERM P-10138）
（F) ビフィドバクテリウム・シュードロンガム（Bifidobacteriumu pseudolongum） 基準株
（G) ビフィドバクテリウム・アニマリス・サブスピーシーズ・アニマリス（Bifidobacte rium animalis ssp.animalis）基準株
（H) ラクトバチルス・ヘルベティカス（ Lactobacillus helveticus）SBT2161株 (NITE BP-01707)
（I) ラクトバチルス・ヘルベティカス（Lactobacillus helveticus ）SBT2171株 (FERM BP-5445)
（J）ビフィドバクテリウム・インファンティス（Bifidobacterium infantis）基準株 A blood uric acid level reducing agent comprising , as an active ingredient, one or more strains of any one of the above (E) to (J), and a strain-containing substance and / or a culture thereof .
(E) Bifidobacterium pseudolongum SBT 2908 strain (FERM P-10138)
(F) Bifidobacterium pseudolongum reference strain
(G) Bifidobacterium animalis subspecies animalis (Bifidobacterium animalis ssp.animalis) reference strain (H) Lactobacillus helveticus SBT2161 strain (NITE B P-01707)
(I) Lactobacillus helveticus SBT2171 strain (FERM BP-5445)
(J) Bifidobacterium infantis reference strain
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015153508A JP6654824B2 (en) | 2015-08-03 | 2015-08-03 | Blood uric acid level reducer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015153508A JP6654824B2 (en) | 2015-08-03 | 2015-08-03 | Blood uric acid level reducer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017031102A JP2017031102A (en) | 2017-02-09 |
| JP6654824B2 true JP6654824B2 (en) | 2020-02-26 |
Family
ID=57987739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015153508A Active JP6654824B2 (en) | 2015-08-03 | 2015-08-03 | Blood uric acid level reducer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6654824B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2017438436B2 (en) * | 2017-10-31 | 2022-01-13 | Morinaga Milk Industry Co., Ltd. | Muscle-building composition |
| CN111195266B (en) * | 2019-12-20 | 2022-11-01 | 微康益生菌(苏州)股份有限公司 | Probiotic composition with effect of relieving hyperuricemia and application thereof |
| JP7096933B1 (en) * | 2021-06-10 | 2022-07-06 | 康品科技有限公司 | Use of Lactobacillus plantarum BFA-LA4 strain and its Lactobacillus plantarum BFA-LA4 strain having a uric acid level lowering effect |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02195872A (en) * | 1988-08-12 | 1990-08-02 | Snow Brand Milk Prod Co Ltd | Method for preparing protoplast of bifidobacterium |
| US9655932B2 (en) * | 2002-03-13 | 2017-05-23 | Kibow Biotech, Inc. | Composition and method for preventing or treating gout or hyperuricemia |
| JP2009143820A (en) * | 2007-12-12 | 2009-07-02 | Tsujido Chemical Corp | Preventing or improving agent of hyperuricemia |
| JP6491422B2 (en) * | 2013-09-26 | 2019-03-27 | 雪印メグミルク株式会社 | Immune disease preventive |
-
2015
- 2015-08-03 JP JP2015153508A patent/JP6654824B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2017031102A (en) | 2017-02-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101450511B1 (en) | Lactic acid bacteria having action of lowering blood uric acid level | |
| KR101584380B1 (en) | Lactic acid bacterium having effect of lowering blood uric acid level | |
| JP5237581B2 (en) | Lactic acid bacteria with action to reduce blood uric acid level | |
| EP1972208A1 (en) | Composition for improving intestinal microflora | |
| CN102747004B (en) | Lactic acid bacteria with effect of uric acid level reducing in blood | |
| JP6637419B2 (en) | Lactic acid bacteria inhibiting purine absorption and uses thereof | |
| EP3342853B1 (en) | Intestinal bacteria butyribacter intestini | |
| JP6654824B2 (en) | Blood uric acid level reducer | |
| JP5597237B2 (en) | Lactic acid bacteria with action to reduce blood uric acid level | |
| CN113637603B (en) | Lactobacillus entericus and application thereof | |
| JP6782166B2 (en) | Lactic acid bacteria capable of taking up purines and their uses | |
| WO2020203792A1 (en) | Composition for converting skeletal muscle to slow muscle | |
| JP2003252770A (en) | Agent for prevention, improvement and treatment of diabetic complication | |
| EP3511406A1 (en) | Faecalibacterium longum and application thereof | |
| CA2851018C (en) | Lactic acid bacteria having action of lowering blood uric acid level | |
| TWI405849B (en) | Lactic acid bacteria having a function of lowering uric acid in blood | |
| TWI479020B (en) | Lactic acid bacteria having a function of lowering uric acid in blood |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150804 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180720 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190703 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190830 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191024 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200129 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200131 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6654824 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |