JP2855290B2 - Lipid metabolism improver - Google Patents
Lipid metabolism improverInfo
- Publication number
- JP2855290B2 JP2855290B2 JP2330533A JP33053390A JP2855290B2 JP 2855290 B2 JP2855290 B2 JP 2855290B2 JP 2330533 A JP2330533 A JP 2330533A JP 33053390 A JP33053390 A JP 33053390A JP 2855290 B2 JP2855290 B2 JP 2855290B2
- Authority
- JP
- Japan
- Prior art keywords
- lipid metabolism
- cholesterol
- serum
- improving agent
- present
- 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.)
- Expired - Fee Related
Links
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)
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。Description: TECHNICAL FIELD The present invention relates to a lipid metabolism-improving agent having a serum lipid elevation inhibitory action, a liver lipid elevation inhibitory action, a sterol excretion promoting action, 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、成人死亡原因の第一位を占めている。In recent years, mortality from cardiovascular disease has been increasing year by year,
Combined with diseases caused by arteriosclerosis such as myocardial infarction and cerebral infarction, they are the leading cause of adult death.
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, elevated serum lipids, especially serum cholesterol, are regarded as 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、肝毒
性、胃腸障害、発癌性等の副作用がある。Genetic disorders are the primary cause of elevated serum cholesterol. In this case, drugs such as cholesterol synthesis inhibitors, nicomol, clofibrate, ion-exchange resins, and anabolic steroids are used for severely ill patients at the same time as dietary therapy. 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、若年令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、脂肪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 the overdose of fat due to recent changes in dietary habits, which is becoming more pronounced among younger people. Dietary hypercholesterolemia usually does not lead to severe hypercholesterolemia, but the problem is that cholesterol gradually accumulates in blood vessels from a young age and causes arteriosclerosis in adults. Yes, there is a risk of myocardial or cerebral infarction in combination with hypertriglyceridemia. For this type of hyperlipidemia, dietary treatment in which fat intake is restricted to an appropriate range is more important than drug therapy which has problems such as side effects. However, dietary restriction is accompanied by emotional distress and enjoys eating habits, so it is difficult to implement it strictly and its effect 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、糞便とともに対
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だけでなく肝臓コ
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。Excess cholesterol in serum accumulates in the blood vessel wall and causes arteriosclerosis, but after it is taken up by the liver, it is converted to bile acids without accumulating there and released into the intestinal tract as it is If it is excreted with feces outside the body, the pool of cholesterol in the body is also reduced, and arteriosclerosis by the above mechanism is prevented. Therefore, it is expected to have not only a serum cholesterol level lowering action but also a liver cholesterol level lowering action and a bile acid excretion promoting action, but conventionally, none of them showing such three actions alone is known. .
特開昭59−80610号公報にはストレプトコッカス属微
生物の蛋白分解酵素処理物から分子量約3500以下の成分
を除いて得られる画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ルチ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 fraction obtained by removing a component having a molecular weight of about 3500 or less from a protease-treated product of a Streptococcus microorganism has cholesterol-lowering activity. The publication states that the cells of a microorganism belonging to the genus Bifidobacterium or Lactobacillus have a cholesterol-lowering effect. Each of them is described to have a serum cholesterol elevation inhibitory effect, but it is not described that it exhibits an effect more effective for 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
長時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 problems, an object of the present invention is to comprehensively reduce dietary hypercholesterolemia, such as suppressing the elevation of serum lipids and hepatic lipids accompanying high-fat diet intake and promoting excretion of sterols into feces. It is an object of the present invention to provide a lipid metabolism improving agent which is effective for prevention of inflammation and is safe even if taken for a long time.
上記目的を達成することを成功した本発明は、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。但しこの発明
における「熱水抽出残渣」とは、菌体を水に懸濁させて
50〜70℃で1〜5時間静置する前処理を伴う熱水抽出を
施して得られた抽出残渣を意味する。The present invention, which has successfully achieved the above object, provides a lactic acid bacterium hot water extraction residue or a substance obtained by treating the hot water extraction residue with a protease further as an active ingredient, suppressing hepatic lipid elevation and sterols in feces. An object of the present invention is to provide a lipid metabolism-improving agent having an effect of promoting excretion and the like. However, the “residue of hot water extraction” in the present invention means that the cells are suspended in water.
