JP2000355538A - Receptor agonist responsive to peroxisome activator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new receptor agonist responsive to peroxisome activator effective for the prophylactic or improvement of internal organ fat reduction, internal organ fat accumulation inhibition, lipid metabolism abnormality and anomaly of saccharometabolism, and effective for the prophylactic or therapy of cancer, in humans or animals. SOLUTION: This receptor agonist responsive to peroxisome activator is such one as to contain at least one kind selected from 10-26C conjugated unsaturated fatty acids each containing a conjugated triene structure (CH=CH-CH= CH-CH=CH) or a conjugated tetraene structure (CH=CH-CH=CH-CH=CH-CH =CH) in its molecule, salts thereof and ester derivatives thereof, facilitate the binding of the human or animal receptor agonist responsive to peroxisome activator to a target gene sequence, facilitate gene expression on the downstream side thereof, and provide prophylactic or improvement of internal organ fat reduction, internal organ fat accumulation inhibition, lipid metabolism abnormality and anomaly of saccharometabolism, and the prophylactic or therapy of cancer.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a peroxysome activator-responsive receptor (peroxysome proliferator-acti
vated receptor) (hereinafter abbreviated as PPAR) promotes binding to a target gene sequence and has an activity of promoting downstream gene expression (hereinafter abbreviated as PPAR agonist activity) (hereinafter referred to as PPAR agonist). Abbreviation), and reduction of visceral fat, suppression of visceral fat accumulation, improvement of lipid metabolism abnormality, improvement of glucose metabolism abnormality, or prevention and treatment of cancer by the PPAR agonist.

[0002]

2. Description of the Related Art With the advent of an aging society, there is a need for foods and drinks and pharmaceuticals that are effective in preventing and treating human lifestyle-related diseases represented by diabetes, arteriosclerosis, hypertension, hyperlipidemia, fatty liver, and cancer. Is increasing. Also, in pet animals, obesity,
Diabetes has become a problem today, and the development of feed and veterinary medicines that can prevent and treat these diseases is awaited. Recent advances in obesity research have revealed that obesity, particularly visceral fat accumulation obesity, is an important risk factor for lifestyle-related diseases (Takahashi et al., The 19th Annual Meeting of the Japanese Society for Obesity, p64 It is expected that these lifestyle-related diseases can be prevented or improved by improving visceral fat accumulation type obesity.

[0003] Adipose tissue, a major in vivo organ of visceral fat accumulation, has heretofore been understood as a mere place for storing excess fat. However, due to recent advances in adipocyte research, adipose tissue is not just a place for storing excess energy in the living body, but an organ that secretes various bioactive substances and functions actively in energy regulation. It has become clear. It is believed that PPAR, one of the nuclear receptors, plays a significant role in regulating the function of adipose tissue. PPAR is named for being activated by compounds of various structures having a proliferative action on peroxisomes, which are organelles (Issemann et. Al., Nat.
347, 645-650), and c-DNA has been cloned from various animal species and tissues, including humans. At present, three subtypes α, β, and γ are known, and PPARα, PPAR
PARβ (sometimes referred to as PPARδ or FAAR, NUC1) and PPARγ. PP
ARα is mainly expressed in hepatocytes, and PPARβ is expressed in heart, lung,
Common in the kidney, PPARγ is abundant in adipocytes. Each subtype of PPAR forms a heterodimer with retinoid X receptor (RXR) in common, binds to a PPAR response element upstream of the target gene, and exerts its function by regulating the transcription of the target gene. (Lemberge
al., Ann. Rev. Cell Dev. Biol., 12, 335-363,
1996). PPAR target genes include satiety factor leptin, lipoprotein lipase involved in fatty acid uptake, fatty acid transporter, fatty acid binding protein involved in fatty acid transport, malic enzyme involved in fatty acid synthesis, phosphoenolpyruvate carboxylate Genes such as kinases, acyl-CoA synthase involved in β-oxidation, acyl-CoA oxidase, keto-acyl-CoA thiolase, and unconjugated protein 1 (uncopling protein 1: UCP-) involved in heat production in brown adipose tissue.
1) and the like are known. Since all of these target gene products are important proteins that control fat metabolism, sugar metabolism, and energy metabolism in living organisms,
AR is considered to be an important protein that controls fat synthesis, decomposition and metabolism, sugar metabolism, and energy metabolism in vivo (Kawata, History of Medicine, 184, 519, 19).
98; Kawata, clinician, 23, 1300, 1997; Akira, History of Medicine, 184, 513, 1998). In particular, regarding PPARγ,
PPARγ on fibroblasts performed by Tontonz et al.
From the results of gene transfer / expression experiments, it has been proved that PPARγ is an important factor controlling adipocyte differentiation (Cell, 79, 1147-1156, 1994). Therefore, substances that exhibit PPAR agonist activity include, in addition to enhancing fat breakdown and metabolism, enhancing energy metabolism,
It is expected to reduce fat in the body, especially visceral fat, and improve lipid metabolism disorders (Kawata, History of Medicine,
184, 519, 1998; Kawata, clinician, 23, 1300, 1997; Akira, History of Medicine, 184, 513, 1998).

[0004] It is also known that thiazolidine derivatives, which are PPARγ agonists, remarkably improve glucose metabolism disorders represented by insulin resistance in type II diabetes patients. Although the mechanism is not fully understood, PPAR
As a result of the gamma agonist promoting adipocyte differentiation, it suppresses the production of TNFα, one of the causative substances of insulin resistance, and promotes the expression of glucose transporter (Glut4) in peripheral tissues to reduce free fatty acids. As a result, it is considered that the uptake of glucose into cells is enhanced and hyperglycemia is improved. (Kawata, Latest Medicine, 53, 402, 1998; Araki et al., History of Medicine, 188, 50)
0, 1999; JMLehmann et.al., J. Biol. Chem., 270, 12
953, 1995; T. Fujiwara et.al., Diabetes, 37, 1549,
1988). It has also been reported that PPAR agonists stop cell proliferation and promote cell differentiation (S. kita).
mura et.al., Jpn. J. Cancer Res., 90, 75, 1999).

[0005] The accumulation of visceral fat, abnormalities in lipid metabolism, and abnormalities in glucose metabolism include hyperlipidemia, diabetes, hypertension, arteriosclerosis,
It is well known that it is an important risk factor for lifestyle-related diseases such as fatty liver and heart disease. Therefore, substances that reduce these risk factors are promising as foods, drinks, pharmaceuticals, and feed compositions that have preventive and / or ameliorating effects for many lifestyle-related diseases (Mizukami et al., The Latest Medicine, 53, 402, 1).
998).

[0006] At present, a true PPAR agonist that performs physiological functions in vivo has not been identified, but PPAR has been identified.
Long chain fatty acids, leukotriene B4, clofibrate, and carbaprostacyclin are substances exhibiting α agonist activity, and long chain fatty acids, carbaprostacyclin,
As substances which show vesafibric acid and PPARγ agonist activity, thiazolidine derivatives (for example, troglidazone), 15-deoxy- △ ^12,14 -prostaglandin J ₂ , indomethacin, highly unsaturated fatty acids and the like are known. (Kawata, Latest Medicine, 53, 402, 1998; Kawada, History of Medicine, 184, 519, 1998; SAKliewer et.a
l., Proc. Natl. Acad. Sci. USA, 94, 4318, 1997). Recently, it has been reported that conjugated linoleic acid (hereinafter abbreviated as CLA) exhibits PPARα, β and γ agonist activity (KLHouseknecht, Biochem. Biop.
hys. Res. Comm., 244, 678, 1998; SYMoya-Camarena
et. al., Biochemica et Biophysica Acta, 1436, 33
1, 1999). As is clear from these reports, PPAR
It is widely recognized that the ligand selectivity between each of the subtypes is quite wide, and that a substance acting as an agonist of a specific subtype also shows activity against other subtypes,
This is one of the features of PPAR.

