JPH04208226A - Lipid metabolic improver - Google Patents
Lipid metabolic improverInfo
- Publication number
- JPH04208226A JPH04208226A JP2330533A JP33053390A JPH04208226A JP H04208226 A JPH04208226 A JP H04208226A JP 2330533 A JP2330533 A JP 2330533A JP 33053390 A JP33053390 A JP 33053390A JP H04208226 A JPH04208226 A JP H04208226A
- Authority
- JP
- Japan
- Prior art keywords
- cholesterol
- lipid
- extraction residue
- active ingredient
- lactic acid
- 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.)
- Granted
Links
- 150000002632 lipids Chemical class 0.000 title abstract description 24
- 230000002503 metabolic effect Effects 0.000 title abstract 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 241000186660 Lactobacillus Species 0.000 claims abstract description 8
- 229940039696 lactobacillus Drugs 0.000 claims abstract description 8
- 238000003809 water extraction Methods 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 6
- 239000004310 lactic acid Substances 0.000 claims abstract description 6
- 230000037356 lipid metabolism Effects 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 108091005804 Peptidases Proteins 0.000 claims description 8
- 102000035195 Peptidases Human genes 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 claims description 5
- 244000199866 Lactobacillus casei Species 0.000 claims description 4
- 235000013958 Lactobacillus casei Nutrition 0.000 claims description 4
- 229940017800 lactobacillus casei Drugs 0.000 claims description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 36
- 210000002966 serum Anatomy 0.000 abstract description 13
- 235000012000 cholesterol Nutrition 0.000 abstract description 11
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 9
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 abstract description 4
- 235000002017 Zea mays subsp mays Nutrition 0.000 abstract description 4
- 235000005822 corn Nutrition 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 238000009825 accumulation Methods 0.000 abstract description 3
- 239000001963 growth medium Substances 0.000 abstract description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract description 2
- 239000008103 glucose Substances 0.000 abstract description 2
- 230000002440 hepatic effect Effects 0.000 abstract description 2
- 241000304886 Bacilli Species 0.000 abstract 2
- 241000209149 Zea Species 0.000 abstract 2
- 230000000813 microbial effect Effects 0.000 abstract 2
- 239000000725 suspension Substances 0.000 abstract 2
- 238000012258 culturing Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 21
- 239000000203 mixture Substances 0.000 description 16
- 210000004185 liver Anatomy 0.000 description 11
- 230000001580 bacterial effect Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000029142 excretion Effects 0.000 description 6
- 210000003608 fece Anatomy 0.000 description 6
- 235000009200 high fat diet Nutrition 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000000378 dietary effect Effects 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 241000186000 Bifidobacterium Species 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229930182558 Sterol Natural products 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003613 bile acid Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000002550 fecal effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 235000000891 standard diet Nutrition 0.000 description 3
- 150000003432 sterols Chemical class 0.000 description 3
- 235000003702 sterols Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000021050 feed intake Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 229940127328 Cholesterol Synthesis Inhibitors Drugs 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VRAHPESAMYMDQI-UHFFFAOYSA-N Nicomol Chemical compound C1CCC(COC(=O)C=2C=NC=CC=2)(COC(=O)C=2C=NC=CC=2)C(O)C1(COC(=O)C=1C=NC=CC=1)COC(=O)C1=CC=CN=C1 VRAHPESAMYMDQI-UHFFFAOYSA-N 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940070021 anabolic steroids Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000005686 eating Nutrition 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229950001071 nicomol Drugs 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、血清脂質上昇抑制作用、肝臓脂質上昇抑制作
用、ステロール排泄促進作用等を有する脂質代謝改善剤
に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a lipid metabolism improving agent having an effect of suppressing serum lipid increase, a hepatic lipid increase suppressing effect, a sterol excretion promoting effect, and the like.
近年、循環器疾患による死亡率は年々増加しており、心
筋梗塞、脳梗塞など動脈硬化に起因した疾患を合わせる
と、成人死亡原因の第−位を占めている。In recent years, the mortality rate due to circulatory diseases has been increasing year by year, and when combined with diseases caused by arteriosclerosis such as myocardial infarction and cerebral infarction, they are the leading cause of death among adults.
