JPH04327536A - Method for treating and preventing hyperlipidemia and obesity - Google Patents
Method for treating and preventing hyperlipidemia and obesityInfo
- Publication number
- JPH04327536A JPH04327536A JP3121892A JP12189291A JPH04327536A JP H04327536 A JPH04327536 A JP H04327536A JP 3121892 A JP3121892 A JP 3121892A JP 12189291 A JP12189291 A JP 12189291A JP H04327536 A JPH04327536 A JP H04327536A
- Authority
- JP
- Japan
- Prior art keywords
- treating
- cholesterol
- lipids
- obesity
- absorption
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 10
- 208000008589 Obesity Diseases 0.000 title claims abstract description 5
- 235000020824 obesity Nutrition 0.000 title claims abstract description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 title abstract description 4
- 150000002632 lipids Chemical class 0.000 claims abstract description 16
- 238000010521 absorption reaction Methods 0.000 claims abstract description 7
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- 235000013305 food Nutrition 0.000 claims abstract description 6
- 230000029087 digestion Effects 0.000 claims abstract description 5
- 239000003112 inhibitor Substances 0.000 claims abstract description 5
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 6
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 3
- 102100031416 Gastric triacylglycerol lipase Human genes 0.000 claims 1
- 108050006759 Pancreatic lipases Proteins 0.000 claims 1
- 102000019280 Pancreatic lipases Human genes 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 108010091264 gastric triacylglycerol lipase Proteins 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 229940116369 pancreatic lipase Drugs 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 102000004882 Lipase Human genes 0.000 abstract description 5
- 108090001060 Lipase Proteins 0.000 abstract description 5
- 239000004367 Lipase Substances 0.000 abstract description 5
- 235000019421 lipase Nutrition 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 244000068988 Glycine max Species 0.000 abstract description 2
- 235000010469 Glycine max Nutrition 0.000 abstract description 2
- 241000282414 Homo sapiens Species 0.000 abstract description 2
- 230000001079 digestive effect Effects 0.000 abstract description 2
- 210000001819 pancreatic juice Anatomy 0.000 abstract description 2
- 230000000881 depressing effect Effects 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 abstract 1
- 210000004051 gastric juice Anatomy 0.000 abstract 1
- 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 description 19
- 210000002966 serum Anatomy 0.000 description 12
- 238000002835 absorbance Methods 0.000 description 9
- 235000012000 cholesterol Nutrition 0.000 description 9
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 108010023302 HDL Cholesterol Proteins 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 229940127470 Lipase Inhibitors Drugs 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000004040 coloring Methods 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229940127328 Cholesterol Synthesis Inhibitors Drugs 0.000 description 2
- 108010089254 Cholesterol oxidase Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229920002494 Zein Polymers 0.000 description 2
- 108010055615 Zein Proteins 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 235000006694 eating habits Nutrition 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005019 zein Substances 0.000 description 2
- 229940093612 zein Drugs 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000186321 Cellulomonas Species 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 102100022119 Lipoprotein lipase Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 102000000019 Sterol Esterase Human genes 0.000 description 1
- 108010055297 Sterol Esterase Proteins 0.000 description 1
- 241000520730 Streptomyces cinnamoneus Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
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- 235000021307 Triticum Nutrition 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000008687 biosynthesis inhibition Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 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
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- MWEQTWJABOLLOS-AZGWGOJFSA-L disodium;[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O MWEQTWJABOLLOS-AZGWGOJFSA-L 0.000 description 1
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- 235000019634 flavors Nutrition 0.000 description 1
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- 235000012041 food component Nutrition 0.000 description 1
- 239000005428 food component Substances 0.000 description 1
- 108010054790 glycerol-3-phosphate oxidase Proteins 0.000 description 1
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- 229920000669 heparin Polymers 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
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- 229930014626 natural product Natural products 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
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- 239000012266 salt solution Substances 0.000 description 1
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【０００１】0001
【産業上の利用分野】この発明は食物由来の脂質の消化
・吸収を抑制又は阻害することにより、高脂血症や肥満
を治療し、予防する方法に関する。FIELD OF THE INVENTION This invention relates to a method for treating and preventing hyperlipidemia and obesity by suppressing or inhibiting the digestion and absorption of food-derived lipids.