It means an extraction residue obtained by performing hot water extraction accompanied by pretreatment left at 50 to 70 ° C for 1 to 5 hours.
本発明の脂質代謝改善剤の製造法をまず説明すると、
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・カゼ
イYIT9018株(微工研菌寄第665号)がある。First, the method for producing the lipid metabolism improving agent of the present invention will be described.
Lactobacillus belonging to the genus Lactobacillus is suitable, and Lactobacillus casei is particularly preferred. A preferred specific example is Lactobacillus casei YIT9018 strain (Microtechnical Laboratory 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%、コーンスティープリカー14%よ
りなるコーンスティープリカー培地で培養されたものが
望ましい。The lactobacilli used in the lipid metabolism improving agent of the present invention may be those cultured by an ordinary method in an arbitrary medium. However, in consideration of the use, they are cultured in a corn steep liquor medium consisting of glucose 5% and corn steep liquor 14%. Is desirable.
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/の濃度で水に懸濁させ、50〜70℃
で1〜5時間静置したのち100〜121℃に10〜30分間保持
する。The cells are collected from the medium by a conventional method and washed. Subsequently, the cells were suspended in water at a concentration of 20-80 g / 50-70 ° C.
And then kept at 100-121 ° C for 10-30 minutes.
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 of 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。分画は分子量約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。When this is further treated with a protease, it is treated with an actinase, trypsin or other protease capable of degrading the bacterial protein for an appropriate time until most of the bacterial protein is hydrolyzed, and then And fractionation by molecular weight to remove protein hydrolysates. The fractionation is performed by means of ultrafiltration, dialysis, molecular sieve, or the like which can remove a fraction containing a protein hydrolyzate having a molecular weight of about 50,000 or less. The high molecular weight fraction in which the active ingredient is present is concentrated under reduced pressure, lyophilized, and used as 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環状脂質の上昇を抑制
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 a rise in serum cholesterol level but also suppresses a rise in cyclic lipids and promotes the excretion of sterols into feces. It is extremely effective in preventing illness. Protease 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。ほ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 auxiliaries usually used for the production of pharmaceuticals. Since it is almost tasteless and odorless, it can be administered daily by blending it with any food or drink.
製造実施例1 ラクトバチルス・ガセイYIT9018をコーンスティープ
リカー培地400に接種し、35℃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 gasei YIT9018 was inoculated into corn steep liquor medium 400, and the medium pH was increased to 6.0 at 35 ° C. for 2 hours.
While culturing. Thereafter, the cells were collected and washed by centrifugation to obtain 2.4 kg of dried cells.
この菌体を48の水に懸濁させ、55℃で2時間、pHを
7に制御しながら放置した。次いで100℃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 cells were suspended in 48 water and left at 55 ° C. for 2 hours while controlling the pH at 7. Then, the mixture was heated to 100 ° C. for 10 minutes to elute the soluble components. The soluble fraction is removed by centrifugation, and the bacterial cell hot water extraction residue (hereinafter referred to as formulation A)
1.5 kg (dry weight) were 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1/15
M・リン酸緩衝液(pH8.6)3に懸濁させ、高圧ホモジ
ネー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℃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 hot water extraction residue obtained from Production Example 1 was 1/15
After suspending in M · phosphate buffer (pH 8.6) 3 and homogenizing with a high-pressure homogenator, 12 g of protease / actinase (Kaken Pharmaceutical Co., Ltd.) was added and reacted at 50 ° C. for 16 hours. To prevent decay during the reaction, toluene was added as a preservative.
反応終了後、限外濾過により分子量5万以下の画分を
除いてから連結乾燥し、乾燥物(以下、製剤Bという)
100gを得た。After the completion of the reaction, the fraction having a molecular weight of 50,000 or less is removed by ultrafiltration, and then linked and dried.
100 g were 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 rats, and each group was allowed to freely take the feed shown in Table 1 and bred for 2 weeks. In addition, all the rats were bred in advance on a standard diet for control for one week.
