JP2007099777A - Lipid metabolism improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a food, a medicine or a feed having lipid metabolism improving actions or anti-obestic actions. <P>SOLUTION: The food, medicine or feed comprises evodiamines as an active ingredient. The food, medicine or feed has the lipid metabolism improving actions or anti-obestic actions. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a food, medicine or feed having an action of improving lipid metabolism or an anti-obesity action.

Lipid metabolism refers to the process of catabolizing (degrading) and assimilating (accumulating) fats mainly composed of food-derived triglycerides. In a broad sense, lipid energization, fatty acid biosynthesis, and acylglycerol biosynthesis Phospholipid metabolism, cholesterol metabolism, and the like.
Obesity refers to a state where more than appropriate fat has accumulated in adipose tissue in various parts of the body, and is known to have a deep relationship with hypertension, hyperlipidemia, diabetes, stroke, arteriosclerosis, myocardial infarction, and the like.

  Anti-obesity, that is, methods for treating or preventing obesity, are roughly classified into two types: a method for suppressing energy intake and a method for promoting energy consumption. Examples of the former method include ingestion or administration of sugar or fat substitutes, dietary fibers such as konjac, or absorption inhibitors or appetite suppressants such as Gymnema Sylvestre (see Patent Document 1). Examples of the latter method include exercising or taking or taking a lipid metabolism improving agent such as capsaicin (see Patent Document 2) or soybean peptide (see Non-Patent Document 1). However, it is difficult to continue exercising, and capsaicin has problems such as limited intake due to spiciness. For this reason, development of an effective lipid metabolism improving agent is desired.

For livestock, poultry or farmed fish, concentrated feed is currently administered in an attempt to promote growth, but as a result, abnormal lipid metabolism may occur in these livestock, poultry or farmed fish. In pets, obesity due to overfeeding of feed and lack of exercise may be a problem.
Evodiamine is a compound obtained from Gumyu of the citrus family that is a kind of herbal medicine (see Non-Patent Document 2).

  As the pharmacological action of evodiamine, in addition to diuretic action and sweating action, a chilling ameliorating agent (see Patent Document 3), a brain function improving agent (see Patent Document 4), an anti-inflammatory external preparation (see Patent Document 5), a cardiotonic agent ( Although known as an action of relaxing blood vessels (see Non-Patent Document 3), analgesic action (see Non-Patent Document 4), etc., it is known with respect to lipid metabolism improvement or anti-obesity. Absent.

  Rutacarpine, dehydroevodiamine, and hydroxyevodiamine are all structurally similar compounds obtained from Goshuyu as well as evodiamine. In addition, the former two compounds have physiological activity as well as evodiamine (see Non-Patent Documents 5 and 6). Furthermore, rutaecarpine has an analgesic action similar to evodiamine (see Non-Patent Document 7). However, none of the above three compounds is known for improving lipid metabolism or anti-obesity.

Tetradium ruticarpum genus is a plant belonging to the (Evodia) tetradium ruticarpum (Evodia rutaecarpa) is generally stomachic, diuretic, besides being used as analgesics, hair growth nourishing food (see Patent Document 7), tetradium ruticarpum extract containing cosmetics (Patent The action as an alcohol absorption inhibitor (see Patent Document 9), a therapeutic agent for periodontal disease (see Patent Document 10), and the like are known. However, nothing is known about the effects of lipid metabolism improvement or anti-obesity.

Hazarea ( F. rhetza ), a plant belonging to the genus Fagara , is a traditional medicinal plant in Indonesia and is known to be effective in malaria, diarrhea, and vomiting (see Non-Patent Document 8). However, nothing is known about the effects of lipid metabolism improvement or anti-obesity.
Zanthoxylum a plant belonging to the (Zantoxylum) Zantokishiramu Retsua (Z. Rhetsa), Zantokishiramu Badoranga (Z. Budrunga) has been reported to be cytotoxic (see Non-Patent Document 9). However, nothing is known about the effects of lipid metabolism improvement or anti-obesity.

