JPH0930962A - Medical oil-containing composition - Google Patents

Abstract

(57) [Summary] [Structure] An n-3 long-chain polyunsaturated fatty acid is contained as a constituent fatty acid of glyceride, and less than 40 mol% of the total amount of the n-3 long-chain polyunsaturated fatty acid is 2% of the glyceride. Or a fluid containing a fat or oil containing mixed triglyceride bonded to the position, or a fat or oil containing the mixed triglyceride,
A composition containing medical fats and oils such as a fat emulsion. [Effect] The oil-and-fat-containing composition of the present invention has a lower blood cholesterol level and / or a lower blood triglyceride level than the conventional composition containing the same amount of the n-3 long-chain polyunsaturated fatty acid source. Has a large effect (improving effect on blood lipid concentration), and has a large effect (increasing platelet aggregation ability suppressing effect) on increasing eicosanoid PGI ₂ production amount and decreasing TXA ₂ production amount.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical oil and fat-containing composition which has a high effect of reducing the content of neutral lipids and cholesterol in blood and suppressing the platelet aggregation ability.

[0002]

2. Description of the Related Art In recent years, hyperlipidemia diseases in which blood neutral lipid (triglyceride) and cholesterol levels are high are increasing due to diversification of dietary habits, excessive intake of calories, and other factors. . Hyperlipidemia is considered to be a risk factor that eventually causes symptoms such as ischemic heart disease and arteriosclerosis.

There is a positive correlation between the serum cholesterol level and the risk of developing ischemic heart disease, and epidemiology indicates that lowering the serum cholesterol level also decreases the risk of developing ischemic heart disease. It has been clarified from the results of the survey (for example, Yu Mizushima et al., "Today's Therapeutics (1993 Edition)", p. 361, Nankodo). In addition to hypertriglyceridemia leading to the development of fatty liver, pancreatitis, etc., it has been pointed out that it is a risk factor for ischemic heart disease. Therefore, clinically, hypercholesterolemia and hypertriglyceridemia have become a major problem among hyperlipidemias, and as a countermeasure against this, generally, the intake of calories etc. is restricted for hyperlipidemic patients. In addition to the diet therapy, the treatment is carried out by administration of antihyperlipidemic agents such as clofibrate, cholestyramine nicotinate, tocopherol nicotinate, soysterol and dextran sulfate.

Among the arteriosclerosis, atherosclerosis is fat deposition or plaque formation on the intima of coronary arteries, basilar arteries, renal arteries, thoracic / abdominal aorta, etc. Abnormal accumulation of lipids such as cholesterol and cholesterol is considered to be a major cause. In arteriosclerosis, platelet adhesion and aggregation are promoted in combination with abnormal blood vessel walls and abnormal blood flow, and eventually progress to arterial thrombosis. For the treatment of arterial thrombosis using drugs, antiplatelet therapy mainly consisting of platelet aggregation inhibitors (eg warfarin, aspirin, etc.) and thrombolytic agents (eg urokinase, streptokinase etc.) for dissolving the formed thrombus and embolus. Is widely used.

Eicosanoids such as prostaglandins and thromboxane, which are synthesized from polyunsaturated fatty acids in vivo, have platelet aggregation and vasoconstriction actions, and conversely have platelet aggregation inhibitory action and vasodilation action. It is known that these eicosanoids are closely associated with the development of arteriosclerosis. Among eicosanoids, prostaglandin I ₂ (hereinafter sometimes abbreviated as PGI ₂ ) has a platelet aggregation inhibitory action, a vasodilatory action and a blood pressure lowering action, and thromboxane A ₂ (hereinafter referred to as TXA ₂ Is sometimes abbreviated) is known to have a platelet aggregation-inducing action and a vasoconstrictor action.

[0006] As described above, when the blood lipid concentration, especially the blood cholesterol and blood triglyceride concentration becomes high, hyperlipidemia develops, which eventually causes symptoms such as ischemic heart disease, and the blood lipid concentration increases. It is said that abnormal accumulation in the inner wall of blood vessels promotes adhesion and aggregation of platelets, leads to the formation of arterial thrombus, and causes symptoms such as atherosclerosis. It is known to be closely associated with blood pressure, ischemic heart disease, platelet aggregation, arteriosclerotic disease, arterial thrombus formation, and the like.

[0007] By the way, some of the raw materials used for ordinary meals contain ingredients that reduce the concentrations of blood cholesterol and blood triglyceride. For example, the soysterol is an unsaponifiable sterol contained in soybean, and JP-A-3-53866 discloses a lignan compound derived from sesame oil, and foods and drinks such as butter and mayonnaise containing the same are disclosed. Proposed. Eicosapentaenoic acid (C _{20: 5} , where the number after C represents the total number of carbons: the number of double bonds. The same applies hereinafter. All cis-5, 8, 11,
14,17-eicosapentaenoic acid, hereinafter abbreviated as EPA. ) And docosahexaenoic acid (C _{22: 6} , total cis-4,
7,10,13,16,19-docosahexaenoic acid,
Hereinafter abbreviated as DHA. It has been revealed by animal experiments and clinical experiments that n-3 long-chain polyunsaturated fatty acids and food materials containing them have the action of reducing serum cholesterol levels and triglyceride levels. Robinson, DR et al., J. Lipid Res., Vol. 34, Vol.
435, 1993).

The mechanism of action of lowering serum cholesterol levels caused by ingestion or administration of EPA or DHA is as follows. In the liver, n-3 long-chain polyunsaturated fatty acids or oils and fats containing them are taken up in the liver. It is presumed that the ability of cholesterol synthesis in humans is suppressed, and as a result, the release of cholesterol into blood is suppressed (Ch
oi, YS et al., Lipids, 24, 45, 1989.
Year). Moreover, it is speculated that the decrease in serum triglyceride level is due to the fact that n-3 long-chain polyunsaturated fatty acids suppress the triglyceride synthesizing ability in the liver.
Kenji, "Fats and Oils", Vol. 46, No. 4, p. 90, 199.
3 years).

It is also known that n-3 long-chain polyunsaturated fatty acids such as EPA and DHA suppress the platelet aggregation action. That is, according to an epidemiological survey, a significant correlation was observed between ingestion of n-3 long-chain polyunsaturated fatty acids, suppression of platelet aggregation ability, and decrease in whole blood viscosity, and cardiovascular disease and cerebrovascular disease. It has been reported that there is an inverse correlation with the mortality rate due to the disease or a reduction in the mortality rate due to the disease (Hirai, A. et al., Lancet, Vol. 2, page 1132, 19).
80 years). As a mechanism for reducing the mortality rate due to ischemic heart disease due to ingestion of n-3 long-chain polyunsaturated fatty acid, antiplatelet aggregation action, plasma lipid improving action and the like are considered.

Therefore, in order to reduce the blood cholesterol level and the blood triglyceride level, or to suppress the platelet aggregation, to prevent hyperlipidemia and to improve the blood lipid level in hyperlipidemic patients. EPA and DHA for the purpose of prevention and treatment of arteriosclerosis
Intentionally ingesting foods containing a large amount of fish containing
Commercially available infant formula, health foods and the like, which are made of fish oils containing PA and DHA, fish oil concentrates and the like. However, it is said that these need to be ingested or administered in large amounts over a long period of time.