動脈硬化の原因としては様々のものがあるが、血清脂質
、特に血清コレステロール値の上昇が最も重要な危険因
子の一つとされている。Although there are various causes of arteriosclerosis, an increase in serum lipids, especially serum cholesterol levels, is considered to be one of the most important risk factors.
血清コレステロール値上昇の原因としてはまず遺伝的な
疾患がある。この場合、重篤な患者に対しては食事療法
と同時にコレステロール合成阻害剤、ニコモール、クロ
フィブレート、イオン交換樹脂、蛋白同化ステロイド等
の薬剤が使用されているが、これらの薬剤は、胛前性、
胃腸障害、発癌性等の副作用がある。Genetic diseases are the primary cause of elevated serum cholesterol levels. In this case, for seriously ill patients, drugs such as cholesterol synthesis inhibitors, nicomol, clofibrate, ion exchange resins, and anabolic steroids are used at the same time as dietary therapy; sex,
It has side effects such as gastrointestinal disorders and carcinogenicity.
血清コレステロール値上昇のもう一つの大きな原因とし
て、近年の食生活の変化にともなう脂肪の過剰摂取が挙
げられており、これは、若年金層にも顕著になりつつあ
る。食事性の高コレステロール血症の場合、通常は重篤
な高コレステロール血症には至らないが、若齢期より血
管に徐々にコレステロールが蓄積し、成人に至って動脈
硬化をひき起こすことが問題であり、高トリグリセリド
血症とあいまって、心筋梗塞や脳梗塞を招く危険性があ
る。この種の高脂血症に対しては、副作用があるなど問
題の多い薬物療法よりも、脂質摂取量を適正範囲に制限
した食事療法が重視される。しかしながら、食事制限は
精神的苦痛を伴うとともに食生活の楽しみをうばうため
厳格な実施は困難であり、効果には限界があることが多
い。Another major cause of elevated serum cholesterol levels is excessive fat intake due to recent changes in dietary habits, and this is becoming more noticeable among young adults. Dietary hypercholesterolemia does not usually lead to severe hypercholesterolemia, but the problem is that cholesterol gradually accumulates in blood vessels from a young age, leading to arteriosclerosis in adulthood. When combined with hypertriglyceridemia, there is a risk of myocardial infarction or cerebral infarction. For this type of hyperlipidemia, dietary therapy that limits fat intake to an appropriate range is more important than drug therapy, which has many problems such as side effects. However, dietary restrictions are difficult to implement strictly because they cause mental pain and take away the enjoyment of eating, and their effectiveness is often limited.
血清中に過剰に存在するコレステロールは血管壁に蓄積
して動脈硬化を招くが、コレステロールが肝臓に取り込
まれたのちそこに蓄積されることなく胆汁酸に変換され
るかそのままの形で腸管に放出され、糞便をともに体外
に排泄されるならば、体内コレステロールのプールも低
下し、上記機構による動脈硬化は予防される。そこで、
血清コレステロール値の低下作用たけでなく肝臓コレス
テロール値低下作用および胆汁酸排泄促進作用を併せ持
つものが期待されているが、従来、単独でそのような三
つの作用を示すものは知られていない。Excessive cholesterol in serum accumulates on the walls of blood vessels, leading to arteriosclerosis, but once cholesterol is taken into the liver, it is converted to bile acids without being accumulated there, or released into the intestinal tract as is. If the blood and feces are excreted from the body, the pool of cholesterol in the body will also be reduced, and arteriosclerosis caused by the above mechanism will be prevented. Therefore,
Although it is expected to have not only the effect of lowering serum cholesterol levels, but also the effect of lowering liver cholesterol levels and the effect of promoting bile acid excretion, to date, there has been no known substance that exhibits these three effects alone.