[0007] Among the substances exhibiting PPAR agonist activity,
A diet effect has been reported for fish oil containing CLA and high concentration docosahexaenoic acid (hereinafter abbreviated as DHA) (KLHouseknecht, Biochem. Biophys. Re.
s. Comm. 244,678,1998, JP-T10-508189, T.Ka
wada et.al., J. Agr. Food Chem., 46, 1225, 1998). C
LA is marketed as a health food under the trade name Tonalin® or Active Linol®, and DH
Fish oil with high A content is also commercially available as a health food material. However, neither CLA nor DHA-rich fish oil has an insufficient visceral fat-reducing effect or visceral fat accumulation-suppressing effect.
Safety concerns remain, including significant side effects such as hepatic enlargement at doses that are effective (DBWest et.a.
l., Am. J. Physiol., 275, R667, 1998). In addition, the CLA and DHA both have poor flavor and are used as health foods by methods such as encapsulation, but they are often used as compositions for general foods and drinks, pharmaceuticals, and feeds. The problem remains. In addition, both are expensive, and their use as compositions for general foods and feeds is limited. Therefore, safe, strong activity, flavor, excellent palatability, etc., economical, foods and beverages, medicines that exhibit a remarkable visceral fat reduction effect, visceral fat accumulation prevention effect,
The development of feed and feed compositions and their uses have been awaited.

Further, clofibrate is used as a drug for improving lipid metabolism disorders such as hyperlipidemia, and a thiazolidine derivative (for example, TZD) is used as a drug for treating type II diabetes having an effect of improving insulin resistance. There is a need for new compositions that are safe and effective.

On the other hand, it has been reported that cis-parinaric acid, one of conjugated tetraenoic acids, binds to PPARγ protein, but PPARγ agonist activity has not been confirmed (CNAPalmer, CRWolf, FEBSlett).
er 431, 476, 1998). In addition, cis-parinaric acid is known to exist only in a very limited amount of raw materials such as balsam seeds in nature, so that industrial use is difficult.

[0010]

As described above, DHA-rich fish oil and CLA have conventionally been known as fat compositions having PPAR agonist activity, but their visceral fat reducing effect is weak, and food and drink have been reduced. It has problems in flavor, taste, and economy as a product, and has not yet been generalized as a food or drink composition. In addition, clofibrate and thiazolidine derivatives are known as pharmaceutical compositions, but the effect of reducing visceral fat is not sufficient, and a more active and safe composition is required. Therefore, an object of the present invention is to have a strong PPAR agonist activity, show a visceral fat reducing effect, a visceral fat accumulation suppressing effect, a lipid metabolic disorder improving effect, a glucose metabolic disorder improving effect, an anticancer effect, and a safe PPAR agonist and An object of the present invention is to provide an oil / fat composition containing the same and foods / drinks, medicines and feeds containing the same as an active ingredient.

[0011]

Means for Solving the Problems The present inventors have been studying fats and oils related to foods for many years, and have particularly studied the mechanism of adipocyte differentiation, substances that induce differentiation and their functions. Was. In the course of these studies, P
A system for efficiently evaluating agonists of PPARγ, a typical subtype of PAR, was constructed, and the PPAR agonist activity of polyunsaturated fatty acids was evaluated using the evaluation system.
It was found to be much more active than conjugated dienoic acids such as A. Based on this knowledge, as a result of further intensive studies,
The present invention has been completed.

That is, the peroxisome activator-responsive receptor agonist according to the present invention contains, as an active ingredient, a conjugated triene structure (—CH ＝ CH—CH ＝ CH—C—C) in the molecule.
H = CH-) or a conjugated tetraene structure (-CH = CH-)
It contains at least one selected from conjugated unsaturated fatty acids having 10 to 26 carbon atoms having CH = CH-CH = CH-CH = CH-), salts thereof and ester derivatives thereof.

In a preferred embodiment of the peroxisome activator-responsive receptor agonist, a conjugated triene structure (—CH ＝ CH—
CH = CH-CH = CH-) having 10 to 26 carbon atoms
At least one selected from the group consisting of conjugated unsaturated fatty acids, salts thereof and ester derivatives thereof.

In a further preferred embodiment of the peroxisome activator-responsive receptor agonist, punicic acid, calendic acid, α-eleostearic acid, β-eleostearic acid, catalpic acid and At least one kind of conjugated unsaturated fatty acid selected from parinaric acid, a salt thereof, or an ester derivative thereof, particularly one containing at least one of ethyl ester and glycerol ester derivatives of the conjugated unsaturated fatty acid.

In another preferred embodiment, the peroxisome activator-responsive receptor is a peroxisome activator-responsive receptor agonist wherein the peroxisome activator-responsive receptor is peroxisome activator-responsive receptor γ.

The present invention is also an oil / fat composition containing the peroxisome activator-responsive receptor agonist as described above.

A preferred embodiment of the oil / fat composition comprises at least one plant seed selected from plants belonging to the family Pomegranate, Pterodaceae, Papilionaceae, Uriaceae, Plumbaceae, and Scapeaceae Or a processed product thereof.

[0018] In a further preferred embodiment of the oil / fat composition, the plant seed extract is preferably at least one selected from pomegranate seed oil, calendula seed oil, tung oil, bitter gourd seed oil, catalpa seed oil, and balsam seed oil. Is a seed.

The second aspect of the present invention is a drug containing the above-mentioned peroxisome activator-responsive receptor agonist as an active ingredient. Preferred embodiments of the medicament are a visceral fat reducing and visceral fat accumulation inhibitor, a lipid metabolism disorder preventing and improving agent, a glucose metabolism disorder preventing and improving agent, and a cancer preventing and treating agent.

A third aspect of the present invention is a food or drink containing the peroxisome activator-responsive receptor agonist. Preferred embodiments of the food and drink include margarine, shortening, edible oil, dressing, mayonnaise, chocolate, cookies, pies, and bread.

A fourth aspect of the present invention is a feed containing the peroxisome activator-responsive receptor agonist.

[0022]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. The PPAR agonist of the present invention and the fat composition containing the same are important factors at the top of a series of gene cascades related to the differentiation of fat cells, regulation of fat synthesis / accumulation / metabolism / degradation and sugar metabolism, and thermogenesis Shows an agonistic activity against PPAR. The PPAR agonist activity of the PPAR agonist and the oil / fat composition of the present invention can be measured by an efficient method newly developed by the present inventors. That is, GAL4 (a yeast DN) and a ligand binding site of PPARγ expressed specifically in adipocytes.
A plasmid (pM-PPAR) that produces a chimeric protein at the DNA binding site of the A-binding transcription factor activator;
Alternatively, a plasmid (pM) obtained by removing the PPARγ gene from pM-PPAR, and a GAL4 response element (USAg) upstream of the luciferase gene which is a reporter gene
(4 × UASg-1)
uc) was cultured in African green monkey kidney-derived cultured cells (C
V-1) by co-transfection by the lipofection method (Kazuaki Yoshikawa, Gene Transfer Expression Research for Neurophysiology, Springer Verlag Tokyo, 1997),
After culturing the obtained transformant for a certain period of time, it is treated with an agonist candidate substance, whereby PPARγ-G
Activating the AL4 chimeric protein, 4 × UASg-1
It enhances binding to USAg upstream of uc, thereby increasing luciferase production. The agonist activity can be evaluated by measuring the activity of the produced luciferase (Picagene luminescence kit instruction manual, Toyo B-Net).