Fish oils containing n-3 long chain polyunsaturated fatty acids such as EPA and DHA are mainly sardine oil, cod liver oil,
Herring oil, squid oil, tuna orbital oil, and the like are used, and the chemical structure of these oils and fats is 50% of the total amount of the n-3 long-chain polyunsaturated fatty acid present by ester bond to triglyceride. Mol% or more is present as the constituent fatty acid at the 2-position of the triglyceride, in other words, the n-3 long-chain polyunsaturated fatty acid has a structure in which a larger amount of ester bond is present at the 2-position than at the 1- and 3-positions of the triglyceride. .

On the other hand, n-3 long-chain polyunsaturated fatty acids such as EPA and DHA have the effect of reducing blood lipids and the effect of suppressing platelet aggregation as described above, but they are usually It is also known that compared with the structural fatty acids of edible vegetable oils and fats, they have many double bonds in the molecule and are therefore easily oxidized, and when ingested in excess, they are known to have harmful effects on the living body. When the peroxidation reaction of lipids progresses in vivo, it causes damage to biological membranes, causing ischemic heart disease, arteriosclerosis, cataract, cancer,
It has been speculated that it may cause Alzheimer's disease, collagen disease, amyloidosis, and other lesions.

By the way, hyperlipidemia is caused by nephrotic syndrome,
It often occurs as a secondary disease such as obstructive biliary tract disease, hypothyroidism, and diabetes, and when the condition becomes severe in arteriosclerosis, the patient's appetite and digestion are diminished as in the case of other diseases. Decreased absorption function occurs. Means such as liquid foods, infusions, and fat emulsions have been adopted in order to medically provide nutrition or calorie supplement to cope with such symptoms.

Liquid diet is a treatment applicable to patients with poor nutrition or poor digestion and absorption function, which has good digestibility and absorbability and has little mechanical irritation to digestive tract due to digestive residue It is food. It is often taken orally, but depending on the patient's condition, liquid food may be given enterally by tube. Liquid foods include natural concentrated liquid foods, semi-digestive and component nutrients, and the ingredients are cereals, potatoes, beans, eggs, milk and dairy products, vegetables, fruits, seafood and meats, butter and vegetable oils and fats. , Sugar, etc.

The infusion solution is used for the purpose of maintaining nutrition when the oral intake is not possible or when oral intake or administration is insufficient, correcting and maintaining the equilibrium of water and electrolytes, and maintaining circulating blood volume. Nutrition infusions include carbohydrate infusions, amino acid infusions and fat emulsions.

The fat emulsion contains triglyceride, phospholipid, glycerin and the like. It has a high energy content, and unlike sugar transfusions, it does not cause osmotic diuresis. The fat emulsion used to maintain nutrition is used mainly for the purpose of supplying energy sources and essential fatty acids (linoleic acid, etc.) during high-calorie infusion therapy.
It is administered from a peripheral vein by mixing with a basic solution for high calorie infusion so that the total amount of calories administered is about 10%.

[0017]

SUMMARY OF THE INVENTION The present invention has been made in view of such a situation as described above, and an object of the present invention is to have no side effects on humans and animals and to obtain the conventional n-3 system. An object of the present invention is to provide a medical oil / fat-containing composition having a high effect of reducing blood lipid concentration and suppressing platelet aggregation ability by using a smaller amount than a long-chain polyunsaturated fatty acid source.

[0018]

Means for Solving the Problems As a result of intensive studies aimed at achieving the above object, the present inventors have found that n-3 long-chain polyunsaturated fatty acids at the 1-position and / or 3-position of a glyceride structure. The oils and fats with a large distribution of
-3 type long-chain polyunsaturated fatty acids are widely distributed, compared with general n-3 long-chain polyunsaturated fatty acid sources such as fish oil,
It has been found that the above-mentioned object is achieved because the effect of reducing the blood cholesterol level and / or the blood triglyceride level is extremely high and the effect of suppressing the platelet aggregation ability is remarkably large. The present invention has been completed based on such findings.

That is, the gist of the present invention is to include an n-3 long-chain polyunsaturated fatty acid as a constituent fatty acid of glyceride,
An oil-and-fat-containing composition for medical use, in which less than 40 mol% of the total amount of n-3 long-chain polyunsaturated fatty acids is mixed triglyceride bonded to the 2-position of the glyceride or an oil or fat containing the mixed triglyceride is blended. Is.

The mixed triglyceride featured in the present invention is a triglyceride composed of a fatty acid containing an n-3 long-chain polyunsaturated fatty acid and glycerin,
When the total amount of the n-3 long-chain polyunsaturated fatty acids is 100 mol%, less than 40 mol% thereof and any fatty acid other than the n-3 long-chain polyunsaturated fatty acids are in the second position of the triglyceride. Ester-bonded, and 60 mol% or more of the n-3 long-chain polyunsaturated fatty acid and any fatty acid other than the n-3 long-chain polyunsaturated fatty acid are present at the 1- and 3-positions of the triglyceride. An ester bond is distributed randomly or non-randomly.

The term "n-3 long-chain polyunsaturated fatty acid" as used herein means an n-3 straight-chain unsaturated fatty acid having 18 or more carbon atoms and 3 or more double bonds, specifically α -Linolenic acid (C _{18: 3} ), octadecatetraenoic acid (C _{18: 4} , 6,
9,12,15-octadecatetraenoic acid), arachidonic acid (C20 _{: 4} ), EPA (C20 _{: 5} ), docosapentaenoic acid (C22 _{: 5} , 7,10,13,16,19-docosape)
ntaenoic acid), DHA (C _{22: 6} ) and the like. In the present invention, among these, α-linolenic acid,
Arachidonic acid, EPA, docosapentaenoic acid and DH
One or two or more kinds of mixed fatty acids selected from the group consisting of A in any proportion are preferable, and EPA and / or DHA are more preferable.

As the fatty acid other than the n-3 long-chain polyunsaturated fatty acid, any of short-chain, medium-chain and long-chain fatty acids and saturated and unsaturated fatty acids can be used. A straight-chain, medium- or long-chain saturated or unsaturated fatty acid having 6 or more carbon atoms is preferable. Such fatty acids include caproic acid (C _{6: 0} ), caprylic acid (C _{8: 0} ), capric acid (C _{10: 0} ), lauric acid (C _{12: 0} ), myristic acid (C _{14: 0} ), palmitic acid. (C _{16: 0} ), palmitooleic acid (C _{16: 1} ), stearic acid (C _{18: 0} ), oleic acid (C _{18: 1} ), elaidic acid (C _{18: 1} ), linoleic acid (C _{18 : 2} ), α′-linolenic acid (C _{18: 3} , 5,8,11-octadecatrienoic acid), γ
-Linolenic acid ( _C18: 3,6,9,12-octadecatrienoic acid), Eleostearic acid ( _C18: 3,9,11,1)
3-octadecatrienoic acid), arachidic acid (C _{20: 0} ), gadoleic acid (C _{20: 1} ), behenic acid (C
_{22: 0} ), erucic acid (C _{22: 1} ), brassic acid (C _{22: 1} ).
Etc. can be given. These fatty acids may be used alone or may be used as mixed fatty acids in any proportion. Among these, myristic acid,
Palmitic acid, stearic acid, oleic acid, linoleic acid and the like are preferable.