特開昭59−80610号公報にはストレプトコツカス
属微生物の蛋白分解酵素処理物から分子量約3500以
下の成分を除いて得られる両分がコレステロール低下活
性を有することが、また特開昭61−109729号公
報にはビフィドバクテリウム属またはラクトバチルス属
に属する微生物の菌体がコレステロール低下作用を有す
ることが、さらに特開昭62−258323号公報には
ラクトバチルス属もしくはビフィドバクテリウム属に属
する微生物が血清コレステロール上昇抑制作用を有する
ことが、それぞれ記載されているが、それ以上に脂質代
謝改善に有効な作用を示すことは記載されていない。JP-A-59-80610 discloses that a substance obtained by removing components with a molecular weight of about 3,500 or less from a proteolytic enzyme-treated product of a microorganism of the genus Streptococcus has cholesterol-lowering activity, and JP-A-61-80610 discloses that a substance obtained by removing components with a molecular weight of about 3,500 or less has cholesterol-lowering activity. No. 109729 discloses that microorganisms belonging to the genus Bifidobacterium or Lactobacillus have a cholesterol-lowering effect, and JP-A-62-258323 discloses that microorganisms belonging to the genus Bifidobacterium or Bifidobacterium have a cholesterol-lowering effect. Although it has been described that the microorganisms to which they belong have an effect of suppressing the increase in serum cholesterol, there is no description that they have any more effective effect on improving lipid metabolism.
本発明の目的は、上記問題点に鑑み、高脂肪食摂取にと
もなう血清脂質および肝臓脂質の上昇を抑制し、且つ糞
便へのステロールの排泄を促進するなど、食事性高コレ
ステロール血症を総合的に予防するのに有効な、かつ長
期間摂取しても安全な、脂質代謝改善剤を提供すること
にある。In view of the above-mentioned problems, the purpose of the present invention is to comprehensively treat dietary hypercholesterolemia by suppressing the increase in serum lipids and liver lipids associated with high-fat food intake, and promoting the excretion of sterols into feces. The object of the present invention is to provide a lipid metabolism improving agent that is effective in preventing the effects of cancer and is safe even when ingested for a long period of time.
上記目的を達成することに成功した本発明は、乳酸桿菌
の熱水抽出残渣または該熱水抽出残渣をさらに蛋白分解
酵素で処理したものを有効成分とする、肝臓脂質上昇抑
制、糞便へのステロール排泄促進などの作用を併せ持つ
脂質代謝改善剤を提供するものである。The present invention, which has succeeded in achieving the above objects, uses as an active ingredient a hot water extraction residue of Lactobacillus or a product obtained by further treating the hot water extraction residue with a proteolytic enzyme. The present invention provides a lipid metabolism improving agent that also has effects such as promoting excretion.
本発明の脂質代謝改善剤の製造法をまず説明するIと、
乳酸桿菌としてはラクトバチルス属に属するものが適当
であり、中でも好ましいのは、ラクトバチルス・カゼイ
である。好ましい具体例としては、ラクトバチルス・カ
ゼイYI79018株(微工研菌寄第665号)がある
。I will first explain the method for producing the lipid metabolism improving agent of the present invention;
As the lactic acid bacterium, those belonging to the genus Lactobacillus are suitable, and among them, Lactobacillus casei is preferred. A preferred specific example is Lactobacillus casei strain YI79018 (Feikoken Bacterium No. 665).
本発明の脂質代謝改善剤に用いる乳酸桿菌は任意の培地
で常法により培養されたものでよいが、用途を考慮する
と、グルコース5%、コーンスフ−イーフリカー14%
よりなるコーンステイープリカー培地で培養されたもの
が望ましい。The Lactobacillus used in the lipid metabolism improving agent of the present invention may be cultured in any medium by a conventional method, but considering the use, 5% glucose and 14% corn syrup
It is preferable to use a cornstap liquor culture medium consisting of:
培地から常法により菌体を採取し、洗浄する。続いて、
菌体を20〜80g/lの濃度で水に懸濁させ、50−
70°Oで1−5時間静置したのち100−121℃に
10〜30分間保持すればよいが、50〜70’0で静
置する工程は省略することもできる。Bacterial cells are collected from the culture medium using a conventional method and washed. continue,
The bacterial cells were suspended in water at a concentration of 20 to 80 g/l, and
After being allowed to stand at 70°O for 1-5 hours, it may be held at 100-121°C for 10-30 minutes, but the step of leaving it at 50-70'O can be omitted.