The effect of reducing the visceral fat or inhibiting the accumulation of visceral fat by the PPAR agonist and the oil / fat composition of the present invention can be obtained by adding a candidate compound to an experimental animal for a certain period of time (for example, 4 weeks).
After the administration, evaluation is performed by quantifying the amount of visceral fat such as peritesticular adipose tissue and perirenal adipose tissue.

The PPAR agonist used in the practice of the present invention may exhibit an agonistic activity for any of the PPAR subtypes due to the extremely wide ligand selectivity of the PPAR. Judging from the specificity, it is more desirable to exhibit an agonist activity for PPARγ. The PPAR agonist of the present invention has a conjugated triene structure (-CH = CH-CH = CH-C) as an active ingredient exhibiting agonist activity.
H = CH-) or a conjugated tetraene structure (-CH = CH-)
It contains at least one or more conjugated unsaturated fatty acids having 10 to 26 carbon atoms having CH = CH-CH = CH-CH = CH-), salts and ester derivatives thereof. These conjugated unsaturated fatty acids are not particularly limited as long as they exhibit PPAR agonist activity, and may have an unsaturated bond in a portion other than the conjugated triene structure or conjugated tetraene structure, or may be substituted with another atom. Although it may be acceptable, food-, nutrition-, physiological-, and pharmacologically-acceptable ones are preferable.

Specific examples of the active ingredient exhibiting the agonist activity include punicic acid (18: 3,
9c, 11t, 13c), calendic acid
cid) (18: 3, 8t, 10t, 12c), jarcaric acid (18: 3, 8c, 10c)
t, 12c), α-eleostearic acid (α-eleostealic
acid) (18: 3, 9c, 11t, 13t), β-eleostealic acid (18: 3,9)
t, 11t, 13t), catalpic aci
d) (18: 3, 9t, 11t, 13c), kamlolenic acid (18OH, 9c, 11t,
13t) and other conjugated octadecatrienoic acids, conjugated fatty acids of eicosatetraenoic acid, and parinaric acid (18: 4, 9), which is a conjugated tetraenoic acid
c, 11t, 13t, 15c) and the like. In terms of stability and availability, a fatty acid having 18 carbon atoms having a conjugated triene structure is preferable.
In terms of agonist activity, the stereoisomer is 9-cis, 11
-Trans, 13-cis punicic acid, 9-cis, 11-t
rans, α-eleostearic acid which is 13-trans, 9
-Trans, 11-trans, 13-cis catalpic acid; 8-trans, 10-trans, 12-cis calendic acid, more preferably punicic acid and α
-Eleostearic acid.

The conjugated unsaturated fatty acid as an active ingredient of the PPAR agonist of the present invention may be in the form of a salt thereof or an ester derivative thereof. The salt is not particularly limited as long as it is food, nutritional, or pharmacologically acceptable. Metal salts such as sodium salt and calcium salt, ammonium salt, methylamine, ethylamine, diethylamine, triethylamine And salts with organic bases such as pyrrolidine, piperidine, piperidine, morpholine, hexamethyleneimine, aniline and pyridine, and salts with amino acids such as arginine, glutamic acid and ornithine. Further, as the ester derivative, any food-, nutritional-, or pharmacologically-acceptable one can be selected, but ethyl ester, butyl ester, propyl ester, and glycerol ester are preferable, and more preferably. Are ethyl esters and glycerol esters. The glycerol ester derivative may be in any form of monoglyceride, diglyceride, and triglyceride, preferably in the form of diglyceride and triglyceride, and most preferably in triglyceride. In these diglycerides and triglycerides, the position where the conjugated unsaturated fatty acid is esterified may be selected according to the purpose, and is not particularly limited. Specific conjugated unsaturated fatty acid ester derivatives include ethyl punicate, ethyl calendate, ethyl jarcaricate, ethyl α-eleostearate, ethyl β-eleostearate, ethyl catalpinate, ethyl parinarate, punicate Butyl, propyl punicate, 1
-Puniseal-sn-glycerol (1-punicyl-sn-gl
ycerol), 2-punisil-sn-glycerol (2-p
unicyl-sn-glycerol), 1,2-dipniseal-sn-
Glycerol (1,2-dipunicyl-sn-glycerol), 2,
3-dipunisil-sn-glycerol (2,3-dipun
icyl-sn-glycerol), 1,2,3-trypnicile-s
n-glycerol (1,3-tripunicyl-sn-glycero
l) and the like.

As the oil / fat composition having PPAR activity of the present invention, an oil / fat which is an extract of natural animals and plants can be used. The natural animal and vegetable fats and oils may be any of vegetable fats and oils, animal fats and oils, and marine fats and oils, but vegetable fats and oils, which are easy to secure in quantity, are preferred, and vegetable seed oils are more preferred. As these animal and plant fats and oils, general oils and fats commercially available for industrial use, food use or pharmaceutical use may be used, or natural animals and plants, preferably plant seeds may be extracted by a known method. The plant seed as a raw material is not particularly limited as long as it contains a conjugated unsaturated fatty acid having a PPAR activity, a salt thereof, or a derivative thereof, but the pomegranate family (Punicaceae) and the kiku family (Compositae family)
(Asteraceae)), Euphordiaceae (Euphordiaceae),
Cucuritaceae, Cucuritaceae, Bignonia
ceae) and plant seeds belonging to the family Balsaminaceae (Balsaminaceae), more preferably Pomegranate Pomegranate (P. granatum L.), Pomegranate (C. officinalis L.) Rabbit family Aburagiri genus Aburiri (A.cordata Mubll.Arg), Rubiaceae bitter gourd genus (Migacharantia L.),
Cattle genus cattle (C. ovata G. Do
n), squirrel and swelling family
samina L.).

In the present invention, the above-mentioned natural animal and vegetable fats and oils can be used as they are, or may be used after being processed into fatty acids or derivatives thereof. How to process into fatty acids,
It is preferable to pretreat the animal and vegetable oils and fats if necessary, hydrolyze them to obtain fatty acids, and purify them. As a pretreatment method of fats and oils, a physical method such as leaving a substance at a temperature higher than the melting point to settle and remove a substance having a large specific gravity, centrifuging and removing a substance having a small specific gravity, or adding sulfuric acid or phosphoric acid to a raw material fat or oil. In addition, heat and stir to decompose proteins and organic dyes, neutralize and remove by washing, or add activated clay and heat-treat to decompose products, coloring substances,
Chemical methods such as adsorption and removal of resinous substances and the like can be mentioned. Specific examples of hydrolysis include a method of saponifying fats and oils with an alkali such as potassium hydroxide, and a medium pressure catalytic decomposition method in which zinc oxide, calcium oxide, or magnesium oxide is decomposed under medium pressure conditions. Or a chemical method such as a continuous high-pressure digestion method of continuously decomposing under high pressure, and a biological hydrolysis method using lipase or a microorganism. As a method for separating and purifying fatty acids, a batch method, a semi-continuous method, a continuous distillation apparatus, or a method of purifying and purifying a target fatty acid using a precision distillation apparatus, a supersaturated solution or a melt to a target fatty acid. The mixture is cooled to an appropriate temperature to produce crystals, and the produced crystals are subjected to a squeezing method, a Solexol method (U.S. Pat.
2), Emersol method (US Pat. No. 2,421,157, 197)
4), Henkel method (W. Stein et al., J. Am. Oil Ch.
em. Soc., 45, 471, 1968).