In order to produce the mixed triglyceride according to the present invention composed of the n-3 long-chain polyunsaturated fatty acid and other fatty acids mentioned above, a chemical synthesis method, a transesterification method, or a natural product is used. A technique such as an extraction method may be used. Examples of the chemical synthesis method include a desired amount and composition of a fatty acid, a fatty acid anhydride or a fatty acid halide (fatty acid chloride) and glycerin, an acidic substance (hydrochloric acid, sulfuric acid, paratoluenesulfonic acid, etc.), an alkaline substance (hydroxylation). Esters of sodium, potassium hydroxide, etc.), metals (zinc, tin, titanium, nickel, etc.), metal oxides (zinc oxide, alumina, ferrous oxide, etc.), metal halides (aluminum chloride, tin chloride, etc.) In the presence or absence of a hydrogenation catalyst in a nitrogen gas stream of 100 to 2
It is preferable that the esterification reaction is carried out for 1 to 25 hours while heating to 50 ° C. and removing the produced water.

The esterification product may be subjected to alkali deoxidation treatment, activated carbon, activated clay, alumina, silica gel, if necessary.
Free fatty acids, monoglycerides, diglycerides, which are subjected to adsorption / fractionation treatment using an ion exchange resin or the like, solvent separation treatment using a hydrophilic organic solvent such as methanol or ethanol and / or a lipophilic organic solvent such as n-hexane or xylene, Impurities such as coloring substances and odorous components are removed, and these treatments are appropriately combined to obtain triglyceride
The content of the n-3 long-chain polyunsaturated fatty acid residues bonded to the position is the total of the n-3 long-chain polyunsaturated fatty acid residues bonded to the 1st, 2nd and 3rd positions of the triglyceride. 40 of content
The triglyceride component may be fractionated or concentrated so as to be less than mol%. The mixed triglyceride according to the present invention is preferably deodorized by blowing steam under heating and under reduced pressure.

To obtain the mixed triglyceride according to the present invention by using the transesterification method, for example, n-3 as a raw material is used.
Triglycerides of fatty acids containing a large amount of long-chain polyunsaturated fatty acids (component a-1) and fatty acids containing substantially no or a small amount of n-3 long-chain polyunsaturated fatty acids (component a-
2), lower alcohol ester of component a-2 (methyl ester, ethyl ester, etc .; hereinafter the same) or component a
-2 triglyceride in a desired ratio, or a triglyceride of fatty acid (component b-1) containing substantially no or a small amount of n-3 long-chain polyunsaturated fatty acid and n-.
A required amount of a fatty acid (component b-2) containing a large amount of 3 type long-chain polyunsaturated fatty acid or a lower alcohol ester of component b-2 is mixed, and an alkaline substance such as sodium hydroxide or potassium hydroxide is used as a catalyst. , Metal alkoxides such as sodium methylate, sodium ethylate and lithium butyrate, basic anion exchange resins, ion exchange resins such as acidic cation exchange resins,
Alternatively, it is convenient to carry out the transesterification reaction using lipase. When transesterification is carried out using a specific lipase as a catalyst, a new fatty acid group can be selectively introduced at the 1-position and 3-position of the triglyceride, as will be described later, and the method for producing the mixed triglyceride according to the present invention. As desirable.

The raw materials for the transesterification are vegetable oils such as linseed oil, sesame oil, perilla oil, etc. as component a-1, fish oils such as sardine oil, cod liver oil, herring oil, squid oil, tuna orbital oil, whales, seals, Pressed or extracted oil obtained from the origin of marine mammals such as fur seals, milk fat of the animals, chlorella, spirulina, donariella, etc.
), Crypthecodinium (eg Crypthecodinium
cohnii), isochrysis (eg Isochrysis galban
a) Oils and fats extracted from microalgae belonging to, etc., oils and fats derived from microorganisms of the genus Mortierella, etc., and n-3 long-chain polyunsaturated fatty acids or the above-mentioned various fatty acids containing this in any proportion. (Refer to paragraph 0022)
Triglycerides of mixed fatty acids with can be used. Component a
As -2, various fatty acids or their derivatives described in paragraph 0022 can be used.

As component b-1, there are triglycerides obtained from plants, animals, microbes, microalgae, etc., soybean oil,
Rapeseed oil, cottonseed oil, corn oil, palm oil, palm oil, safflower oil, high oleic safflower oil, sunflower oil, high oleic sunflower oil, olive oil, peanut oil, cacao butter, chinese tallow, sal butter, shea butter, Beef tallow, lard, hydrogenated oils and fats thereof, fractionated oils and fats, and the component a
Examples of the triglyceride of No. 2, medium-chain fatty acid triglyceride and the like can be exemplified, and as the component b-2, there is a fatty acid obtained by the hydrolysis treatment of the component a-1.

In the transesterification reaction, as an example, the above raw materials are mixed in a molar ratio of component a-1: component a-2 = 1: 0.1.
5, component b-1: component b-2 = 1: 2 to 10 are mixed, and when an alkali or a metal alcoholate is used as a catalyst, it is in an anhydrous state and is 0.5 to 0.5 at 80 to 120 ° C. Allow transesterification for 3 hours. Similarly, when an ion exchange resin is used, the raw material is made anhydrous, but it is preferable to circulate and contact the raw material in a column system at room temperature to 40 ° C. When using lipase as a catalyst, the water content in the raw material is set to 1% by weight or less, and commercially available lipase powder or a known carrier such as celite, diatomaceous earth, activated carbon, porous glass, ion exchange resin, chitosan, high Immobilized lipase immobilized on molecular gel, cellulose powder or the like is added, and transesterification reaction is performed at 20 to 80 ° C. for 0.5 to 20 hours.

As the lipase, those originating from the following microorganisms or originating from animal organs can be used. That is, Aspergillus (eg Aspergillus niger), Mucor (eg Mucor miehei), Candida (eg Candida cyrindracea), Pseudomonas (eg Pseudomonas fragi), Alcaligenes (eg,
Alcaligenes s described in JP-B-58-36953
p.), Rhizopus delemar (for example, Rhizopus delemar), Geotrichum candidum (for example), and lipases of microbial origin and pancreatic lipases for pigs and the like. Of these, lipases originating from microorganisms of the genus Aspergillus, genus Mucor, genus Alcaligenes and genus Rhizopus, and porcine pancreatic lipase specifically act on the 1- and 3-positions of glycerides, and therefore, when producing the mixed triglyceride according to the present invention. Is preferred.

The transesterification reaction product obtained by the various transesterification methods described above can be the mixed triglyceride used in the present invention depending on the kind of raw material selected, but it can be obtained by the chemical synthesis method. As with the esterification products obtained
If necessary, alkali deoxidation treatment, adsorption / fractionation treatment, solvent fractionation treatment or solvent-free fractionation (wintering) treatment, etc. are performed in an appropriate combination to remove impurities and fractionate or concentrate glyceride components. It can also be a mixed triglyceride used in the invention. The triglyceride is preferably deodorized.