処理後、遠心分離など菌体分離の常法により抽出残渣を
採取し、凍結乾燥する。乾燥物は、そのまま本発明の第
一の脂質代謝改善剤として使用することができる。After the treatment, the extraction residue is collected by a conventional method for bacterial cell separation such as centrifugation and freeze-dried. The dried product can be used as it is as the first lipid metabolism improving agent of the present invention.
これをさらに蛋白分解酵素で処理して使用する場合は、
アクチナーゼ、トリプシン等、菌体蛋白を分解できる蛋
白分解酵素を用いて菌体蛋白の大部分が加水分解される
まで適当時間処理し、その後、分子量で分画して蛋白加
水分解物を除く。分画は分子量的50.000以下の蛋
白分解物含有画分を除くことのできる限外濾過、透析、
分子篩等の手段で行う。有効成分が存在する高分子量画
分は、減圧下に濃縮したのち凍結乾燥して、本発明の第
二の脂質代謝改善剤に用いる。If this is further treated with proteolytic enzymes,
The cells are treated with a proteolytic enzyme capable of decomposing cell proteins, such as actinase or trypsin, for an appropriate period of time until most of the cell proteins are hydrolyzed, and then fractionated based on molecular weight to remove protein hydrolysates. Fractionation is carried out by ultrafiltration, dialysis, which can remove fractions containing protein decomposition products with a molecular weight of 50,000 or less.
This is carried out using means such as molecular sieves. The high molecular weight fraction containing the active ingredient is concentrated under reduced pressure and then lyophilized for use in the second lipid metabolism improving agent of the present invention.
本発明による脂質代謝改善剤は、血清コレステロール値
の上昇を抑制するだけでなく肝臓脂質の上昇を抑制し、
且つ糞便へのステロールの排泄を促進するから、動脈硬
化等、コレステロール蓄積が原因の疾患の予防にきわめ
て有効なものである。蛋白分解酵素処理物はこれらの作
用が特に優れている。The lipid metabolism improving agent according to the present invention not only suppresses the rise in serum cholesterol levels but also suppresses the rise in liver lipids,
In addition, since it promotes the excretion of sterol into feces, it is extremely effective in preventing diseases caused by cholesterol accumulation, such as arteriosclerosis. Proteolytic enzyme-treated products are particularly excellent in these effects.
本発明の脂質代謝改善剤は、そのまま、あるいは医薬品
製造に通常使用される賦形剤その他の助剤と混合して経
口投与することができる。はとんど無味無臭のものであ
るから、任意の飲食品に配合して日常的に投与すること
もできる。The lipid metabolism improving agent of the present invention can be orally administered as it is or mixed with excipients and other auxiliary agents commonly used in pharmaceutical manufacturing. Since it is mostly tasteless and odorless, it can be added to any food or drink and administered on a daily basis.
製造実施例1
ラクトバチルス・カゼイ YIT9018をコーンステ
イープリカー培地400aに接種し、35°Cで2時間
、培地pHを6.0に制御しながら培養した。その後、
遠心分離により菌体を集めて洗浄し、乾燥菌体として2
.4kgの菌体を得た。Production Example 1 Lactobacillus casei YIT9018 was inoculated into corn staple liquor medium 400a and cultured at 35°C for 2 hours while controlling the medium pH to 6.0. after that,
The bacterial cells were collected by centrifugation, washed, and dried as 2
.. 4 kg of bacterial cells were obtained.