The conjugated unsaturated fatty acid, which is an active ingredient of the PPAR agonist of the present invention, is prepared by culturing microorganisms such as algae, extracting oils and fats from the culture, and obtaining fatty acids by a known method. Is also good. Further, it may be prepared by reacting a known unsaturated fatty acid in the presence of a chemical catalyst or using a microorganism, an animal cell or an enzyme extracted therefrom. For example, red seaweed Ptilota filicina
A method for obtaining a highly conjugated unsaturated fatty acid having a conjugated triene structure from arachidonic acid, γ-linolenic acid, or eicosapentaenoic acid by using isomerase produced by MLWise, Biochemistry, 33, 15223, 1994.

In the present invention, the method for converting a conjugated unsaturated fatty acid into an ester derivative is not particularly limited. For example, a direct esterification method of synthesizing the fatty acid with an alcohol such as ethyl alcohol or glycerol by a dehydration reaction, an ester and an alcohol, A transesterification method of synthesizing a new ester by the reaction of an ester with the fatty acid or an ester with the ester, a method of synthesizing the fatty acid with a chloride and an alcohol, a method of reacting the epoxy compound with the fatty acid, a reaction of the olefin with the fatty acid A known method such as a method can be used, but a direct esterification method and a transesterification method are preferable. As a specific example of the direct esterification method, the fatty acid is mixed with an alcohol, and an azeotropic dehydrating agent such as toluene or xylene is added as necessary, and sulfuric acid, p-toluenesulfonic acid, zinc oxide, activated aluminum, oxide A method of heating in the presence of a catalyst such as titanium or tetraisopropyl titanate is exemplified. Further, specific examples of the transesterification method include an exchange reaction between a fatty acid ester and another fatty acid ester (Konoyoshi Hirao, Oil and Fat Chemistry, latter part, p522, Kazama Shobo, 1950), a reaction between a fatty acid ester and an alcohol (HJWright et al. Oil & Soap, 21, 145, 1944), ATGros & ROFeuge et al.
Am. Oil. Chem., 26, 704, 1949).

The fat and oil composition having PPAR activity of the present invention can be used as it is or as a food or drink by appropriately mixing it. Further, they can also be used as raw materials and processed food materials of various foods and drinks produced industrially. The content of the fat or oil composition in food or drink is not particularly limited, but is preferably 0.01 to 99% by weight,
More preferably, the content is 0.1 to 90% by weight. In addition, various carriers and / or additives acceptable as foods and drinks can be added and blended as desired. Any carrier or additive may be used as long as it does not adversely affect the PPAR agonist activity of the oil composition. Specific examples of such carriers include various carrier carriers, extenders, diluents, extenders, dispersants, excipients such as glucose and lactose, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP) and the like. Binders, solvents such as water, ethanol, vegetable oils, solubilizers, buffers such as baking soda,
Dissolution promoter, sodium CMC, HPMC, agar,
Gelling agents such as gelatin, and suspending agents such as sodium CMC and sodium alginate. Also, specific examples of additives include glutamine soda, edible ingredients such as inosinic acid, seasonings for improving palatability, vanilla,
Mints, rosemary, linalool, flavors such as natural flavors, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin E, vitamins such as pantothenic acid and nicotinic acid, sweeteners such as stevia, citric acid, Organic acids such as malic acid, fumaric acid, malonic acid, succinic acid, tartaric acid and lactic acid, coloring agents, moisture inhibitors, fibers, electrolytes, minerals, nutrients, antioxidants, preservatives, fragrances, humectants, tea extraction , Coffee extract, cocoa extract, orange, grape, apple, peach, pineapple, pear, plum, cherry, papaya, tomato, melon, strawberry, raspberry and other natural plant extracts.

The food or drink containing the oil or fat composition of the present invention may be any food or drink as long as it does not adversely affect the PPAR agonist activity of the oil or fat composition. Specifically, coffee, black tea, green tea, oolong tea Tea beverages such as
Fruit and vegetable drinks such as soy milk, green juice, fruit juice, vegetable juice, lactic acid bacteria drinks such as yogurt, milk drinks such as milk, carbonated drinks such as cola, and various sports drinks, as well as breads Bakery products, cooked rice, noodles, processed soybeans such as tofu, processed fish and meat foods such as sausage and ham, cakes, cookies, buns, crackers, ice cream, pudding, yokan, candy, chocolate and other confectionery, butter, Dairy products such as yogurt and cheese, processed fats and oils foods such as margarine and shortening, seasonings such as mayonnaise, dressing, soy sauce, miso and sauces, konjac, pickles and the like.

The food or drink containing the oil or fat composition of the present invention can be used as a food or drink having an effect of maintaining health, promoting health and enhancing physical strength. Specifically, improvement or suppression of obesity condition, reduction of accumulated fat, especially visceral fat,
Suppression of fat accumulation, especially suppression of visceral fat accumulation, improvement of abnormal lipid metabolism such as hyperlipidemia and hypercholesterolemia,
Improvement of glucose metabolism abnormalities such as diabetes tendency and postprandial hyperglycemia tendency,
It can be used as a food that exerts effects such as improvement of hypertension tendency and suppression of arterial intimal hypertrophy, or as a therapeutic food at the time of cancer treatment.

When the oil / fat composition having a PPAR agonist activity of the present invention is used as an active ingredient of a pharmaceutical, it is used as it is or in a pharmaceutically acceptable nontoxic and inert carrier in an amount of 0.01 to 99.5% by weight. %, Preferably 0.1 to
90% by weight and administered to mammals including humans. The dose of the drug to humans and other mammals is
The oil and fat composition can be appropriately selected depending on the purpose, as long as the desired effect is exhibited and the toxicity is not in the range where the toxicity is not recognized. However, the effective amount of the oil and fat composition is within the range of 1 mg to 3 g per 1 kg of the animal body weight. The amount may be administered once or several times a day. The precise dose of the drug can vary widely depending on the mode of administration, dosage form of the drug to be administered, the condition and weight of the subject to be treated, and is determined by the experience and choice of the responsible physician or veterinarian. Preferably. In addition, as the carrier, solid, semi-solid, liquid pharmaceutical preparations can be used in the usual production of carriers, and is not particularly limited, excipients such as glucose and lactose, starch, carboxymethylcellulose Disintegrators such as calcium (CMC-Ca), binders such as hydroxypropylcellulose (HPC) and polyvinylpyrrolidone (PVP), lubricants such as talc and magnesium stearate, pH regulators such as sodium bicarbonate, stabilizers,
One or more of diluents, dyes and the like, and other prescription auxiliaries are used. In general, it is preferable that the medicament is administered in a dosage unit form, and the medicament of the present invention is a tablet, a capsule,
It can be used as an oral preparation such as granules, powders, powders, dragees, suspensions, liquids, syrups, drops, sublingual tablets, emulsifiers, etc., or as a parenteral preparation such as injections and suppositories. If long-term administration is required, oral administration is preferred.