The mixed triglyceride according to the present invention can also be obtained by a method of extracting fats and oils from a natural product. That is, among those described as the raw materials for transesterification (component a-1), whales and seals (harbor)
seal, harp seal, etc.), body tissues of marine mammals such as fur seals, milk secreted from the animals, cells of microalgae such as chlorella, spirulina, and Donaliella, or cultured cells thereof, Nannochloropsis genus,
Microalgae belonging to the genus Thraustochytrium, genus Crypthecodinium, genus Isochrysis, etc., for example Nannochloropsis oculata
), Trustchytrium aureum (Thraustochytr
ium aureum), Cryptecodynium cornie (Cry
pthecodinium cohnii), Isocrisis galvana (Iso
chrysis galbana) etc. or these cultured cells are used as raw materials. It should be noted that when the origin is a microorganism, the triglyceride obtained therefrom may be any one as long as it satisfies the glyceride structure of the present invention.

These are pressed or n-hexane,
Chloroform, benzene, diethyl ether, an organic solvent such as methanol is extracted or fractionated to obtain an oil, which is subjected to degumming, alkaline deoxidation, decolorization, deodorization, and other free fatty acid, phospholipid, The glyceride fraction can be obtained by removing impurities such as glycolipids, unsaponifiable substances, coloring substances and odorous components. This glyceride fraction can be used as the mixed triglyceride used in the present invention, and the glyceride fraction is further fractionated by solventless low temperature fractionation, solvent fractionation or a silica gel column to bind to the triglyceride at the 2-position. It is also possible to produce triglycerides with even fewer long chain polyunsaturated fatty acid residues.

The mixed triglyceride according to the present invention produced by the chemical synthesis method, the transesterification method, the extraction method from a natural product or the like as described above is an n-3 long chain polyvalent fatty acid as its constituent fatty acid. 40 of total unsaturated fatty acids
Less than mol% is an ester bond at the 2-position of triglyceride, but more preferably less than 20 mol%.
If it is 40 mol% or more, the desired effect of the present invention becomes small. The mixed triglyceride according to the present invention can be used as an oil and fat as it is, and it can be used as usual edible oil and fat such as component b-1.
It can also be used as an oil / fat by mixing with an animal / vegetable oil / fat as described above. At this time, the content of the mixed triglyceride according to the present invention is preferably 5 to 100% by weight, more preferably 10 to 100% by weight, based on the total fat and oil. Most preferably, it is 20 to 100% by weight. If it is less than 5% by weight, the desired effect of the present invention is small.

In the present invention, the oil and fat prepared by the above-mentioned method, that is, the triglyceride composed of the fatty acid containing the n-3 long-chain polyunsaturated fatty acid and glycerin, is the n-3 long-chain polyvalent. Less than 40 mol% of the total amount of unsaturated fatty acids and any fatty acids other than the n-3 long-chain polyunsaturated fatty acids are distributed in the 2-position of the triglyceride, and the n-3 long-chain polyunsaturated A mixed triglyceride in which 60 mol% or more of the total amount of fatty acids and any fatty acid other than the n-3 long-chain polyunsaturated fatty acid are randomly or non-randomly distributed at the 1- and 3-positions of the triglyceride to form an ester bond, respectively. Or a mixed triglyceride and any of the above-mentioned edible animal and vegetable oils and fats are blended so that the content of the mixed triglyceride is 5% by weight or more. Oil, medical fat-containing composition containing as an essential ingredient.

Since the fats and oils according to the present invention contain polyunsaturated fatty acids, they can be handled in the same manner as ordinary edible fats and oils, except for applications such as frying oil which is heat-treated for a long time. Can be processed with raw materials. To avoid quality deterioration, tocopherol, ascorbic acid ester (palmitate, stearate, etc.), β-carotene,
It does not matter if other antioxidants are added in appropriate amounts.

The medical fat and oil-containing composition referred to in the present invention includes capsules such as soft capsules and microcapsules, drinks whose viscosity is adjusted for patients with diseases, oral foods such as jelly, pudding, cookies and ice cream, and simple Ordinary liquid foods such as liquid foods, protein-added foods, maintenance liquid foods, etc., blender foods such as three-part porridge, five-part porridge, seven-part porridge, whole porridge, mixer foods, natural concentrated liquid foods, artificial concentrated liquid foods , Oral concentrated liquid foods such as mixed concentrated liquid foods, low protein liquid foods, low cholesterol liquid foods, oral or special liquid foods such as low sodium liquid foods, nutritional infusions and fats to be administrated intravenously It is possible to ingest or administer various medical foods and formulations including emulsions. The oil-and-fat-containing composition according to the present invention may be used in any form other than the above, as long as it does not depart from the gist of the present invention.

The content of the fats and oils according to the present invention in these medical fats-and-oils-containing compositions cannot be uniformly defined depending on the type and form of the composition, the conditions for ingesting or administering the composition, and the like. About 5% by weight or more, preferably 10 to 100% by weight, as the mixed triglyceride, based on the total fats and oils contained or added to the composition,
More preferably, it is 20 to 100% by weight. The oil / fat according to the present invention (that is, the oil / fat consisting only of the mixed triglyceride and the oil / fat containing 5% by weight or more of the mixed triglyceride) may be appropriately used in such a blending ratio. When the amount is less than the lower limit value, at least one of the effect of reducing the blood cholesterol level and / or the blood triglyceride level and the effect of suppressing the platelet aggregation ability becomes small. The method of blending the fats and oils according to the present invention with the medical fats and oils-containing composition of the present invention is not particularly limited, and the same operations as in the case of general edible fats and oils, mixing, dispersion, oil-in-water emulsification, The water-in-oil type may be emulsified, dissolved or solubilized and incorporated into the medical fat and oil-containing composition.

Of the medical oil and fat-containing composition of the present invention, for example, in the case of oral food and liquid food, various types of compositions are prepared by using the known raw materials for food and the oil and fat according to the present invention. You can At this time, the fat or oil according to the present invention is added to the raw material for food, or all or part of the fat or oil of the raw material for food is replaced with the fat or oil according to the present invention, and the present invention is applied to the entire oral food or liquid food. The content of the mixed triglyceride is 0.1% by weight or more, preferably 1
It may be about 80% by weight. If it is less than 0.1% by weight, the desired effect cannot be expected. The upper limit value can be appropriately set within a known range according to each type of oral food and liquid food. Further, in the case of a nutritional infusion or fat emulsion to be administered intravenously, purified water and the oil or fat according to the present invention, soybean as an emulsifier, lecithin of egg yolk origin, lysolecithin, fractions thereof (phosphatidylcholine, phosphatidylethanolamine, (Phosphatidylinositol and lyso forms thereof), a derivative in which the base moiety of lecithin is exchanged with an alcohol group (phosphatidylethanol, phosphatidylglycerol, etc.), Tween 80 or the like can be used for dispersion, emulsification or solubilization to prepare the preparation. The content of the mixed triglyceride according to the present invention relative to the whole is 0.1% by weight or more, preferably 1 to 3
It should be 0% by weight.

