JP2005187476A - Ameliorant for lipid in blood and food additive - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a derivative exhibiting remarkably effective action on ameliorating lipid in blood which is a reason of cardiovascular disease such as arteriosclerosis, etc., compared to conventional highly unsaturated fatty acid and to provide an additive for food which ameliorates lipid in blood. <P>SOLUTION: The ameliorant for lipids in blood and food additive is a phospholipid comprising ≥15 mass.% of docosahexaenoic acid as a constituent fatty acid, eicosapentaenoic acid as a constituent fatty acid, and ≤60 mass.% of a phosphatidylethanolamine. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention uses docosahexaenoic acid as a constituent fatty acid, which has a blood lipid improving action that reduces the content of factors that cause arteriosclerosis such as total cholesterol and neutral lipid, and increases the content of high-density lipoprotein cholesterol. The present invention relates to a blood lipid improving agent and a food additive containing a phospholipid.

The n-3 series highly unsaturated fatty acids, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are known to have an effect of preventing vascular diseases such as arteriosclerosis. In this case, these polyunsaturated fatty acids have been tested in the form of triglycerides or ethyl esters which are readily available in large quantities. As a result of this study, EPA lowers plasma neutral lipids than ALA and DHA, whereas DHA lowers plasma cholesterol and phospholipids compared to EPA and ALA. It is also known. Atherosclerosis is a multifactorial disease that is thought to be promoted by increased cholesterol and triglycerides and decreased high-density lipoprotein cholesterol as factors in the blood [Haruo Nakamura, “Lipid metabolism and disease. / Nutrition and disease of fats and oils ", Yukishobo, (1990), pp. 385-396]. Therefore, in order to prevent or treat vascular diseases such as arteriosclerosis, it has been desired to develop drugs and the like that exhibit a more marked improvement effect on these blood lipids in general.
Haruo Nakamura, “Metabolism and Disease of Lipids / Nutrition and Disease of Fats and Oils”, Yukishobo, (1990), pp. 385-396

  An object of the present invention is to provide a drug exhibiting a more remarkable and effective action for improving blood lipids causing vascular diseases such as arteriosclerosis, and a food additive for improving blood lipids. is there.

  As a result of intensive studies to solve the above problems, the present inventors have found that phospholipids containing DHA as a constituent fatty acid, particularly phospholipids containing 10% or more of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and / or phosphatidylserine. Has been found to exhibit higher blood density cholesterol and neutral lipid lowering effects and higher density lipoprotein cholesterol increasing effects than triglycerides containing the same amount of DHA, leading to the completion of the present invention. It was.

That is, the present invention
[1] A blood lipid improving agent comprising phospholipid containing docosahexaenoic acid as a constituent fatty acid in an amount of 15% by weight or more and containing eicosapentaenoic acid as a constituent fatty acid,
[2] The blood lipid improving agent according to the above [1], wherein the content of phosphadylethanolamine is less than 60% by mass,
[3] A food additive containing phospholipids containing docosahexaenoic acid as a constituent fatty acid in an amount of 15% by mass or more and eicosapentaenoic acid as a constituent fatty acid, and having a blood lipid improving action,
[4] The food additive having a blood lipid improving action according to the above [3], wherein the content of phosphadylethanolamine is less than 60% by mass.

  The blood lipid improving agent and food additive of the present invention have the action of reducing the total cholesterol and neutral lipid content and increasing the high-density lipoprotein cholesterol content, and prevent vascular diseases such as arteriosclerosis Can be used for improvement.

  The phospholipid according to the present invention is a phospholipid containing 10% or more of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and / or phosphatidylserine, and is an effect of being a phospholipid containing docosahexaenoic acid as a constituent fatty acid. This is preferable.

  The blood lipid improving action in the present invention refers to an action of increasing or at least maintaining a lipid that is a preventive factor for the disease, while reducing the content of lipids causing vascular diseases such as arteriosclerosis, For example, it refers to the action of reducing total cholesterol and / or neutral lipid content and increasing high density lipoprotein cholesterol.