【０００２】0002
【従来の技術】生体中の脂質は食事から吸収されるもの
と、体内で生合成されるものとがあり、食事中のほとん
どの成分が程度の差こそあれ血清脂質に影響を与えてい
る。なかでも、脂質は最も影響力の大きい食品成分であ
る。近年わが国においても、食生活及びその形態のアメ
リカ化（全摂取エネルギに占める脂質エネルギ比約４０
％に近づきつつある）に伴ない、高コレステロ−ル血症
や高トリグリセライド血症による虚血性心疾患、虚血性
脳疾患発症の頻度が非常に増加している。これらによる
死亡率はアメリカでは癌によるそれをはるかに凌いでお
り、わが国においても癌に次いで多く、食生活を含めた
ライフスタイルのアメリカ化の進展や、人口の高齢化等
の要因により、今後さらに増加すると予想されている。BACKGROUND OF THE INVENTION There are two types of lipids in living organisms: those that are absorbed from meals and those that are biosynthesized within the body, and most of the components in meals affect serum lipids to varying degrees. Among them, lipids are the most influential food components. In recent years, even in Japan, there has been an Americanization of dietary habits and their forms (the ratio of fat energy to total energy intake is about 40%).
%), the frequency of ischemic heart disease and ischemic brain disease due to hypercholesterolemia and hypertriglyceridemia is greatly increasing. The mortality rate from these diseases far exceeds that from cancer in the United States, and is second only to cancer in Japan, and will continue to rise in the future due to factors such as the progress of Americanization of lifestyles, including dietary habits, and the aging of the population. is expected to increase.
【０００３】これらの主要因である高脂血症を治療又は
予防するには、脂質の摂取制限を主とした食事療法が非
常に有効であるが、極めて長期間に亘る食事療法は食生
活の急変を招く。なおかつ脂質は多くの食品のテクスチ
ヤ−、フレ−バアロマ等に深く関与しており、嗜好の面
で欠くことができないものであり、ほとんどの例で厳格
な食事療法や制限が行なわれていないのが現状である。
厳格な食事療法以外に血清脂質を低下させるには、脂質
の吸収阻害、生体内での生合成阻害及び排出促進が考え
られ、それぞれダイエタリフアイバや生体内でのコレス
テロ−ル合成阻害剤の投与などが考案又は実施されてい
る。[0003] To treat or prevent hyperlipidemia, which is the main cause of these problems, dietary therapy that mainly restricts fat intake is very effective, but extremely long-term dietary therapy is Inviting sudden change. Moreover, lipids are deeply involved in the texture, flavor aroma, etc. of many foods, and are indispensable in terms of taste. This is the current situation. In order to lower serum lipids other than strict dietary therapy, inhibition of lipid absorption, inhibition of biosynthesis in the body, and promotion of excretion can be considered, and administration of dietary supplements or cholesterol synthesis inhibitors in the body is recommended, respectively. etc. have been devised or implemented.
【０００４】0004
【発明が解決しようとする課題】ところでダイエタリフ
アイバ投与による血清脂質の低下作用は、未だその機序
が解明されておらず、個体差も著しく、再現性に劣る。
またコレステロ−ル合成阻害剤の使用は加療中の患者に
限られ、一般的な使用は禁じられており、最も問題視さ
れている準高コレステロ−ル血症者や、成人病リスクの
非常に高い肥満者には適用できない。さらにはコレステ
ロ−ルと同等に問題視されているトリグリセライドには
何等影響を及ぼさず、これらに対する積極的な予防法と
は成り得ない。[Problems to be Solved by the Invention] However, the mechanism of the serum lipid lowering effect of dietary fiber administration has not yet been elucidated, there are significant individual differences, and reproducibility is poor. In addition, the use of cholesterol synthesis inhibitors is limited to patients undergoing treatment, and general use is prohibited. Not applicable to highly obese individuals. Furthermore, it has no effect on triglycerides, which are considered to be as problematic as cholesterol, and cannot be used as an active preventive method against them.