By ingesting or administering the medical fat / oil-containing composition of the present invention, blood cholesterol level and / or
Alternatively, the blood triglyceride level can be reduced and the platelet aggregation ability can be suppressed. Moreover, since these effects are remarkably large as compared with the case where fish oil or the like which is a conventional n-3 long-chain polyunsaturated fatty acid supply source is blended, even a small amount of use is recognized. Furthermore, the medical oil / fat-containing composition of the present invention can be used for applications such as the prevention and treatment of hyperlipidemia and the prevention and treatment of arteriosclerosis based on both the above effects.

[0040]

【Example】

Reference Example 1 1 kg of triolein and fish oil (manufactured by Tama Biochemical Co., Ltd., trade name: EPA-18) were hydrolyzed mixed fatty acids at low temperature fractionated fish oil hydrolyzed fatty acid concentrate (C _{20: 5} : 3 in total fatty acids).
7.4 mol%, C22 _{: 5} : 5.4 mol%, C22 _{: 6} : 25.
2 mol%. 72. as an n-3 long-chain polyunsaturated fatty acid.
5 mol%. Add 0.01 wt% BHT. ) With a molar ratio of 1: 5 to adjust the water content to 0.2% by weight, and then use lipozyme IM20 (trade name; lipase derived from Mucor miehei, manufactured by Novo Nordisk). Packed glass column (10cmφ × 60c
m) was allowed to undergo a selective transesterification reaction at 40 ° C.

After removing free fatty acids from the transesterification reaction product by steam distillation and washing with water, stainless steel filled with silica gel (Wako Pure Chemical Industries, Ltd., Wako Gel C100) infiltrated with n-hexane. The mixture was applied to a column and eluted with n-hexane to remove diglyceride to obtain 720 g of mixed triglyceride according to the present invention. The total fatty acid composition constituting the present triglyceride and the fatty acid compositions at the 1st, 3rd and 2nd positions of the glyceride were determined by GLC analysis. Table 1 shows the results. 90 mol% of C _{20: 5} constituting the present triglyceride. 95 mol% or more of C _{22: 6} , n
93.5 mol% of the total amount of the -3 series long-chain polyunsaturated fatty acid was distributed in the 1st and 3rd positions of the triglyceride. That is, 6.5 mol% of the total amount of the n-3 long-chain polyunsaturated fatty acid was distributed at the 2-position of this triglyceride. This triglyceride was used as a test oil for the following animal experiments.

Sodium methoxide (0.1% by weight) was added to a part of the triglyceride, and a random transesterification reaction was carried out at 100 ° C. under reduced pressure, followed by filtration through Celite to obtain a random transesterification product of the triglyceride. Got The total fatty acid composition, the respective fatty acid compositions at the 1st, 3rd and 2nd positions were determined in the same manner as described above (see Table 1). At the 2-position of this triglyceride, 50.6 mol% of the total amount of the n-3 long-chain polyunsaturated fatty acid was distributed. This random transesterification product was used as a control oil for animal experiments.

[0043]

[Table 1] * Total carbon number: Displayed as the number of double bonds. (N-3) represents an n-3 fatty acid.

Seven 4-week-old male SD rats were used as one test group, and a breeding experiment was carried out using a feed containing 5% by weight of each of the test oil and the control oil (see Table 2). During this period, the feed was prepared and fed daily in order to prevent oxidative deterioration of the feed components. After being allowed to freely ingest water and each of the above-mentioned feeds and bred for 3 weeks, neutral lipids in blood and liver of each test group rat,
The total cholesterol and phospholipid contents were measured.
Table 3 shows the results. At the same time, the amount of PGI _{2 in} the aorta and TXA _{2 in} the blood of each test group rat was measured. Table 4 shows the results. No significant difference was observed in feed intake, body weight gain and pancreas weight in each test group.

From the results of this experiment, the fats and oils consisting of the mixed triglyceride according to the present invention (test oil) had no side effect on rats, and in the group to which the test oil was added, blood triglyceride (neutral lipid) and total cholesterol were It became clear that the value and the value of triglyceride in the liver were remarkably reduced. In addition, in the group to which the fat or oil (test oil) composed of the mixed triglyceride according to the present invention was added, the production amount of PGI ₂ was remarkably increased (that is, the inhibitory action on the platelet aggregation ability and the arterial relaxation action were increased), and the TXA ₂ It was revealed that the production amount was extremely decreased (ie, the inducing action of platelet aggregation ability and the decrease of arterial contraction action). Therefore, it was confirmed that the fats and oils comprising the mixed triglyceride according to the present invention can be used for the prevention and treatment of hyperlipidemia and arteriosclerosis.

[0046]

[Table 2] * 1 Nippon Claire Co., Ltd., AIN-93G-MX * 2 Nippon Claire Co., Ltd., AIN-93-VX * 3 t-Butylhydroquinone

[0047]

[Table 3] * There is a significant difference with a risk rate of 5% or less with respect to the value of the control oil added section.

[0048]

[Table 4] *: Same as the notes in Table 3.

Reference Example 2 A test fat (fat containing the mixed triglyceride of the present invention) and a control fat were prepared as follows. That is, the test fats and oils were prepared by cooling harp seal fats and oils with a dry ice / acetone refrigerant at -80 ° C for 1 hour, and separating the precipitated crystal parts with a filter paper. The control fats and oils are two types of fish oils with different fatty acid composition (mixed oil of cod liver oil and miscellaneous fish oil, tuna orbital oil), cooled with dry ice / acetone refrigerant in the same manner, and the concentrated fractions are blended to obtain the total fatty acid composition. It is almost similar to that of the test fat. Table 5 shows these fatty acid compositions.

[0050]

[Table 5] *: Same as the notes in Table 1.

Seven 4-week-old SD male rats were used as one test group, and oils and fats containing 20% by weight of each of the above-mentioned test fats and control fats (test fats or control fats and oils, 20 parts by weight, palm oil 50 parts by weight, high A mixed fat containing 5 parts by weight of oleic safflower oil and 25 parts by weight of high linoleum safflower oil (see Table 6 for the fatty acid composition), each containing 10% by weight (the composition of the feed is 5% by weight of fat and 10% by weight). , The same as in Reference Example 1 except that 41.7% by weight of corn starch was changed to 36.7% by weight). During this time,
Feed was prepared and fed daily to prevent oxidative degradation of feed ingredients. After free feeding of water and each of the above-mentioned feeds and feeding for 3 weeks, the contents of neutral lipid, total cholesterol and phospholipid in blood and liver of each test group rat were measured in the same manner as in Reference Example 1 ( See Table 7). Similarly, the amounts of PGI _{2 in} the aorta and TXA ₂ in blood of each rat in each test group were measured (see Table 8). No significant difference was observed in feed intake, body weight gain, and liver weight in each test group.

From the results of this experiment, the fats and oils containing the mixed triglyceride according to the present invention (test fats and oils) had no adverse effect on rats, and the triglycerides (neutral lipids) and total cholesterol in blood and liver were It was found that the value was effectively reduced. In addition, it was revealed that in the group to which the test fat and oil was added, the PGI ₂ production amount was increased and the TXA ₂ production amount was decreased, that is, the inhibitory action on the platelet aggregation ability and the arterial vasodilatory action were enhanced. Therefore, it was confirmed that the fats and oils containing the mixed triglyceride according to the present invention can be used for the prevention and treatment of hyperlipidemia and arteriosclerosis.