  The phospholipid according to the present invention is characterized by containing DHA as a constituent fatty acid, and particularly exhibits an excellent action of occupying 5% or more of DHA, further 15% or more, more effectively 30% or more of DHA. This is preferable. A phospholipid mixture containing DHA as a constituent fatty acid is obtained from natural materials such as squid skin, egg yolk, krill, DHA-producing microalgae (JP-A-7-95875), and DHA-producing microorganisms (JP-A-1-199588). In addition to being obtained by extraction according to JP-A-1-31189, 6-321970, 7-68157, synthesis (for example, JP-A-51-91213, 52-89622, 61-129191), transesterification using an enzyme ( For example, Y. Totani and S. Hara, J. Am. Oil Chem. Soc., 68, 848-851 (1991), Masafumi Hosokawa, Hiroaki Oshima, Hiroyuki Kono, Kotaro Takahashi, Rokuo Hanedano, Ikuo Odajima, Journal of Japanese Fisheries Society, 59, 309 (1993)) or incorporation into bacterial phospholipids (eg K. Watanabe, C. Ishikawa, H. Inoue, D, Cenhua, K. Yazawa and K. Kondo, J. Am. Oil Chem. Soc., 71, 325-330 (1994)).

  For example, the main composition of phospholipids extracted from squid skin is usually 40-70% phosphatidylcholine, 10-30% phosphatidylethanolamine, and 5-15% phosphatidylserine. DHA in each constituent fatty acid is 40 to 60% for phosphatidylcholine, 15 to 25% for phosphatidylethanolamine, and 20 to 30% for phosphatidylserine. %. Therefore, the phospholipid obtained from the cuttlefish skin is an example of a preferred phospholipid in the present invention.

  Since such DHA-containing phospholipids are amphiphilic, they can be easily mixed into any food regardless of water-solubility or oiliness, and can be widely added to foods or used as health foods themselves.

  The blood lipid improving agent of the present invention can be administered orally or parenterally for treatment. Oral administration agents can be solid preparations such as powders, granules, capsules and tablets, or liquid preparations such as syrups and elixirs. Moreover, it can be set as an injection, a mucosa administration agent, and an external preparation as a parenteral administration agent. These preparations are produced according to a conventional method by adding a pharmacologically and pharmaceutically acceptable production aid to the active ingredient. Furthermore, it is possible to obtain a sustained-release preparation by a known technique. When using the said manufacturing aid, the compounding quantity of the phospholipid in the chemical | medical agent of this invention is 0.1 to 50 weight% normally, Preferably it is 0.2 to 10 weight%.

  Administration of internal preparations (oral preparations), injectable preparations (injection preparations), mucosal administration preparations (buccals, troches, suppositories, etc.), external preparations (ointments, medicated creams, patches, etc.) Appropriate pharmaceutical ingredients according to the route are used. For example, in the case of oral preparations and mucosal administration agents, excipients (eg starch, lactose, crystalline cellulose, calcium lactate, magnesium aluminate metasilicate, silicic anhydride, mannitol), binders (eg hydroxypropylcellulose, Polyvinylpyrrolidone etc.), disintegrating agents (eg: carboxymethylcellulose, carboxymethylcellulose calcium), lubricants (eg: magnesium stearate, talc), coating agents (eg: hydroxyethylcellulose), flavoring agents, etc. For injections, solubilizers or solubilizers that can constitute aqueous injections (eg, distilled water for injection, physiological saline, propylene glycol), suspension agents (eg, surfactants such as polysorbate 80) , Ingredients for pharmaceutical preparations such as pH adjusters (eg organic acids or their metal salts), stabilizers, etc. Furthermore, for external preparations, aqueous or oil-based solubilizers or solubilizers (eg alcohols, fatty acid esters), adhesives (eg carboxyvinyl polymers, polysaccharides), emulsifiers (eg surfactants) Pharmaceutical ingredients such as stabilizers are used.

  The drug of the present invention having the above-described configuration can be produced by a known production method, for example, the method described in the Japanese Pharmacopoeia 10th Edition General Rules for Preparations or a method with appropriate improvements.

  Although the dosage of the drug of the present invention varies depending on the administration form, it is usually 1 to 1500 mg as DHA in the case of treating an adult, and it is preferable to administer this in 2 to 3 times a day. This dosage can be increased or decreased depending on the age, weight and symptoms of the patient.