Pharmaceuticals containing the oil / fat composition of the present invention include antiobesity agents, visceral fat reducing agents, visceral fat accumulation inhibitors,
It can be used as a therapeutic agent for hyperlipidemia, a therapeutic agent for hypercholesterolemia, a therapeutic agent for diabetes, an insulin sensitizer, a therapeutic agent for hypertension, an anti-atherosclerotic agent, and a prophylactic / therapeutic agent for cancer.

The oil or fat composition of the present invention can be used as a feed as it is or by appropriately mixing seasonings, flavors and the like for improving edibility and palatability. At this time, an emulsifier and a stabilizer may be blended to maintain certain physical properties. Further, they can also be used as raw materials for various processed feeds and pet foods produced industrially. Moreover, you may sprinkle the fats-and-oils composition of this invention directly on feed and use it. The content of the oil and fat composition of the present invention in the feed is not particularly limited, but is, for example, 0.1 to 99.5% by weight, preferably 0.5% to 9% in terms of solid content with respect to the feed.
The range is 0% by weight.

The feed containing the oil and fat composition of the present invention can be used as a feed for preventing and improving obesity, a feed for preventing and treating diabetes, and a feed for preventing and treating cancer in livestock and pets.

When the oil and fat composition of the present invention is used in foods and drinks, pharmaceuticals and feeds, it may be used in combination with other foods and drinks, pharmaceuticals and feeds having similar effects.

[0039]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Conjugated Unsaturation from Plant Seeds
Preparation of fatty acid glycerol esters and conjugated unsaturated fatty acids
Pomegranate purchased from manufacturing community of fruit shop (the United States, California production) Divide the fruit of, the berries were removed in the around the seed in,
Dried pomegranate seeds, calendula seeds purchased from a seed distributor in the city, bitter melon seeds and balsam pear seeds, and catalpa seeds purchased from a Chinese herb shop in the city were crushed, and twice the weight of n-hexane was added. 6 hours in 2
The extraction was performed once and each extract was obtained. The solvent was distilled off from each extract to obtain pomegranate seed oil, calendula seed oil, bitter melon seed oil and catalpa seed oil. A hexane solution of the obtained various oils and a commercially available tung oil (Nacalai Tesque, Inc.) was applied to a silica gel 60F254 TLC plate (EM).
erck), developed with n-hexane: ethyl ether: acetic acid (60: 40: 1), and developed with iodine. Rf 0.5 to 0.
By 7 a major spot corresponding to triglycerides was observed. After dissolving 1 g of each of the plant seed oil and tung oil obtained as described above in ethanol, KOH was added thereto and hydrolyzed by heating. After extracting and removing unsaponifiables from the decomposition products,
The aqueous phase was separated, adjusted to pH 2.5, extracted with n-hexane, and the solvent was distilled off under reduced pressure to obtain a free fatty acid. As a result of TLC analysis of each fatty acid fraction in the same manner as described above, the main component was free fatty acids. The obtained free fatty acid was applied to silica gel column chromatography (Wakogel C-200, manufactured by Wako Pure Chemical Industries, Ltd.), washed with n-hexane, and eluted with n-hexane containing 20% by volume of ethyl ether to purify. A fatty acid fraction was obtained. The yield is 0.88 g from pomegranate seed oil, 0.91 g from calendula seed oil, 0.92 g from tung oil, 0.90 g from bitter melon seed oil, 0.90 g from catalpa seed oil, 0.8 from grape seed oil.
9 g.

Each of the fatty acids obtained as described above and a commercially available CLA (manufactured by Kenko Tsusho) are treated with a sulfuric acid-methanol solution (2: 230, volume ratio) in the presence of dimethyl sulfoxide. The fatty acid methyl ester derivative was analyzed by gas chromatography under the following conditions.

System: HP (Hewlett-Packer) 5890 Series II. Column: SPELUCO SP-2380, 100mm x 0.2
5mmID. Column temperature: 185 ° C. Injection temperature: 200 ° C. Detector temperature: 210 ° C.

Further, each fatty acid was added to each fatty acid by the method of Takagi (Takagi, Nippon Kagaku Magazine, 86, 296, 1965).
g to ethanol 60ml and hydrazine hydrate 10m
The reaction mixture was stirred for 2 hours while blowing air at 50 ° C., and the reaction product was extracted with diethyl ether. The extract was washed with an aqueous hydrochloric acid solution, and ether was distilled off. 10 ml of 2% sulfuric acid-methanol was added to the product, and the mixture was left overnight under nitrogen to obtain a methyl ester. The obtained product was analyzed by silver nitrate immersion silica gel thin film chromatography. In addition, lead to dimethyl disulfide adduct, GC
/ MS (ThermoQuest GC-9).

Based on the results of the analysis, the number of carbon atoms, the number of unsaturated bonds, the position of the unsaturated bonds, and the stereoisomerism of the obtained fatty acid were determined. The results of the analysis are summarized in Table 1.

[0045]

[Table 1]

As a result, the main component of the fatty acid derived from pomegranate seed oil was punicic acid. The main components of calendula seed oil-derived fatty acids were calendic acid and linoleic acid. The main component of tung oil and bitter gourd seed oil-derived fatty acid was α-eleostearic acid. The main components of catalpa seed oil-derived fatty acids were catalpic acid and linoleic acid. The main component of the fatty acid derived from Balsam seed oil was parinaric acid.

Example 2 P of fatty acid derived from vegetable seed oil
PAR agonist activity CV-1 (cultured cells derived from male African green monkey kidney, purchased from Human Science Corporation)
2 × 10 ⁴ cells were treated with 10% fetal bovine serum (GIBCO) and penicillin / streptomycin (10
000 units / ml, 10,000 μg / ml, GIBCO
DMEM (Dulbecco's Modified) containing ascorbic acid (37 μg / ml, manufactured by Wako Pure Chemical Industries, Ltd.)
2 containing 500 μl of Eagle medium (GIBCO)
The cells were inoculated in a 4-well plate, cultured at 37 ° C. under 5% CO ₂ for 24 hours, and OPTI-MEM (GIBCO).
PM-PPAR previously prepared and stored according to the method of Yoshikawa (Kazuaki Yoshikawa, Gene Transfer Expression Research for Neurophysiology, Springer Verlag Tokyo, 1997)
[The yeast-derived transcription factor GA is contained in the pSV40 expression vector.
PSV4 containing L4 gene (amino acid sequence 1-147)
And a chimeric protein expression plasmid prepared by inserting a PPARγ ligand binding site gene (amino acid sequence 204-505) at the C-terminal side of GAL4 in an expression vector] and 4 × U
ASg-luc [GAL4 response element (UASg) is located upstream of the luciferase gene as a reporter gene.
Reporter Presmid] or PM
(Plasmid from which the PPARγ ligand binding site sequence was removed from the PM-PPAR), and 4 × UASg-lu
c to Lipofect AMINE (GIBCO)
5 hours after the completion of transfection, DMEM containing 20% fetal calf serum was added, the serum concentration was adjusted to 10%, and the cells were cultured overnight. The next morning, as a ligand reagent addition group, conjugated linoleic acid (CLA, purchased from Kenko Tsusho Co., Ltd.) and Example 1
Each hexane solution of a pomegranate seed oil-derived fatty acid, a calendula seed oil-derived fatty acid, a tung oil-derived fatty acid, a catalpa seed oil-derived fatty acid, a bitter gourd seed oil-derived fatty acid, and a balsam seed oil-derived fatty acid prepared in the same manner as above is dried under a nitrogen stream. After the up, a group was prepared in which the medium was dissolved in dimethylsulfoxide (DMSO) and exchanged with a medium prepared by diluting 1000-fold with DMEM containing 10% activated carbon-treated fetal bovine serum (final fatty acid concentration: 20 μM). In addition, as an untreated control group, a group was prepared in which only DMSO was replaced with a medium diluted with DMEM containing 10% activated carbon-treated fetal calf serum. Further, as a positive control group, troglidazone (manufactured by Sankyo Co., Ltd .; hereinafter, abbreviated as TZD) (1 μM), which is conventionally known to be a strong agonist of PPARγ.
A group replaced with a medium containing was prepared. One day after medium exchange, the medium was removed and the cells were washed with phosphate buffered saline (PB
After washing with S), a cell lysate is prepared using Picker Gene cell lysate Luc (manufactured by Toyo Ink Co., Ltd.), and 20 μl of the cell lysate is reacted with 100 μl of Picker Gene luminescent substrate (manufactured by Toyo Ink Co., Ltd.) Luminometer (Berthold Lumat LB9) with a measurement time of 10 seconds
501) was used to measure luciferase activity.