[0053]

[Table 6] *: Same as the notes in Table 1. (N-6) shows an n-6 fatty acid. * *: Ratio of each fatty acid among saturated fatty acids, monounsaturated fatty acids, n-6 fatty acids and n-3 fatty acids.

[0054]

[Table 7] *: Same as the notes in Table 3.

[0055]

[Table 8] *: Same as the notes in Table 3.

Reference Example 3 A rat breeding experiment was carried out in the same manner as in Reference Example 2 by adding fats and oils having different mixing ratios of the test fats and control fats and oils used in Reference Example 2 to the feed. That is, 7 4-week-old male SD rats were used as one test group, and the fat or oil containing 10 wt% of the test fat or control fat or oil described in Reference Example 2 (10 wt parts of the test fat or control fat or oil, 50 parts by weight of palm oil) was added. , A mixed fat of 10 parts by weight of high oleic safflower oil and 30 parts by weight of high linoleum safflower oil. Refer to Table 9 for the fatty acid composition. The same as the above). During this time, the feed was prepared daily to prevent oxidative degradation of the feed components. After free feeding of water and each of the above-mentioned feeds and feeding for 3 weeks, the contents of neutral lipid, total cholesterol and phospholipid in blood and liver of each test group rat were measured in the same manner as in Reference Example 1 ( See Table 10). Similarly, the amounts of PGI _{2 in} the aorta and TXA _{2 in} the blood of each rat in each test group were measured (see Table 11). No significant difference was observed in feed intake, body weight gain and liver weight in each test group.

From the results of this experiment and the results of Reference Example 2,
The fats and oils containing the mixed triglyceride according to the present invention (test fats and oils) have no adverse effect on rats, and the fats and oils containing a small amount of the test fats and oils in comparison with the control fats and bloods and liver It was found to have the effect of significantly reducing the level of triglycerides (neutral lipids) therein. In addition, it was revealed that in the group to which the test fat and oil was added, the production amount of PGI ₂ was increased and the production amount of TXA ₂ was decreased, and the inhibitory action on the platelet aggregation ability and the dilation action on arterial blood vessels were enhanced. From this, it was confirmed that the fats and oils containing the mixed triglyceride according to the present invention can be used for the prevention and treatment of hyperlipidemia and arteriosclerosis.

[0058]

[Table 9] * And **: Same as the notes in Table 6.

[0059]

[Table 10] *: Same as the notes in Table 3.

[0060]

[Table 11] *: Same as the notes in Table 3.

Reference Example 4 Microalga Crypthecod
inium cohnii, ATCC 30336) was planted in 30 liters of the medium shown in Table 12, aerobically cultivated at 30 ° C. for 100 hours in a jar fermenter, and cultured alga cells were collected by centrifugation and frozen. It was dried (yield 625 g). The dried algal cells were crushed and extracted in a mixed solvent of chloroform: methanol = 1: 1 (weight ratio) with a hiscotron (trade name; manufactured by Nichine Medical Science Co., Ltd.) to obtain 520 g of an oil component. Silica gel dispersed in n-hexane (Wako Pure Chemical Industries, Ltd., trade name: Wakogel C
The oil was supplied to a stainless steel column filled with 100) and eluted with diethyl ether: n-hexane = 10: 90 (volume ratio) to obtain 250 g of the mixed triglyceride according to the present invention. The fatty acid composition of the present triglyceride (which was used as a test oil) was determined in the same manner as in Reference Example 1 (Table 1).
3).

[0062]

[Table 12] * 1: Vitamin mix aqueous solution (weight in 1 liter of the aqueous solution) Biotin: 0.003 g Thiamine: 1.000 g * 2: Metal mix aqueous solution (weight in 1 liter of the aqueous solution) Na ₂ EDTA: 1.00 g _{FeCl 3 · 6H 2 O: 0.05} g H 3 BO 3: 1.00 g MnCl 2 · 4H 2 O: 0.15 g ZnCl 2: 0.01 g CoCl 2 · 6H 2 O: 0.005g

[0063]

[Table 13] *: Same as the notes in Table 1.

The thus-obtained triglyceride derived from microalgae (test fat and oil) and the fat and oil containing 10 wt% of the fat and oil described in Reference Example 2 (10 wt parts of fat or oil for test or fat, 50 wt parts of palm oil, Hiole) 10 parts by weight of Ick safflower oil and 3 of high linoleum safflower oil
0 parts by weight of mixed fats and oils. See Table 14 for fatty acid composition)
A feed containing 0% by weight (the feed composition is the same as in Reference Example 3 except for fat content) was prepared, and the same breeding test as in Reference Example 3 was performed. Table 15 shows the analysis results of blood and liver lipid contents of each test group rat. Table 16 shows the results of analysis of the amount of PGI _{2 in} the aorta and the amount of TXA _{2 in} the blood of each test group rat. No significant difference was observed in feed intake, body weight gain and liver weight in each test plot.

From the results of this experiment and the results of Reference Example 2,
The fats and oils containing the mixed triglyceride according to the present invention (test fats and oils) have no adverse effect on rats, and the fats and oils containing a small amount of the test fats and oils in comparison with the control fats and bloods and liver It was found to have the effect of significantly reducing the levels of triglyceride (neutral lipid) and total cholesterol in the medium. In addition, it was revealed that in the group to which the test fat and oil was added, the production amount of PGI ₂ was increased and the production amount of TXA ₂ was decreased, and the inhibitory action on the platelet aggregation ability and the dilation action on arterial blood vessels were enhanced. From this, it was confirmed that the fats and oils containing the mixed triglyceride according to the present invention can be used for the prevention and treatment of hyperlipidemia and arteriosclerosis.

[0066]

[Table 14] * And **: Same as the notes in Table 6.

[0067]

[Table 15] *: Same as the notes in Table 3.

[0068]

[Table 16] *: Same as the notes in Table 3.

Example 1 Oils and fats according to the present invention prepared in Reference Examples 1 to 4 (Reference Example 1:
Test oil, Reference Example 2: Fats and oils containing 20 wt% of test fats and oils, Reference Examples 3 and 4: Fats and oils containing 10 wt% of test fats and oils, soybean lecithin (manufactured by Nisshin Oil Co., Ltd., product (Name: Basis LP-20. The same shall apply hereinafter.) 0.2 parts by weight and 10 parts by weight of egg white were mixed and stirred sufficiently, 180 parts by weight of warm milk was added, and the mixture was stirred for 2 minutes to obtain oil-containing milk. . These things have an energy of 148 Kcal,
Protein 6.6g, lipid 9.3g, sugar 8.7g,
As a result of evaluation by the flavor and 10 expert panels, it was a liquid food with no problem in flavor and appearance.