この菌体を481iの水に懸濁させ、55°Cで2時間
、pHを7に制御しながら放置した。次いで100°C
に10分間加熱し、可溶性成分を溶出させた。遠心分離
により可溶性画分を除去し、菌体熱水抽出残渣(以下、
製剤Aという)1.5kg(乾燥重量)を得た。The bacterial cells were suspended in 481i water and left at 55°C for 2 hours while controlling the pH to 7. Then 100°C
The mixture was heated for 10 minutes to elute soluble components. The soluble fraction was removed by centrifugation, and the bacterial cell hot water extraction residue (hereinafter referred to as
1.5 kg (dry weight) of formulation A) was obtained.
製造実施例2
製造実施例1で得られた菌体熱水抽出残渣300gを1
/15M・リン酸緩衝液(pH11,6)3Qに懸濁さ
せ、高圧ホモシネ−ターにより均質化したのち、蛋白分
解酵素・アクチナーゼ(科研製薬株式会社)12gを添
加し、50°Cで16時間反応させた。なお、反応中の
腐敗防止のため、防腐剤としてトルエンを添加した。Production Example 2 300 g of the bacterial cell hot water extraction residue obtained in Production Example 1 was
/15M phosphate buffer (pH 11,6) 3Q and homogenized using a high-pressure homogenizer, then 12g of protease actinase (Kaken Pharmaceutical Co., Ltd.) was added and the mixture was heated at 50°C for 16 hours. Made it react. Note that toluene was added as a preservative to prevent spoilage during the reaction.
反応終了後、限外濾過により分子量5万以下の画分を除
いてから凍結乾燥し、乾燥物(以下、製剤Bという)1
00gを得た。After the reaction is completed, fractions with a molecular weight of 50,000 or less are removed by ultrafiltration, and then freeze-dried to obtain a dried product (hereinafter referred to as Formulation B) 1.
00g was obtained.
試験例1
4週齢の雄SDラットを1群6匹の3群に分け、各群に
それぞれ表1に示した飼料を自由に摂取させ、2週間飼
育した。なお、すべてのラットはあらかじめ対照区用の
標準食で1週間飼育しておいた。Test Example 1 Four-week-old male SD rats were divided into three groups of six animals per group, and each group was allowed to freely consume the feed shown in Table 1, and kept for two weeks. Note that all rats were previously fed with a standard diet for a control group for one week.
表1
対照群■ 対照群■ 試験群
飼料成分 (標準食)(高脂肪食)(製剤A添加食)
カゼイン 20 20 20ラー
ド 99
大豆油 1011
ミネラル混合物 4 4 4ビタミン混
合物 1 1 1塩化コリン
0.15 0.15 0.15コレステロール
−0,50,5
コール酸Na O,1250,12
5濾紙粉末 5 5 1製剤A4
ショ糖 59.85 59.225 5
9.225合計 100 100
1oO(注)ミネラル混合物、ビタミン混合物:ハ
ーバ−の混合物
群分は後2週間の飼料摂取量は、対照群■で235±1
8g1対照群■で233±22g1試験群で247±2
5gであり、各群間に差はなかった。その後、18時間
絶食させたのち麻酔下で腹部大動脈より採血した。採血
後、生理食塩水を潅流しながら肝臓を摘出し、直ちに氷
冷してから重量測定後、凍結保存した。Table 1 Control group ■ Control group ■ Test group feed ingredients (standard diet) (high-fat diet) (formulation A additive diet)
Casein 20 20 20 Lard 99 Soybean oil 1011 Mineral mixture 4 4 4 Vitamin mixture 1 1 1 Choline chloride
0.15 0.15 0.15 Cholesterol -0,50,5 Na Cholate O,1250,12
5 Filter paper powder 5 5 1 Formulation A4 Sucrose 59.85 59.225 5
9.225 total 100 100
1oO (Note) Mineral mixture, vitamin mixture: For the Herb mixture group, the feed intake for the next two weeks was 235 ± 1 for the control group.
8g1 control group■ 233±22g1 test group 247±2
5g, and there was no difference between the groups. Thereafter, after fasting for 18 hours, blood was collected from the abdominal aorta under anesthesia. After blood collection, the liver was removed while being perfused with physiological saline, immediately cooled on ice, weighed, and stored frozen.