Arari Opsys a plant belonging to the genus (Araliopsis) Arari Opsys Tabouenshisu (see Non-Patent Document 10) (A. tabouensis), Arari Opsys Soyauki (A. soyauxii) is known to be effective in gonorrhea. However, nothing is known about the effects of lipid metabolism improvement or anti-obesity.
JP-A-6-343421 Japanese Examined Patent Publication No. 4-58303 JP-A-4-305527 JP 63-287724 A Japanese Unexamined Patent Publication No. 6-312932 JP-A-60-224622 JP 61-1619 JP 59-122414 A JP-A-3-264534 JP-A-62-148426 Journal of Soy Protein Nutrition Society, 13, 53-58 (1992) Journal of Pharmaceutical Sciences, 75, 612-613 (1986) European Journal of Pharmacology, 215, 277-283 (1992) Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.), 20 (3), 243-248 (1997) European Journal of Pharmacology, 257, 59-66 (1994) Journal of Cardiovascular Pharmacology (J. Cardiovasc. Pharmacol.), 27 (6), 845-853 (1996) Biological and Pharmaceutical Bulletin, 20 (3), 243-248 (1997) Chemical and Pharmaceutical Bulletin (Chem. Pharm. Bull.), 40 (9), 2325-2330 (1992) Journal of Natural Products (J. Nat. Prod.), 42 (6), 697 (1979) Planta medica, 29, 310-317 (1976)

  An object of the present invention is to provide foods, pharmaceuticals or feeds having lipid metabolism improving action or anti-obesity action.

  The present invention is a compound of formula (I)

[Where:

は

Is

（式中、Ｒ^１は水素またはヒドロキシを表し、Ｒ^２は水素または低級アルキルを表すか、Ｒ^１とＲ^２が一緒になって結合を表す)、または

(Wherein R ¹ represents hydrogen or hydroxy, R ² represents hydrogen or lower alkyl, or R ¹ and R ² together represent a bond), or

（式中、Ｒ^３は低級アルキルを表す）を表し、ｎは

(Wherein R ³ represents lower alkyl) and n represents

が

But

のとき０を表し、

Represents 0,

が

But

のとき１を表し、Ｘ⁻は陰イオンを表す］で表される化合物またはその塩（以下、エボジアミン類と総称する）を有効成分として含有してなり、脂質代謝改善作用または抗肥満作用を有する食品に関する。

And X ⁻ represents an anion] or a salt thereof (hereinafter collectively referred to as evodiamine) as an active ingredient, and has a lipid metabolism improving action or an anti-obesity action. Regarding food.

  The present invention also relates to a lipid metabolism improving agent or anti-obesity agent comprising evodiamine as an active ingredient, a lipid metabolism improving method or anti-obesity method comprising administering an effective amount of evodiamines, lipid metabolism improving or anti-obesity agent. Use of evodiamines for the manufacture of pharmacological compositions useful for obesity, use of evodiamines for improving lipid metabolism or anti-obesity, or pharmacologically acceptable dosage forms with pharmacologically acceptable carriers And a composition for improving lipid metabolism or anti-obesity comprising an effective amount of evodiamines.

The present invention also relates to a feed comprising evodiamine as an active ingredient and having a lipid metabolism improving action or an anti-obesity action.
The present invention also includes a feed additive having evodiamines as an active ingredient and having lipid metabolism-improving action or anti-obesity action, a method for improving lipid metabolism in animals, or administration of an effective amount of evodiamines. With obesity methods, the use of evodiamines for the preparation of feed additives useful for improving lipid metabolism or anti-obesity, the use of evodiamines for improving animal lipid metabolism or anti-obesity, or with pharmacologically acceptable carriers The present invention relates to a composition for improving lipid metabolism or anti-obesity in animals comprising an effective amount of evodiamines in a pharmacologically acceptable dosage form.

  ADVANTAGE OF THE INVENTION According to this invention, the foodstuff, pharmaceutical, or feed which has a lipid metabolism improvement effect or an anti-obesity effect can be provided.

In the definition of each group of formula (I), the lower alkyl of R ² or R ³ is the same or different and is linear or branched having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, Butyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl and the like, preferably methyl.