Example 2 1.5 parts by weight of any of the fats and oils according to the present invention prepared in Reference Examples 1 to 4 (see Example 1), 0.1 part by weight of soybean lecithin and 20 parts by weight of whole egg were well mixed. After that, 60 parts by weight of milk was added and further stirred sufficiently. This was poured into a small cup and steamed on a low heat for about 20 minutes to obtain a fat-containing pudding. These have an energy of 104 Kcal, protein 4.
The amount was 4 g, the lipid was 5.8 g, and the sugar was 8.1 g. As a result of evaluation in the same manner as in Example 1, the liquid food had no problem in flavor and appearance.

Example 3 20 parts by weight of any of the fats and oils according to the present invention (see Example 1) prepared in Reference Examples 1 to 4, medium-chain fatty acid triglyceride (manufactured by Nisshin Oil Co., Ltd., trade name: ODO) 10 parts by weight, egg white 10 parts by weight, casein (New Zealand Daily Board Co., trade name: Alacid) 10 parts by weight, dextrin (Matsuya Chemical Industry Co., Ltd., trade name: Glister P)
50 parts by weight and 100 parts by weight of water were sufficiently stirred to obtain a concentrated liquid food. These things have an energy of 519 Kcal,
The amount of protein was 9.6 g, the amount of lipid was 30.2 g, and the amount of sugar was 50.1 g. As a result of evaluation in the same manner as in Example 1, the liquid food had no problem in flavor and appearance.

Example 4 Oils and fats according to the present invention prepared in Reference Example 3 (see Example 1)
8 parts by weight, 83 parts by weight of corn starch, and 3 parts by weight of salt were mixed with lukewarm water and set on a fire, and when the precipitate disappeared and the mixture became white and gelatinized, the heat was turned off. After the temperature reached about 50 ° C, 6 parts by weight of diastase was added, and the mixture was left for a while. Furthermore, 44 parts by weight of shiratama powder was swollen with water, 44 parts by weight of skim milk, 35 parts by weight of sugar and 10 parts by weight of powdered vegetables were mixed and dissolved, and 22 parts by weight of beef liver and horse mackerel (grated into 3 pieces) 44 parts by weight) and boiled with soy sauce and well ground, were added, well mixed and boiled. This was cooled to a temperature of about human skin, 90 parts by weight of yogurt and 100 parts by weight of chicken egg were added and the mixture was lined to obtain 1 liter of a natural concentrated liquid food.
This product has an energy of 1228Kcal and a protein of 58.1.
g, lipids 25.1 g, and sugars 187.4 g, and the liquid food had no problem in flavor and appearance.

Example 5 Oil and fat according to the present invention prepared in Reference Example 1 (see Example 1)
13 parts by weight, soybean lecithin 0.8 parts by weight, skim milk / sugar = 2/1 (weight ratio) 96 parts by weight mixture and concentrated fruit juice 45 parts by weight were thoroughly stirred and boiled. This was cooled to a temperature of about human skin, 100 parts by weight of chicken egg was added and the mixture was lined to obtain 1 liter of a mixed concentrated liquid food. This product has energy 993 Kcal, protein 44.5 g, lipid 28.
The amount was 3 g and the sugar content was 140.9, and there was no problem in flavor and appearance. Also, in the same method and conditions as above, as the oil and fat, the oil and fat according to the present invention prepared in Reference Example 4 (see Example 1) was mixed, the mixed salad oil was mixed, and the control oil prepared in Reference Example 1 Was prepared, and an oil containing 10% by weight of the control oil described in Reference Example 4 was prepared.

These 5 kinds of liquid diets were used as test feeds, and 7 4-week-old SD male rats were used as 1 test group and 3
They were allowed to eat freely for a week. No significant difference was observed in feed intake, body weight gain and liver weight in each test group.
As a result of measuring the blood lipid concentration and the eicosanoid production amount in the same manner as in Reference Example 1, when the fats and oils according to the present invention were blended, the blood cholesterol level and the The blood triglyceride level was reduced to a large extent, the PGI ₂ production was large, and the TXA ₂ production was small.

Example 6 Fats and oils according to the present invention prepared in Reference Example 1 (see Example 1)
After 10 parts by weight and 1.2 parts by weight of soybean lecithin were stirred with a homogenizer at 12000 rpm for 15 minutes, 2.5 parts by weight of glycerin and 90 parts by weight of distilled water were added, and further stirred with a homogenizer at 20000 rpm for 20 minutes to pre-emulsify. The pre-emulsion was treated 5 times at a pressure of 638 psi with a French press (trade name, manufactured by Aminco Co.) to obtain a fat emulsion. The particle size of this fat emulsion was measured with a Coulter N4 counter (trade name, manufactured by Nikkaki Co., Ltd.) to be 200 ± 2.
It was 5 nm. This fat emulsion was placed at 4 ° C for 6 months and at room temperature for 6 months.
After storage for 1 month or more at 40 ° C. for 1 month or longer, the particle size measurement and the emulsified state were observed visually and under a polarizing microscope, but no change was observed and the good emulsified state was maintained. Further, a fat emulsifier was prepared in the same manner by using the control oil described in Reference Example 1 in place of the fat and oil.

Using the fat emulsion containing the control oil as a control, 5 4-week-old male SD rats were used as one test group, and 500 μl of each fat emulsion was administered via the tail vein, and then in the blood 4 hours later. As a result of measuring the lipid concentration and the amount of eicosanoid produced, when the fat emulsion containing the oil or fat according to the present invention was administered, the degree of reduction in blood cholesterol level and blood triglyceride level was larger than that in the control, and PGI ₂ production was increased. The amount was large and the amount of TXA ₂ produced was small.

Example 7 Oil and fat according to the present invention prepared in Reference Example 4 (see Example 1)
A fat emulsion was prepared by the method described in Example 6 using 10 parts by weight, egg yolk lecithin (manufactured by Funakoshi, reagent grade) 3.6 parts by weight, glycerin 30 parts by weight and distilled water 70 parts by weight. The particle size measured in the same manner as in the example is 63 ± 18 nm
Met. After storing this fat emulsion at 4 ° C for 6 months, at room temperature for 6 months, and at 40 ° C for 1 month or more, the particle size measurement and the emulsified state were observed visually and under a polarizing microscope, but no change was observed and a good emulsified state was observed. I kept it.

Using a fat emulsion prepared in the same manner with the fat containing 10% by weight of the control fat described in Reference Example 4 as a control, 5 4-week-old SD male rats were used as one test group, and the fat emulsion and physiology were adjusted. A mixture of saline and a weight ratio of 1: 1 was administered via the tail vein in an amount of 700 μl each, and the blood lipid concentration and eicosanoid production amount were measured 4 hours later. When the emulsion was administered, the degree of reduction in blood cholesterol level and blood triglyceride level was large, the PGI ₂ production amount was large, and the TXA ₂ production amount was small as compared with the control.

[0079]

EFFECTS OF THE INVENTION The medical oil / fat-containing composition of the present invention has no side effects on humans and animals, and is superior to the conventional n-3 long-chain polyunsaturated fatty acid source. Eicosanoid P is highly effective in lowering blood cholesterol level and / or blood triglyceride level.
The effect of increasing the GI ₂ production amount and decreasing the TXA ₂ production amount, that is, the effect of suppressing the platelet aggregation ability is large.
Therefore, the oil-and-fat-containing composition of the present invention has a conventional n-type composition such as fish oil.
-3 system long-chain polyunsaturated fatty acid can improve the lipid level in blood and suppress and regulate the aggregation of platelets by ingesting a smaller amount than those containing it, hyperlipidemia and arteriosclerosis It can be used for prevention and treatment of diseases.