【０００５】[0005]
【課題を解決するための手段】そこで発明者らは脂質の
消化、吸収に最も重要に関与している消化液中のリパ−
ゼに着目し、この酵素活性を低下又は阻害させて、胆汁
又は食品中の脂質の吸収を阻害することにより、血中脂
質含有量を低下させると共に、食事による総摂取カロリ
を低下させ、高脂血症や肥満の治療及び予防を行なうこ
とを発案した。そのためリパ−ゼに特異的なインヒビタ
−を天然物に求め、大豆等の豆類や小麦等の穀類種子が
特異的リパ−ゼインヒビタ−を高率に含有していること
を見いだした。[Means for solving the problem] Therefore, the inventors have developed a method to improve the lipid content in the digestive fluid, which is most important in the digestion and absorption of lipids.
By reducing or inhibiting this enzyme activity and inhibiting the absorption of lipids in bile or food, we can lower the blood lipid content and reduce the total calorie intake from meals, reducing high-fat content. He came up with the idea of treating and preventing blood clots and obesity. Therefore, we searched for lipase-specific inhibitors in natural products and found that legumes such as soybeans and grain seeds such as wheat contain a high percentage of specific lipase inhibitors.
【０００６】[0006]
【作用】このリパ−ゼインヒビタ−は、微生物や動物及
びヒト膵液由来リパ−ゼに対して特異的に作用し、他の
酵素類に対しては何等作用しないことを確認した後、動
物及びヒトに経口投与し、血清トリグリセライド、血清
コレステロ−ル及び体重を有意に低下させ得た。[Action] After confirming that this lipase inhibitor acts specifically on lipase derived from microorganisms, animals, and human pancreatic juice, and has no effect on other enzymes, it has been tested in animals and humans. When administered orally, it was able to significantly reduce serum triglycerides, serum cholesterol and body weight.
【０００７】[0007]
方法
動物実験：ＳＤ系ラツト、４週例（♀）を用い、対照群
は高コレステロ−ル食（ＭＦ食にコレステロ−ル１％（
Ｗ／Ｗ）とコ−ル酸２％（Ｗ／Ｗ）を添加）で、リパ−
ゼインヒビタ−投与群は高コレステロ−ル食にリパ−ゼ
インヒビタ−を０．８％（Ｗ／Ｗ）となるように加え、
それぞれ１３日間飼育した。またこの間、飼料の制限は
せず、飼料及び飲料水とともに自由摂取とした。リパ−
ゼインヒビタ−投与開始後４、９及び１３日目に尾動脈
より採血し、３７゜Ｃ、３０分間インキユベ−トし、遠
心分離（３，０００ｒｐｍ、１０ｍｉｎ）により血清を
得た。この血清をトリグリセライド、ＨＤＬ−コレステ
ロ−ル、総コレステロ−ルの測定用に用いた。Methods Animal experiment: SD rats, 4 weeks old (female), were used as a control group on a high-cholesterol diet (MF diet with 1% cholesterol).
(w/w) and 2% (w/w) cholic acid)
For the Zein inhibitor administration group, lipase inhibitor was added to the high cholesterol diet at a concentration of 0.8% (W/W).
Each was reared for 13 days. During this period, feed was not restricted, and the animals were allowed free access to feed and drinking water. Reper
On days 4, 9, and 13 after the start of zein inhibitor administration, blood was collected from the tail artery, incubated at 37°C for 30 minutes, and centrifuged (3,000 rpm, 10 min) to obtain serum. This serum was used for measuring triglyceride, HDL-cholesterol, and total cholesterol.