  Examples of the anion include a hydrogen ion, a halogen ion, an anion derived from an inorganic acid, an anion derived from an organic acid, and the like. Examples of the halogen ion include fluorine ion, chlorine ion, bromine ion and iodine ion. Examples of the anion derived from an inorganic acid include nitrate ion, sulfate ion, phosphate ion, carbonate ion and the like. Examples of the anion derived from an organic acid include anions derived from carboxylic acids such as formate ion, acetate ion, lactate ion, citrate ion, phosphate ion and glutamic acid.

Examples of the salt include acid addition salts such as organic acid salts such as hydrochloride, maleate, tartrate and citrate.
Specific evodiamines represented by the formula (I) include evodiamine, rutacarpine, dehydroevodiamine, hydroxyevodiamine and the like.
Evodiamine has the formula (II)

It is a compound shown by these.
As evodiamine, commercially available products (manufactured by Kishida Chemical Co., Ltd.) may be used. For example, JP-A 52-77098, JP-B 58-434 [[(R, S) -Evodiamine] or Journal of the Chemical・ Society Chemical Communications (J. Chem. Soc. Chem. Commun.), 10 , 1092-1093 (1982) [(S) -evodiamine] or by the genus Goshuyu of the citrus family ( Evodia rutaecarpa ), Hongoshuyu ( E. officinalis ), E. danielli , E. meliaefolia, etc.], Ginseng ( Fagararhetza, etc.), Salamanders ( Zantoxylum rhetsa ), Zantokishiramu Badoranga (Z.budrunga), Zantokishiramu flavum (Z. flavum), etc.], Arari Opsys genus [Arari Opsys Tabouenshisu (Araliopsis tabouensis) From Arari Opsys Soyauki (A.soyauxii), etc.] plants of plants containing the evodiamine such as, for example, Journal of Pharmaceutical Sciences (Journal of Pharmaceutical Sciences), 75 , according to 612-613 (1986) It may be prepared by a method and used.

Evodiamine has optical isomers. According to the chemical synthesis method, both S-isomer and R-isomer are obtained, and S-isomer is obtained from plants. In the present invention, any isomer of S-form, R-form and mixtures thereof may be used, but S-form is preferably used.
Lutaecarpine has the formula (III)

It is a compound shown by these.
A commercially available product (made by Kishida Chemical Co., Ltd.) may be used as rutaecarpine, for example, JP-A 53-77100, Journal of Organic Chemistry (J. Org. Chem.), 50 , 1246-1255 (1985). ), Or the genus Goshuyu (goshuyu, jujube, etc.), the dog genus (hazalea, etc.), the salamander ( Zantoxiram leza, Zantoxilam limonella ( Z.limonella ), Zantoxilam integrafolioram ( Z. integrifoliolum ) etc.] from a plant body containing a rutaecarpine, for example, Chemical and Pharmaceutical Bulletin (Chem. Pharm. Bull.), 37 , 1820-1822 (1989)] And may be used.

  Dehydroevodiamine has the formula (IV)

It is a compound shown by these.
In formula, X < ^- > represents an anion and an anion is synonymous with the above.
Dehydroevodiamine can be obtained, for example, by a chemical synthesis method described in Journal of Organic Chemistry (J. Org. Chem.), 50 , 1246-1255 (1985), or in the genus Goshuyu (Goshuyu, Juyoushi). From a plant containing a dehydroevodiamine such as, for example, the method described in American Journal of Chinese Medicine, 10 , 75-85 (1982). It may be used.

  Hydroxyevodiamine has the formula (V)

It is a compound shown by these.
Hydroxyevodiamine is, for example, from a plant of a plant containing hydroxyevodiamine such as genus Goshuyu (goshuyu, etc.), salamander (Zantoxiram lezza, etc.), arariopsis (arariopsis tabouensis, etc.) It may be prepared by the method described in Journal, 82 , 619-626 (1962).

In the present invention, purified products or pure products may be used as evodiamines, but unrefined or crude evodiamines may be used as long as they do not contain impurities that are inappropriate as foods, pharmaceuticals, and feeds.
Unpurified or crude evodiamines include, for example, plants containing evodiamines, preferably plants belonging to the citrus family, more preferably Evodia , Fagara , Zanthoxylum or Arari. Examples of plants belonging to the genus Araliopsis , such as leaves, stems, bark, roots, fruits, etc., or pulverized products, extracts, crude products, or purified products containing evodiamines obtained from the plants. .