  In addition, the food additive of the present invention includes processed bean products such as tofu and natto; bread, cakes, castella, cookies, pudding, jelly, ice cream, konjac; processed fish products such as bamboo rings and salmon; instant ramen and noodles It can be added to various foods including dairy products such as cheese, butter and yogurt; meat processed products such as hamburger, ham and sausage. The amount added to food varies depending on the food, but is usually about 10 mg to 10 g / 100 g as DHA.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to this.

Example 1
A phospholipid extracted from squid skin was used as the phospholipid. Its main composition was 63.1% phosphatidylcholine, 21.2% phosphatidylethanolamine, and 9.1% phosphatidylserine. The DHA in each constituent fatty acid is 44.4% for phosphatidylcholine, 18.0% for phosphatidylethanolamine and 24.5% for phosphatidylserine, and 33.4% for DHA in the total phospholipids. It was. DHA-containing triglycerides having a fatty acid composition similar to that of this DHA-containing phospholipid are mixed with various fatty acid triglycerides such as DHA triglycerides (DHA 35-50%), EPA triglycerides (EPA 95%), arachidonic acid (AA) triglycerides (AA 25%). ), Tripalmitin (100% palmitic acid) was mixed. Two spontaneously hypertensive rats (SH rats) were divided into 4 groups, and a basic diet was prepared by adding 1% cholesterol and 0.5% sodium cholate to a commercial diet. Feed containing phospholipids containing DHA equivalent to 7%; Group B containing phospholipids containing DHA equivalent to 0.35% DHA relative to the basal feed; Group C containing 0.7% DHA compared to the basal feed Feed containing the corresponding DHA-containing triglyceride; Group D was fed a diet containing DHA-containing triglyceride equivalent to 0.35% DHA at a rate of 20 g per day for 2 weeks. After the test, blood was collected from rats by an abdominal aortic puncture under ether anesthesia, and plasma was fractionated to analyze lipids. The results are shown in FIG. Total cholesterol and neutral lipids were the lowest in group A, and high density lipoprotein cholesterol was the highest in group A.

Example 2
A DHA-containing triglyceride having a fatty acid composition similar to that of the DHA-containing phospholipid was prepared in the same manner as in Example 1. SD rats were divided into 3 groups of 6 rats, group E was the same as in Example 1, basic diet; group F was a diet containing DHA-containing phospholipids equivalent to 0.7% of DHA relative to the basic diet; group G was basic A feed containing DHA-containing triglycerides corresponding to 0.7% of DHA was given to the feed for 24 weeks at 24 g per day. After the test, blood was collected from rats by an abdominal aortic puncture under ether anesthesia, and plasma was fractionated to analyze lipids. The results are shown in FIG. Total cholesterol and neutral lipids were the lowest in the F group, and clearly lower than the control E group. Conversely, high density lipoprotein cholesterol was highest in group F and higher than in group E. The decrease in the F group and the increase in the high density lipoprotein cholesterol in the total cholesterol level were statistically significant as compared with the E group and the G group to which the same amount of DHA-containing triglyceride was administered.

2 is a graph showing the mean value and standard deviation for each group of blood total lipid (TC), neutral lipid (TG), and high density lipoprotein cholesterol (HDL-C) analyzed in Example 1. FIG. 2 is a graph showing the mean value and standard deviation for each group of total blood lipid (TC), neutral lipid (TG), and high-density lipoprotein cholesterol (HDL-C) analyzed in Example 2. FIG.

Claims (4)

A blood lipid improving agent comprising a phospholipid containing docosahexaenoic acid as a constituent fatty acid in an amount of 15% by mass or more and eicosapentaenoic acid as a constituent fatty acid as an active ingredient. The blood lipid improving agent according to claim 1, wherein the content of phosphadylethanolamine is less than 60% by mass. A food additive comprising a phospholipid containing docosahexaenoic acid as a constituent fatty acid in an amount of 15% by mass or more and eicosapentaenoic acid as a constituent fatty acid, and having a blood lipid improving action. The food additive having a blood lipid improving action according to claim 3, wherein the content of phosphadylethanolamine is less than 60% by mass.

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