また、絶食前、2日間、糞便を採取した。In addition, feces were collected for 2 days before fasting.
採取した血液は、遠心分離して血清を集め、血清脂質を
分析した。肝臓は、乾燥試料をクロロホルム−メタノー
ル混液(2: 1)で抽出し、肝臓脂質を分析した。糞
便は、乾燥後、熱エタノールで抽出し、抽出液について
分析した。The collected blood was centrifuged to collect serum, and serum lipids were analyzed. A dried liver sample was extracted with a chloroform-methanol mixture (2:1), and liver lipids were analyzed. After drying, the feces were extracted with hot ethanol and the extract was analyzed.
分析結果は表2〜表4に示したとおりであって、コレス
テロールを添加した高脂肪食を与えることにより対照群
■では総コレステロールL VLDL十LDLコレステ
ロール値、および動脈硬化指数が上昇したが、同じ高脂
肪食でも製剤Aを添加した試験群では上記分析項目のす
べてにおいて数値上昇が顕著に抑制された。また、血清
トリグリセリドの値も、試験群で低下する傾向が認めら
れた。The analysis results are as shown in Tables 2 to 4, and in the control group ■, total cholesterol levels and arteriosclerotic index increased by feeding a high-fat diet supplemented with cholesterol; Even on a high-fat diet, in the test group to which Formulation A was added, increases in numerical values in all of the above analytical items were significantly suppressed. Furthermore, serum triglyceride values also tended to decrease in the test group.
表2 血清脂質
注:数値は平均値上標準偏差。a−b問およびc−d間
に危険率5%で有意差あり(以下の各表においても同じ
)。Table 2 Serum lipids Note: Values are standard deviation above the mean. There is a significant difference between questions a and b and c and d at a risk rate of 5% (the same applies to each table below).
表3 肝臓脂質
表4 糞便脂質
試験例2
4週齢の雄SDラット1群8匹を用いて、試験例1と同
様の試験を行なった。ただし、試験群の飼料に配合する
脂質代謝改善剤としては製剤Aに替えて製造実施例2に
よる製剤Bを用いた。Table 3 Liver Lipid Table 4 Fecal Lipid Test Example 2 A test similar to Test Example 1 was conducted using 1 group of 8 4-week-old male SD rats. However, Formulation B according to Production Example 2 was used instead of Formulation A as the lipid metabolism improving agent added to the feed of the test group.
群分は後の2週間の飼料摂取量は、標準食の対照群■で
232±24g1高脂肪食の対照群■では229±22
g1試験群で239±16gであり、各群間に差はなか
った。The feed intake for the next two weeks was 232 ± 24 g for the standard diet control group (■) and 229 ± 22 g for the high-fat diet control group (■).
It was 239±16 g in the g1 test group, and there was no difference between each group.
血清脂質、肝臓脂質および糞便脂質の分析結果は表5〜
7に示したとおりであって、コレステロールを添加した
高脂肪食を与えることにより対照群■では総コレステロ
ール値、VLDL+LDLコレステロール値、および動
脈硬化指数が上昇したが、同じ高脂肪食でも製剤Bを添
加した試験群では上記分析項目のすべてにおいて上昇が
顕著に抑制された。ま°た、血清トリグリセリドの値も
、試験群では僅、かながら低下する傾向が認められた。Analysis results of serum lipids, liver lipids, and fecal lipids are shown in Table 5.
As shown in 7, the total cholesterol level, VLDL + LDL cholesterol level, and arteriosclerotic index increased in the control group ■ by feeding a high-fat diet with added cholesterol, but even with the same high-fat diet, formulation B increased. In the test group, increases in all of the above analysis items were significantly suppressed. Furthermore, serum triglyceride values also tended to slightly decrease in the test group.