【０００８】高トリグリセライド血症と、高血圧である
と診断されたボランテイア（４８才、♂、１５８ｃｍ、
６７Ｋｇ）、高コレステロ−ル血症と高血圧であると診
断されたボランテイア（３６才、♂、１７８ｃｍ、７６
Ｋｇ）に通常の食事を摂取させながら、毎夕食事に１０
０ｍｇのリパ−ゼインヒビタ−を経口的に２週間投与し
た。この間３日間毎に上腕静脈から採血し、血清中のト
リグリセライド、総コレステロ−ル、ＨＤＬ−コレステ
ロ−ル量を測定した。また血圧はリパ−ゼインヒビタ−
投与前から投与終了時まで、毎朝起床直後に測定した。[0008] A volunteer (48 years old, male, 158 cm, diagnosed with hypertriglyceridemia and hypertension)
A volunteer (36 years old, male, 178 cm, 76 cm) who was diagnosed with hypercholesterolemia and hypertension (67 kg).
10 Kg) at each dinner meal while feeding the child on a normal diet.
0 mg of lipase inhibitor was administered orally for 2 weeks. During this period, blood was collected from the brachial vein every 3 days, and triglyceride, total cholesterol, and HDL-cholesterol levels in the serum were measured. Blood pressure is also affected by lipase inhibitors.
Measurements were taken every morning immediately after waking up from before administration until the end of administration.
【０００９】血清脂質の測定法：トリグリセライドはト
リグリセライドＥ−テストワコ−（和光純薬）を用いて
測定した。すなわち、血清１０μｌに１．５ｍｌの発色
試薬（５０ｍＭグツド（ＰＩＰＥＳ）緩衝液、ｐＨ６．
５にリポプロテインリパ−ゼ（Ｐｓｅｕｄｏｍｏｎａｓ
属由来）９９ｕｎｉｔｓ／ｍｌ、アデノシン−５’−三
リン酸二ナトリユウム三水和物（ＡＴＰ，Ｂａｃｔｅｒ
ｉｕｍ由来）１．７ｍｍｏｌ、グリセロ−ルキナ−ゼ（
Ｃｅｌｌｕｌｏｍｏｎａｓ属由来）３０ｕｎｉｔｓ／ｍ
ｌ、グリセロ−ル−３−リン酸オキシダ−ゼ（Ｓｔｒｅ
ｐｔｏｃｏｃｃｕｓ属由来）１．０ｕｎｉｔｓ／ｍｌ、
ペルオキシダ−ゼ（西洋ワサビ由来）５．５ｕｎｉｔｓ
／ｍｌ、３．５−ジメトキシ−Ｎ−エチル−Ｎ−（２’
−ヒドロキシ−３’−スルホプロピル）−アニリンナト
リユウム０．５ｎｍｏｌ／ｍｌ、アスコルビン酸オキシ
ダ−ゼ（キユウリ由来）４．５ｕｎｉｔｓ／ｍｌ）を加
え、３７゜Ｃ、５ｍｉｎインキュベ−トし６００ｎｍの
吸光度を測定した。トリグリセライドの濃度（ｍｇ／１
００ｍｌ）は（検体の吸光度／スタンダ−ドの吸光度）
＊３００により算出した。総コレステロ−ル測定には、
ネスコ−トＴＣキツト−Ｋ（日本商事）を用いた。すな
わち、血清１０μｌに呈色試薬（フエノ−ル３３０μｇ
／ｍｌにコレステロ−ルエステラ−ゼ（Ｃｈｒｏｍｏｂ
ａｃｔｅｒｉｕｍ Ｖｉｓｃｏｓｕｍ由来）１５６ｕｎ
ｉｔｓ／ｍｌ、コレステロ−ルオキシダ−ゼ（Ｓｔｒｅ
ｐｔｏｍｙｃｅｓ Ｃｉｎｎａｍｏｎｅｕｓ由来）０．
１５６ｕｎｉｔｓ／ｍｌ、４−アミノアンチピリン０．
１２５ｍｇ／ｍｌ）１．５ｍｌを加え、３７゜Ｃ、１５
ｍｉｎインキユベ−トし、５００ｎｍの吸光度を測定し
た。総コレステロ−ル濃度（ｍｇ／１００ｍｌ）は（検