The obtained results were analyzed as follows.
That is, in the untreated control group, the measurement group (pM-PPAR
The ratio of the control group (the group transfected with pM and 4 × UASg-luc) to the control group (the group transfected with 4 × UASg-luc) was defined as (a). Is defined as (b), and the PPARγ agonist activity by the ligand reagent was evaluated by the ratio of (b) / (a). To avoid errors due to differences in transfection efficiency between tests, TZD (1 μM) was added as a positive control group to correct values between tests.

[0049]

[Table 2]

As shown in Table 2, in the group to which the fatty acid derived from plant seeds containing conjugated trienoic acid as a main component was added, the PPAR agonist activity stronger than that of CLA was observed. Fatty acids other than conjugated trienoic acid contained in each fatty acid fraction do not show a strong PPAR agonist activity superior to CLA.
It is clear that it has R agonist activity.

(Example 3) Fatty acids derived from pomegranate seed oil
PPAR agonist activity of CLA and CLA In the same manner as in Example 2, the concentrations of CLA and pomegranate seed oil-derived fatty acids were changed, and their PPAR agonist activities were evaluated. As a result, as shown in Table 3, the pomegranate seed-derived fatty acid showed almost the same PPARγ agonist activity at about 1/10 concentration of CLA, and at a concentration of 57 μM or more, TZD
(1 μM).

[0052]

[Table 3]

Example 4 Low Visceral Fat of Pomegranate Seed Oil
Reducing effect, female C57BL / 6J mice improving lipid metabolism 10 weeks old (manufactured by CLEA Japan, Inc.), reared for 3 weeks on a high fat and high sugar diet purified diet showing the composition in Table 4 (manufactured Oriental Yeast Co., Ltd.) After obesity was obtained, the animals were divided into 8 animals / group and subjected to test with 2% by weight of soybean oil as an essential fatty acid source in a standard mixed feed for growth period (AIN-93G: manufactured by Oriental Yeast Co., Ltd.) from which fat was removed. The animals were reared for 3 weeks on a test feed to which 7% by weight of fat or oil or 7% by weight of control fat or oil was added. Three weeks later, after feeding the last food, fasting for 16 hours, whole blood was collected using a syringe containing heparin under ether anesthesia, and then dissected, followed by perirenal adipose tissue, periovary adipose tissue, Liver, kidney and spleen were collected and their weight was measured. The obtained organ weight was divided by the body weight to determine the organ weight ratio to the body weight. Peri-renal adipose tissue and peri-ovarian adipose tissue were evaluated as visceral adipose tissue. The collected blood was cooled to 3000
After spinning for 15 minutes to obtain plasma, total cholesterol concentration is released by cholesterol C-test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) and neutral fat concentration is released by triglyceride G-test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) The fatty acid concentration was measured by NEFA C Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). As a test group, a group added with pomegranate seed oil prepared by the same method as in Example 1 (pomegranate seed oil group), as a control group, a group added with soybean oil (soybean oil group), and as a comparative group, A group (fish oil group) to which a DHA-rich fish oil (having a DHA content of 20% by weight) (manufactured by Harima Chemicals, Inc.), which is known to have an obesity improving effect, was added. Further, as a CLA group, a group (CLA group) to which 6.5% by weight of soybean oil and 0.5% by weight of CLA (manufactured by Kenko Tsusho Co., Ltd., 70% purity) were added was provided. As a result of the preliminary test, under the same test conditions, when CLA was added at 1% by weight or more, remarkable hepatic hypertrophy (1.4 times that of the control) and a decrease in food consumption were observed. The appropriate dose was determined to be 0.5% by weight or less, and was set to 0.5% by weight. On the other hand, a group (standard diet group, n = 3) was provided from the beginning to eat a standard diet containing 9% by weight of soybean oil throughout the test period. During the test period, water was freely ingested, and the diet was restricted to the same level as the soybean oil group.

[0054]

[Table 4]

As a result, as shown in Table 5, during the test period,
There were no significant changes in food intake or body weight gain between each group. The weight ratio of visceral fat to body weight was clearly increased in the soybean oil group as compared to the standard diet group, suggesting that the mice exhibited visceral fat obesity by ingesting a high fat / high sugar diet. When the weight ratio of visceral fat to body weight of each group was compared, in the order of fish oil group> soybean oil group> CLA group> pomegranate seed oil group, pomegranate seed oil clearly showed a visceral fat reducing effect superior to fish oil and CLA.

[0056]

[Table 5]

As a result of analyzing the plasma total cholesterol concentration, neutral fat concentration, and free fatty acid concentration, as shown in Table 6, the pomegranate seed oil group showed a tendency to reduce neutral fat and a significant effect of reducing free fatty acids. As a result, an effect of improving lipid metabolism in the living body was observed.

[0058]

[Table 6]

(Example 5) Visceral fat storage of pomegranate seed oil
Of product inhibitory effect 6 week old female ICR strain CD-1 mice (manufactured by Charles River Co.) were divided into 8 mice / group, mice, rat standard mixed feed removing the fat (anagen for AIN-93G,
Oriental Yeast Co., Ltd.) was fed for 4 weeks using a feed prepared by adding a predetermined amount of the test oil and fat. Four weeks later, the animals were dissected under ether anesthesia, and the peri-renal adipose tissue, the peri-ovarian adipose tissue, the liver, the kidney, and the spleen were collected and weighed. The sum of the weights of the perirenal adipose tissue and the periovary adipose tissue was evaluated as visceral fat. As a test group,
A group added with 1.7% by weight of pomegranate seed oil (1% by weight as punicic acid) and 5.3% by weight of soybean oil (pomegranate seed oil group) prepared in the same manner as in Example 1, and soybean as a control group 7% by weight of a DHA-rich fish oil (containing 20% DHA, manufactured by Harima Chemicals Co., Ltd.), which is known to have an obesity-reducing effect, as a group to which 7% by weight of oil was added (soybean oil group) and a comparative group
(Fish oil group) was added.