表5 血清脂質
表6 肝臓脂質
表7 糞便脂質
〔発明の効果〕
上述のように、乳酸桿菌の熱水抽出物またはその蛋白分
解酵素処理物からなる本発明の脂質代謝改善剤は顕著な
血清脂質上昇抑制作用、肝臓脂質上昇抑制作用ならびに
コレステロールおよび胆汁酸の糞便への排泄を促進する
作用を示し、動脈硬化その他コレステロール蓄積が原因
の疾患の予防に極めて有効なものである。Table 5 Serum Lipids Table 6 Liver Lipids Table 7 Fecal Lipids [Effects of the Invention] As mentioned above, the lipid metabolism improving agent of the present invention, which is composed of a hot water extract of Lactobacillus or a protease-treated product thereof, significantly improves serum lipids. It exhibits an effect of suppressing the rise in cholesterol levels, an effect of suppressing the rise of liver lipids, and an effect of promoting the excretion of cholesterol and bile acids into the feces, and is extremely effective in preventing arteriosclerosis and other diseases caused by cholesterol accumulation.
しかも、乳酸桿菌は古くから乳酸発酵食品の製造に利用
されていることから明らかなように病原性のない安全な
細菌であり、その処理物からなる本発明の脂質代謝改善
剤も、ラットに経口投与した場合8 g/kgの投与量
でも死亡例は認められず、長期間投与しても安全性には
問題がない。Moreover, Lactobacillus is a non-pathogenic and safe bacterium, as is clear from the fact that it has been used for a long time in the production of lactic acid fermented foods. No deaths were observed even at a dose of 8 g/kg, and there is no safety problem even when administered for a long period of time.
したがって、本発明の脂質代謝改善剤は経口投与する医
薬として利用するほか、食品に混合して日常的に摂取さ
せ動脈硬化予防と健康増進に役立たせるのにも適したき
わめて有利なものである。Therefore, the lipid metabolism improving agent of the present invention is extremely advantageous, as it is suitable for use as an orally administered medicine, and also for daily intake by mixing with food to help prevent arteriosclerosis and promote health.
Claims (3)
謝改善剤。(1) A lipid metabolism improving agent containing a hot water extraction residue of Lactobacillus as an active ingredient.
成分とする脂質代謝改善剤。(2) A lipid metabolism improving agent containing a lactic acid bacterium hot water extraction residue treated with a proteolytic enzyme as an active ingredient.
1または2に記載の脂質代謝改善剤。(3) The lipid metabolism improving agent according to claim 1 or 2, wherein the lactic acid bacterium is Lactobacillus casei.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2330533A JP2855290B2 (en) | 1990-11-30 | 1990-11-30 | Lipid metabolism improver |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2330533A JP2855290B2 (en) | 1990-11-30 | 1990-11-30 | Lipid metabolism improver |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH04208226A true JPH04208226A (en) | 1992-07-29 |
JP2855290B2 JP2855290B2 (en) | 1999-02-10 |
Family
ID=18233700
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Application Number | Title | Priority Date | Filing Date |
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JP2330533A Expired - Fee Related JP2855290B2 (en) | 1990-11-30 | 1990-11-30 | Lipid metabolism improver |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0792586A3 (en) * | 1996-02-28 | 1999-04-07 | Unilever N.V. | Food products containing bacteria with cholesterol lowering activity |
JP2001512747A (en) * | 1997-08-05 | 2001-08-28 | プロビ エービー | Use of Lactobacillus to reduce fibrinogen levels in blood |
-
1990
- 1990-11-30 JP JP2330533A patent/JP2855290B2/en not_active Expired - Fee Related
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0792586A3 (en) * | 1996-02-28 | 1999-04-07 | Unilever N.V. | Food products containing bacteria with cholesterol lowering activity |
JP2001512747A (en) * | 1997-08-05 | 2001-08-28 | プロビ エービー | Use of Lactobacillus to reduce fibrinogen levels in blood |
JP4651814B2 (en) * | 1997-08-05 | 2011-03-16 | プロビ エービー | Use of Lactobacillus to reduce blood fibrinogen levels |
Also Published As
Publication number | Publication date |
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JP2855290B2 (en) | 1999-02-10 |
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