体の吸光度／標準品の吸光度）×３００で算出した。Ｈ
ＤＬ−コレステロ−ルについてはＨＤＬ−コレステロ−
ル−テストワコ−（和光純薬）を用いて測定した。すな
わち、血清２５μｌに沈殿試薬（ヘパリン、１％メタノ
−ルを含む０．４４％マンガン塩溶液）を１ｍｌ加え、
混合した後、１０分間室温に放置した。
１０，０００ｒｐｍ、１０分間遠心した後、上清０．５
ｍｌに発色試薬（０．１％ｐ−クロロフエノ−ル、トリ
ス（ヒドロキシメチル）アミノメタン、界面活性剤を含
むものにコレステロ−ルエステルヒドロラ−ゼとコレス
テロ−ルオキシダ−ゼを各７５ｍＵ／ｍｌ、ペルオキシ
ダ−ゼと４−アミノアンチピリンを各８４ｎｇ／ｍｌを
含む）を１ｍｌ加え、３７゜Ｃ、１０分間インキユベ−
トした。反応液の５０５ｎｍに対する吸光度を次式に適
用し、ＨＤＬ−コレステロ−ル量（ｍｇ／１００ｍｌ）
を算出した。
ＨＤＬ−コレステロ−ル（ｍｇ／１００ｍｌ）＝（検体
の吸光度／標準品の吸光度）×１００Method for measuring serum lipids: Triglycerides were measured using Triglyceride E-Test Wako (Wako Pure Chemical Industries, Ltd.). That is, 1.5 ml of coloring reagent (50 mM PIPES buffer, pH 6.0) was added to 10 μl of serum.
5, lipoprotein lipase (Pseudomonas
99 units/ml, adenosine-5'-triphosphate disodium trihydrate (ATP, Bacter
ium) 1.7 mmol, glycerolukinase (derived from
(derived from Cellulomonas genus) 30 units/m
l, glycerol-3-phosphate oxidase (Stre
(derived from Ptococcus genus) 1.0 units/ml,
Peroxidase (derived from horseradish) 5.5 units
/ml, 3.5-dimethoxy-N-ethyl-N-(2'
-Hydroxy-3'-sulfopropyl)-aniline sodium 0.5 nmol/ml and ascorbic acid oxidase (derived from cucumber) 4.5 units/ml) were added, incubated at 37°C for 5 min, and the absorbance at 600 nm was measured. It was measured. Triglyceride concentration (mg/1
00ml) is (absorbance of sample/absorbance of standard)
*Calculated based on 300. To measure total cholesterol,
Nescot TC Kitto-K (Nippon Shoji) was used. That is, 10 μl of serum was mixed with a coloring reagent (330 μg of phenol).
/ml of cholesterol-lesterase (Chromob
(derived from acterium Viscosum) 156un
its/ml, cholesterol oxidase (Stre
ptomyces Cinnamoneus) 0.
156 units/ml, 4-aminoantipyrine 0.
Add 1.5 ml of 125 mg/ml) and heat at 37°C for 15 minutes.