As a result, the food consumption between each group during the test period,
No significant change was observed in weight gain. Table 7 shows the results of the measurement of the weight of each organ as the ratio of the weight of the organ to the weight of the organ. In the fish oil group, a significant visceral fat accumulation inhibitory effect was observed. In the pomegranate seed oil group, a visceral fat accumulation inhibitory effect equivalent to that of fish oil was observed.

[0061]

[Table 7]

Example 6 Using Highly Conjugated Unsaturated Fatty Acids
That 10% cancer cell proliferation inhibitory effect bovine fetal serum added RPMI-1640 medium (Gibco
200 μl of human colorectal cancer-derived cells DLD-1 cells (5 × 10 ⁵ cells / ml) suspended in BRL) were dispensed into each well of a 96-well plate, and were incubated at 37 ° C. under 5% CO ₂ . After culturing for 24 hours, the hexane solution of the pomegranate seed oil-derived fatty acid or the tung oil-derived fatty acid prepared in Example 1 was sufficiently volatilized under a nitrogen stream, and then dissolved in dimethyl sulfoxide. Then, a fatty acid solution prepared in advance by dilution with phosphate buffered saline (PBS) was added, and the cells were further cultured for 20 hours.
Thereafter, [3H] thymidine (manufactured by Amersham Japan) was added at 1 μci / 10 μl / well, and the cells were further cultured for 4 hours. After washing the cells with PBS, 2N-NaO
After dissolving with 100 µl of H solution and neutralizing with 50 µl of 4N-HCL, radioactivity was measured using a liquid scintillation counter. A test using PBS instead of the test sample was used as a control. Table 8 shows the results. Tung oil and pomegranate seed oil showed an inhibitory effect on cancer cell growth.

[0063]

[Table 8]

Example 7 Safety Evaluation of Pomegranate Seed Oil Pomegranate seed oil was administered by gavage at a rate of 10 g / kg to five 6-week-old female ICR CD-1 mice (manufactured by Charles River Co., Ltd.). The general condition of the mice was observed for one week. As a result, no particular toxicity symptoms were observed. Also,
A group of 8 mice / group were prepared in a standard mixed feed for fat-removed mice and rats (AIN-93G for growing season, manufactured by Oriental Yeast Co., Ltd.) and 2% by weight of soybean oil in the same manner as in Example 1. Feed with 7% by weight of seed oil (pomegranate seed oil group), feed with 8.5% by weight of soybean oil and 0.5% by weight of fatty acid derived from pomegranate seed oil prepared in the same manner as in Example 1 ( Pomegranate seed oil-derived fatty acid group), and feed (soybean seed oil group) to which 9% by weight of soybean oil was added,
They were bred for 4 weeks, and were subjected to weight change, food consumption change, general condition, and main tissue weight measurement and macroscopic observation after 4 weeks.
As a result, no difference in body weight change and food consumption was observed between the groups, and no particular toxicity findings were observed.

(Example 8) Margari containing pomegranate seed oil
Production of hardened soybean oil (mp40 ° C) 60% by weight, palm oil 20
80% by weight of a fat and oil composition comprising 20% by weight of corn oil
Parts by weight, 0.3 parts by weight of lecithin, 0.1 part of monoglyceride.
3 parts by weight, 16 parts by weight of water, 2 parts by weight of salt, 5 parts by weight of pomegranate seed oil prepared in the same manner as in Example 1, a small amount of vitamin E as an antioxidant, and TK at 60 ° C. while blowing nitrogen gas After emulsification at 50 V for 15 minutes using a homomixer, the mixture was rapidly cooled and kneaded at 15 ° C. to obtain a sheet-like margarine having no problem in flavor.

(Example 9) Margari containing pomegranate seed oil
Of pomegranate seed oil-containing margarine 1 obtained in Example 8
250 g, light flour 1500 g, strong flour 1000 g, and powdered milk 60 g were mixed, and an aqueous solution obtained by dissolving 45 g of salt and 1500 g of sugar in 1250 ml of water was added thereto. The mixture was gently mixed to form a dough, which was spread into a sheet, and folded three times. After repeated molding, a baked pie was produced in an oven.

Example 10 Fatty Acid Derived from Pomegranate Seed Oil
Manufacture of bread containing bread ingredients (100 parts by weight of strong flour, 3 parts by weight of yeast, 3 parts by weight of milk powder, 5 parts by weight of sugar, 70 parts by weight of water, salt 2
Parts by weight, margarine 7 parts by weight)
1 part by weight of pomegranate seed oil-derived fatty acid obtained in the same manner as in Example 1 is added to 0 parts by weight, kneaded and fermented to make a dough, and this dough is floored at 25 ° C. for a floor time of 60 minutes. And after dividing, take 30 minutes bench time at room temperature, then put in a pan mold, temperature 38 ℃,
After being kept under the condition of 90% humidity for 60 minutes, it was baked in an oven (at 190 ° C. for 45 minutes) to produce bread.

Example 11 Contains Pomegranate Seed Oil
Production of chocolate 22 parts by weight of cocoa mass, 10 parts by weight of cocoa butter, 10 parts by weight of cocoa butter substitute oil and fat, 8 parts by weight of whole milk powder, 1 part by weight of pomegranate seed oil prepared in the same manner as in Example 1
The mixture was mixed well at ℃, passed through a refiner, conching and tempering, and then cooled by flowing into a mold to produce a plate chocolate.

(Example 12) Pomegranate seed oil is contained
Production of whipped cream 70 parts by weight of rapeseed hardened oil having a rising melting point of 34 ° C. and a rising melting point of 3
In a mixed oil consisting of 30 parts by weight of hardened coconut oil at 2 ° C., 0.8 parts by weight of synthetic diglycerol stearate, 0.6 parts by weight of soybean lecithin, and 3 parts by weight of pomegranate seed oil are added and dissolved at an oil temperature of 70 ° C. as emulsifiers. Thus, an oil / fat composition was obtained.
Separately, 0.1 part by weight of sodium hexametaphosphate was added to 54.9 parts of skim milk and heated to 55 ° C. while stirring. To this skim milk, 45 parts by weight of the emulsifier-added oil / fat composition was added, and preliminarily emulsified while maintaining the temperature at 65 ° C., and the mixture was passed through a homogenizer for the first time, at a pressure of 80 kg / cm ² , and for the second time, at a pressure of 20 kg / cm ² . After homogenization at 95 ° C, 1
A sterilization treatment was performed for 5 seconds, and the mixture was further cooled to 5 ° C. using a plate cooler, and then aged in a 5 ° C. thermostat for 24 hours to obtain a foamable synthetic cream. The obtained cream had no problem in flavor.

(Example 13) Pomegranate seed oil is contained
Production of French dressing Salad oil 150 parts by weight, pomegranate seed oil 30 parts by weight,
100 parts by weight of wine vinegar, a little salt and pepper were added to produce a French dressing having no problem in flavor.