群分け後2週間の飼料摂取量は、対照群で235±18
g、対照群で233±22g、試験群で247±25g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
酔下で腹部大静脈より採血した。採血後、生理食塩水を
灌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。また、絶食前、2日間、糞便を採
取した。 The feed intake for 2 weeks after grouping was 235 ± 18 in the control group.
g, 233 ± 22 g in the control group and 247 ± 25 g in the test group, and there was no difference between the groups. Then, after fasting for 18 hours, blood was collected from the abdominal vena cava under anesthesia. After blood collection, the liver was excised while perfusing physiological saline, immediately cooled on ice, weighed, and then frozen and stored. In addition, feces were collected for two 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 analyzed for serum lipids. For the liver, the dried sample was extracted with a chloroform-methanol mixture (2: 1), and the liver lipid was analyzed. The stool was dried, extracted with hot ethanol, and analyzed for the extract.
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 shown in Tables 2 to 4. The total fat cholesterol, VLDL + LDL cholesterol, and atherosclerosis index were increased in the control group by feeding a high fat diet to which cholesterol was added. In the test group to which Formulation A was added also in the diet, the numerical increase was significantly suppressed in all of the above analysis items. In addition, serum triglyceride levels also tended to decrease in the test group.
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。 Test Example 2 The same test as in Test Example 1 was carried out using eight 4-week-old male SD rats per group. However, as the lipid metabolism improving agent to be mixed with the feed of the test group, the formulation A according to Production Example 2 was used instead of the formulation A.
群分け後の2週間の飼料摂取量は、標準食の対照群
で232±24g、高脂肪食の対照群では229±22g、試験群
で239±16gであり、各群間に差はなかった。The feed intake for 2 weeks after grouping was 232 ± 24 g in the standard diet control group, 229 ± 22 g in the high fat diet control group, and 239 ± 16 g in the 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。Table 5 shows the results of analysis of serum lipids, liver lipids and fecal lipids.
7, the total fat cholesterol level, the VLDL + LDL cholesterol level and the atherosclerosis index increased in the control group when the high fat diet supplemented with cholesterol was added. In the test group, the increase was significantly suppressed in all of the above analysis items. In addition, the serum triglyceride level also tended to slightly decrease in the test group.
〔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。 [Effects of the Invention] As described above, the lipid metabolism-improving agent of the present invention comprising a hot-water extract of lactobacilli or a proteolytic enzyme-treated product thereof has a remarkable inhibitory effect on serum lipid elevation, hepatic lipid elevation inhibition, cholesterol and It has the effect of promoting the excretion of bile acids into 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8g/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, lactobacilli are safe bacteria without pathogenicity, as is clear from the fact that they have been used for the production of lactic acid-fermented foods for a long time. No mortality was observed even at a dose of 8 g / kg when administered, and there is no problem in safety even if administered for a long 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, which is suitable not only for use as a medicament for oral administration, but also for admixing it with food and ingesting it daily to help prevent arteriosclerosis and promote health.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭61−109729(JP,A) 特開 昭62−258323(JP,A) (58)調査した分野(Int.Cl.6,DB名) A61K 35/74 A23L 1/30,1/305 A61K 38/01,38/02────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-61-109729 (JP, A) JP-A-62-258323 (JP, A) (58) Fields investigated (Int. Cl. 6 , DB name) A61K 35/74 A23L 1 / 30,1 / 305 A61K 38 / 01,38 / 02
Claims (3)
脂質代謝改善剤。1. An agent for improving lipid metabolism comprising a hot water extraction residue of lactobacilli as an active ingredient.
を有効成分とする脂質代謝改善剤。2. A lipid metabolism-improving agent comprising, as an active ingredient, a processed product of a lactobacilli hot water extraction residue proteolytic enzyme.
請求項1または2に記載の脂質代謝改善剤。3. The method according to claim 1, wherein the lactobacillus 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 JPH04208226A (en) | 1992-07-29 |
JP2855290B2 true JP2855290B2 (en) | 1999-02-10 |
Family
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Family Applications (1)
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 |
Country Status (1)
Country | Link |
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JP (1) | JP2855290B2 (en) |
Families Citing this family (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 |
SE510753C2 (en) * | 1997-08-05 | 1999-06-21 | Probi Ab | Use of a strain of Lactobacillus for the manufacture of a drug for reducing fibrinogen content in blood |
-
1990
- 1990-11-30 JP JP2330533A patent/JP2855290B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
JPH04208226A (en) | 1992-07-29 |
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