After incubating for 1 min, the absorbance at 500 nm was measured. The total cholesterol concentration (mg/100ml) was calculated by (absorbance of sample/absorbance of standard) x 300. H
HDL-cholesterol for DL-cholesterol
It was measured using Rootest Wako (Wako Pure Chemical Industries, Ltd.). That is, add 1 ml of precipitation reagent (heparin, 0.44% manganese salt solution containing 1% methanol) to 25 μl of serum,
After mixing, the mixture was left at room temperature for 10 minutes. After centrifugation at 10,000 rpm for 10 minutes, supernatant 0.5
ml of coloring reagent (0.1% p-chlorophenol, tris(hydroxymethyl)aminomethane, surfactant) and 75 mU/ml each of cholesterol ester hydrolase and cholesterol oxidase, peroxidase. Add 1 ml of 84 ng/ml each of 4-aminoantipyrine and 4-aminoantipyrine) and incubate at 37°C for 10 minutes.
I did it. Applying the absorbance of the reaction solution at 505 nm to the following formula, the amount of HDL-cholesterol (mg/100ml)
was calculated. HDL-cholesterol (mg/100ml) = (absorbance of sample / absorbance of standard) x 100
【００１０】結果
ＳＤ系ラツトにリパ−ゼインヒビタ−を経口投与し、血
清中のトリグリセライド、総コレステロ−ル、ＨＤＬ−
コレステロ−ル含量の変動を調べた。それらの結果を表
１、表２と表３に示した。Results: Lipase inhibitors were orally administered to SD rats, and serum triglycerides, total cholesterol, and HDL-
Changes in cholesterol content were investigated. The results are shown in Tables 1, 2 and 3.
【００１１】[0011]
【００１２】0012
【００１３】[0013]
Claims (7)
に対する特異的インヒビタ−をヒト又は動物に経口投与
することにより、食物由来の脂質の消化・吸収を抑制又
は阻害する。Claims: 1. Digestion and absorption of food-derived lipids is suppressed or inhibited by orally administering a specific inhibitor to soybean- or grain-derived gastric and pancreatic lipase to humans or animals.
ロ−ル血症の治療及び予防法。2. A method for treating and preventing hypercholesterolemia according to the items described in claim 1.
セライド血症の治療及び予防法。3. A method for treating and preventing hypertriglyceridemia according to the items described in claim 1.
及び予防法。4. A method for treating and preventing obesity according to the item described in claim 1.
ビタ−の使用状態を粉末とする。5. The lipase inhibitor according to claim 1 is used in the form of a powder.
ビタ−の使用状態を液状とする。6. The lipase inhibitor according to claim 1 is used in a liquid state.
ビタ−を所望の形で食品に混入できることを特徴とする
。7. The lipase inhibitor according to claim 1 can be mixed into foods in a desired form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3121892A JPH04327536A (en) | 1991-04-25 | 1991-04-25 | Method for treating and preventing hyperlipidemia and obesity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3121892A JPH04327536A (en) | 1991-04-25 | 1991-04-25 | Method for treating and preventing hyperlipidemia and obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04327536A true JPH04327536A (en) | 1992-11-17 |
Family
ID=14822493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3121892A Pending JPH04327536A (en) | 1991-04-25 | 1991-04-25 | Method for treating and preventing hyperlipidemia and obesity |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04327536A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0631727A1 (en) * | 1993-06-25 | 1995-01-04 | Yakurigaku Chuo Kenkyusho | Lipase inhibitor derived from a defatted rice germ |
| JPH0812585A (en) * | 1994-06-23 | 1996-01-16 | Lotte Co Ltd | Agent for lowering lipid in blood and food and beverage containing the same |
-
1991
- 1991-04-25 JP JP3121892A patent/JPH04327536A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0631727A1 (en) * | 1993-06-25 | 1995-01-04 | Yakurigaku Chuo Kenkyusho | Lipase inhibitor derived from a defatted rice germ |
| JPH0812585A (en) * | 1994-06-23 | 1996-01-16 | Lotte Co Ltd | Agent for lowering lipid in blood and food and beverage containing the same |
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