(Example 14) Conjugated unsaturated fatty acid, or
Production of conjugated unsaturated fatty acid triglyceride-containing beverage Pomegranate seed oil, bitter melon seed oil, calendula seed oil, balsam seed oil, pomegranate seed oil-derived fatty acid, tung oil-derived fatty acid, and calendula seed oil-derived fatty acid prepared according to the method of Example 1 Or 1 part by weight of a balsam seed oil-derived fatty acid, 8.5 parts by weight of a mixed emulsifier, and reduced starch saccharified product 9
0.5 part by weight was mixed and emulsified, and immediately sterilized by heating at 80 ° C. for 10 minutes. 5 parts by weight of the resulting emulsion was mixed with 5 parts by weight of granulated sugar, 14 parts by weight of liquid sugar, 1 part by weight of flavor, and 0.1 part of citric acid. 5 parts by weight, 0.2 parts by weight of sodium citrate, 74 parts by weight of water and pH 3.3 were mixed to obtain a beverage.

Example 15 Preparation of Oral Capsule 40 mg of pomegranate seed oil, bitter melon seed oil, calendula seed oil, balsam seed oil or commercial tung oil obtained by the same method as in Example 1, lactose 200 mg, starch 70m
g, polyvinylpyrrolidone 5, crystalline cellulose 35 mg
After mixing, the mixture was filled in a # 3 gelatin capsule, and the surface was gelatin-coated to prepare an oral capsule.

Example 16 Preparation of Oral Tablet 5 g of pomegranate seed oil-derived fatty acid, tung oil-derived fatty acid, calendula seed oil-derived fatty acid or balsam seed oil-derived fatty acid obtained in the same manner as in Example 1, and 70 g of lactose , 30 g of corn starch are uniformly mixed, and 25 ml of a 10% hydroxypropylcellulose solution is added thereto, followed by stirring and granulation. After drying, this was sized, 2 g of magnesium stearate and 2 g of talc were added and mixed, and tablets were produced with a rotary tableting machine.

Example 17 Trigly Conjugated Trienoic Acid
Preparation of Ceride- Containing Emulsifier Intralipi manufactured by Baxter
d) 5 parts by weight of pomegranate seed oil, calendula seed oil, catalpa seed oil, bitter melon seed oil, balsam seed oil, or tung oil obtained in the same manner as in Example 1 were added to 95 parts by weight and emulsified, and conjugated trienoic acid triglyceride was added. A contained emulsifier was obtained.

Example 18 Conjugated unsaturated fatty acids or
Preparation of pet food containing triglyceride containing unsaturated fatty acid 80 parts by weight of chicken, 10 parts by weight of ground beef lean, 10 parts by weight of soybean protein, prepared in the same manner as in Example 1,
Pomegranate seed oil, bitter melon seed oil, calendula seed oil, balsam seed oil, pomegranate seed oil-derived fatty acid, tung oil-derived fatty acid, calendula seed oil-derived fatty acid, or balsam seed oil-derived fatty acid prepared by the same method as in Example 1 Parts by weight, 1 part by weight of chemical seasoning, 1 part by weight of tocopherol,
In addition, knead a little calcium, a little vitamins, a little starch, a little sorbitol with a food cutter, fill the sheep intestine, cook at 90-95 ° C, then 50 ° C
To dry dry sausage type pet food.

[0076]

The oil / fat composition containing a conjugated trienoic acid or a conjugated tetraenoic acid, a salt thereof, or an ester derivative thereof exhibiting a PPAR agonist activity has a visceral fat reducing effect, a visceral fat accumulation suppressing effect, and a lipid metabolism disorder. It is used as a composition for health drinks, health foods, supplementary foods, and pharmaceuticals for the purpose of improving human diet and the above-mentioned physical tendencies because it has an improvement effect, an effect of improving glucose metabolism abnormality, and an effect of suppressing cancer cell growth. can do. Further, it can be used as a feed for preventing and treating pet obesity and diabetes, or as a feed for preventing and treating cancer.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A23L 1/24 A23L 1/30 B 1/30 A61K 35/78 C 2/52 L A61K 35/78 ST A61P 3/06 35/00 A61P 3/06 C11B 1/10 35/00 C11C 1/04 C11B 1/10 3/00 C11C 1/04 3/04 3/00 A23D 9/00 516 3/04 A23L 2 / 00F (72) Inventor Shoichi Kato 157-100 Nishifutami, Futami-cho, Akashi-shi, Hyogo Prefecture (72) Inventor Takehiko Oto 2-17 Kasumigaoka, Tarumizu-ku, Kobe-shi, Hyogo Prefecture

Claims (16)

[Claims] 1. A conjugated triene structure (—CH ＝ CH—CH ＝ CH—CH ＝ CH—) or a conjugated tetraene structure (—CH ＝ CH—CH ＝ CH—CH) as an active ingredient.
= CH-CH = CH-). A peroxisome activator-responsive receptor agonist comprising at least one selected from the group consisting of conjugated unsaturated fatty acids having 10 to 26 carbon atoms and salts and ester derivatives thereof. 2. A conjugated triene structure (—CH ＝ CH—CH ＝ CH—CH ＝ CH—) in the molecule as the active ingredient.
The peroxisome activator-responsive receptor agonist according to claim 1, comprising at least one selected from conjugated unsaturated fatty acids having 10 to 26 carbon atoms, salts thereof, and ester derivatives thereof. 3. As the active ingredient, at least one conjugated unsaturated fatty acid selected from punicic acid, calendic acid, α-eleostearic acid, β-eleostearic acid, catalpic acid and parinaric acid, The peroxisome activator-responsive receptor agonist according to claim 1, which comprises a salt thereof or an ester derivative thereof. 4. The peroxisome activator-responsive receptor agonist according to claim 3, wherein the active ingredient contains at least one of ethyl ester and glycerol ester derivatives of the conjugated unsaturated fatty acid. 5. The peroxisome activator-responsive receptor agonist according to claim 1, wherein the peroxisome activator-responsive receptor is a peroxisome activator-responsive receptor γ. 6. An oil / fat composition comprising the peroxisome activator-responsive receptor agonist according to claim 1. 7. An extract or a processed product thereof of at least one plant seed selected from plants belonging to the pomegranate family, the asteraceae family, the daceaceae family, the dwarf family, the botanical family, and the bollaceae family. 7. The fat or oil composition according to claim 6, wherein 8. The oil or fat according to claim 7, wherein the plant seed extract is at least one selected from pomegranate seed oil, calendula seed oil, tung oil, bitter gourd seed oil, catalpa seed oil, and balsam seed oil. Composition. 9. A pharmaceutical comprising the peroxisome activator-responsive receptor agonist according to claim 1 as an active ingredient. 10. An agent for reducing visceral fat and inhibiting visceral fat accumulation, comprising the peroxisome activator-responsive receptor agonist according to any one of claims 1 to 5 as an active ingredient. 11. An agent for preventing and improving abnormalities in lipid metabolism, comprising the peroxisome activator-responsive receptor agonist according to any one of claims 1 to 5 as an active ingredient. 12. A preventive and ameliorating agent for abnormal glucose metabolism, comprising the peroxisome activator-responsive receptor agonist composition according to any one of claims 1 to 5 as an active ingredient. 13. A prophylactic and therapeutic agent for cancer comprising the peroxisome activator-responsive receptor agonist according to any one of claims 1 to 5 as an active ingredient. 14. A food or drink comprising the peroxisome activator-responsive receptor agonist according to claim 1. 15. The food or drink according to claim 14, which is at least one selected from margarine, shortening, edible oil, dressing, mayonnaise, chocolate, cookies, pie, and bread. 16. A feed containing the peroxisome activator-responsive receptor agonist according to any one of claims 1 to 5.