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] August 12, 1996

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0007

[Correction method] Change

[Correction contents]

[0007] By the way, some of the raw materials used for ordinary meals contain ingredients that reduce the concentrations of blood cholesterol and blood triglyceride. For example, the soysterol is an unsaponifiable sterol contained in soybean, and JP-A-3-53866 discloses a lignan compound derived from sesame oil, and foods and drinks such as butter and mayonnaise containing the same are disclosed. Proposed. Eicosapentaenoic acid (C _{20: 5} , where the number after C represents the total number of carbons: the number of double bonds. The same applies hereinafter. All cis-5, 8, 11,
14,17-eicosapentaenoic acid, hereinafter abbreviated as EPA. ) And docosahexaenoic acid (C _{22: 6} , total cis-4,
7,10,13,16,19-docosahexaenoic acid,
Hereinafter abbreviated as DHA. It has been revealed from animal experiments and clinical experiments that n-3 long-chain polyunsaturated fatty acids and food materials containing them have the action of reducing serum cholesterol levels and triglyceride levels. For example , J. Dyerberg et al., Prog. Lipid Res., Volume 21, Vol.
55-269, 1982 ).

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0026

[Correction method] Change

[Correction contents]

The raw materials for the transesterification are vegetable oils such as linseed oil, sesame oil, perilla oil, etc. as component a-1, fish oils such as sardine oil, cod liver oil, herring oil, squid oil, tuna orbital oil, whales, seals, Compressed or extracted oil obtained from marine mammals such as fur seals, milk fat of the animals, chlorella, spirulina, donaliella , etc., and also genus Nannochloropsis (eg Nannochloropsis oculata , UTEX
LB 2164 etc. ), Trust chytrium (eg Thrausto
chytrium aureum , ATCC 28211, 34304 etc. ), Crypthecodinium cohnii , AT
CC 30021, 30334, 30336, 50052, etc. ), genus Isochrysis (for example, Isochrysis galbana , CCAP927 / 1, UTE
X LB 987, etc. ), oils and fats extracted from microalgae belonging to the genus Mortierella (M.is)
abellina, IFO 6336, 6739, 7873, 7884, ATCC 4
4853) or the like, or a triglyceride of an n-3 long-chain polyunsaturated fatty acid or a mixed fatty acid with the above-mentioned various fatty acids (see paragraph No. 0022) containing this at an arbitrary ratio. ATCC: American Type Cul
tureCollection (USA), CCAP: Culture Collection o
f Alage and Protozoa (UK), UTEX: Culture Collec
tion of Alage at the University of Texas (US
Country), IFO: Osaka Fermentation Research Institute. Ingredient a-2
As the above, various fatty acids or derivatives thereof described in paragraph 0022 can be used.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0044

[Correction method] Change

[Correction contents]

Seven 4-week-old SD male rats were used as one test group, and a breeding experiment was carried out using a feed containing 5% by weight of each of the test oil and the control oil (see Table 2). During this period, the feed was prepared and fed daily in order to prevent oxidative deterioration of the feed components. After allowing water and each of the above-mentioned feeds to be freely fed for 3 weeks, the content of neutral lipid, total cholesterol and phospholipid in blood and liver of each test group rat was measured. Table 3 shows the results. At the same time, the amount of PGI _{2 in} the aorta and TXA _{2 in} the blood of each test group rat was measured. Table 4 shows the results. No significant difference was observed in feed intake, body weight gain and pancreas weight in each test group.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0051

[Correction method] Change

[Correction contents]

Seven 4-week-old SD male rats were used as one test group, and the above-mentioned test fats and control fats and oils containing 20% by weight each (20 parts by weight of the test fats or control fats and 50 parts by weight of palm oil) were used. , A mixed fat of 5 parts by weight of high oleic safflower oil and 25 parts by weight of high linoleum safflower oil. Refer to Table 6 for the fatty acid composition. %, And the same as in Reference Example 1 except that 41.7% by weight of corn starch was changed to 36.7% by weight).
During this period, the feed was prepared and fed daily in order to prevent oxidative deterioration of the feed components. Free intake of water and each of the above feeds 3
After breeding for a week, the contents of neutral lipid, total cholesterol and phospholipid in blood and liver of each test group rat were measured in the same manner as in Reference Example 1 (see Table 7). Similarly, PGI ₂ of the aorta and TX in blood of each test group rat
Each amount of A ₂ was measured (see Table 8). No significant difference was observed in feed intake, body weight gain, and liver weight in each test group.

[Procedure Amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0064

[Correction method] Change

[Correction contents]

The triglyceride derived from microalgae thus obtained (test fat and oil) and the control fat and oil described in Reference Example 2 were used.
Used, the mixed oil and fat. The fatty acid composition of each 10 wt% including fat (test oils or control oil 10 parts by weight, palm oil 50 parts by weight, high-oleic safflower oil 10 parts by weight of high-linoleic safflower oil 30 parts by weight Table (See 14)
A feed containing 10% by weight of each of the above was prepared (the feed composition is the same as in Reference Example 3 except for fat content), and the same breeding test as in Reference Example 3 was performed. Table 15 shows the analysis results of blood and liver lipid contents of each test group rat. Table 16 shows the results of analysis of the amount of PGI _{2 in} the aorta and the amount of TXA _{2 in} the blood of each test group rat. No significant difference was observed in feed intake, body weight gain and liver weight in each test plot.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location C12R 1:89)

Claims (8)

[Claims] 1. An n-3 long-chain polyunsaturated fatty acid is contained as a constituent fatty acid of the glyceride, and less than 40 mol% of the total amount of the n-3 long-chain polyunsaturated fatty acid is bonded to the 2-position of the glyceride. A medical fat and oil-containing composition containing a fat and oil consisting of mixed triglycerides. 2. A medical fat-and-oil-containing composition containing an oil or fat containing 5% by weight or more of the mixed triglyceride according to claim 1. 3. The n-3 long-chain polyunsaturated fatty acid is one or more selected from the group consisting of α-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid. The medical fat and oil-containing composition according to claim 1 or 2. 4. The medical fat and oil-containing composition according to claim 1, wherein the n-3 long-chain polyunsaturated fatty acid is eicosapentaenoic acid and / or docosahexaenoic acid. 5. The medical use according to any one of claims 1 to 4, wherein the mixed triglyceride is obtained from marine mammals or microalgae, is concentrated, or is transesterified. Fat-containing composition. 6. The medical oil and fat-containing composition according to claim 5, wherein the marine mammal is a whale or a seal. 7. The oil-and-fat composition for medical use according to claim 5, wherein the microalgae belongs to the genus Nannochloropsis, the genus Trastochytrium, the genus Isochrysis, or the genus Crypthecodinium. 8. The mixed triglyceride is a glyceride 1,
It is produced by a transesterification reaction using a lipase having specificity at the 3-position.
The medical fat and oil-containing composition according to any one of 1.