As the plant body containing evodiamines, fruits, bark or root bark such as goshuyu, hazalea, xanthoxilam leza, arariopsis tabouensis or jujube are preferably used.
The pulverized product containing evodiamines can be obtained by drying and then pulverizing a plant body containing evodiamines.

  In the extract containing evodiamines, the pulverized product can be used alone or in combination with water, alcohols such as methanol, ethanol, propanol and butanol, hydrophilic solvents such as acetone, or organic solvents such as diethyl ether, ethyl acetate, chloroform and benzene. It can be obtained by using in combination and extracting.

  The crude product or purified product of evodiamines can be obtained by converting the pulverized product or the extract into a porous polymer such as Diaion HP-20 (registered trademark; manufactured by Mitsubishi Chemical Corporation), Sephadex LH-20 (registered trademark; Pharmacia LKB Bio). Technology Sepadex, normal phase silica gel, reverse phase silica gel, polyamide, activated carbon or cellulose, etc., and column chromatography or preparative high performance liquid chromatography, and thin layer chromatography (developing solvent) : 95% methanol, color former: 5% ethanol sulfate), and evodiamines can be purified by fractional purification while confirming the target component. In order to obtain a purified or pure product of evodiamines, it is desirable to combine and repeat the above operations as appropriate, and perform a recrystallization operation or the like as necessary.

  The food of the present invention contains evodiamine so as to contain 0.001% or more, preferably 0.01 to 20%, more preferably 0.05% to 1% of evodiamine in food ingredients, in particular, food ingredients that essentially do not contain evodiamine. Can be processed and produced by using a general food production method by adding the product in the form of a pure product, a purified product, a crude product or the like, or a lipid metabolism improving agent or an anti-obesity agent.

  Food types include juices, soft drinks, teas, lactic acid bacteria beverages, fermented milk, frozen desserts, dairy products (butter, cheese, yogurt, processed milk, skim milk, etc.), livestock meat products (ham, sausage, hamburger, etc.) ), Fish-paste products (bowl, bamboo rings, fried fish cakes, etc.), egg products (boiled rolls, egg tofu, etc.), confectionery (cookies, jellies, snacks), breads, noodles, pickles, salmon products, dried fish, boiled and salted Products, soups, seasonings and the like.

  As the form of the food of the present invention, if it contains evodiamine, in addition to forms such as frozen food, powdered food, sheet food, bottled food, canned food, retort food, capsule food, tablet food, etc. It may be in any form, such as natural liquid foods containing protein, saccharides, fats, trace elements, vitamins, emulsifiers, fragrances, processed forms such as semi-digested and component nutrients, and drinks.

  The food of the present invention is used for the treatment, prevention or improvement of diseases such as fatty liver, hypertension, hyperlipidemia, arteriosclerosis, diabetes, myocardial infarction as well as diet food as health food and functional food. May be. In this case, it is preferable that the processed food is 0.1 to 2000 mg orally taken as evodiamine per day.

  The lipid metabolism improving agent or anti-obesity agent of the present invention may be in any dosage form such as tablets, powders, fine granules, granules, capsules, syrups, intestinal solvents, troches, injections, infusions and the like. The dosage form of the preparation is not particularly limited, and examples of the administration route include oral administration, intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, and the like. Of these, oral administration is preferred. In the case of oral administration, pure products, purified products, crude products, etc. of evodiamines may be administered as they are, but together with pharmaceutically acceptable excipients, tablets, powders, fine granules, granules, capsules It may be administered in the form of an agent, syrup and the like. As excipients, sugars such as sorbitol, lactose, glucose, lactose, dextrin, starch, crystalline cellulose, inorganic substances such as calcium carbonate and calcium sulfate, distilled water, sesame oil, corn oil, olive oil, cottonseed oil, etc. are generally used. Any of them can be used. In formulating, additives such as binders, lubricants, dispersants, suspending agents, emulsifiers, diluents, buffers, antioxidants, and bacterial inhibitors can be used. As an injection, an appropriate buffer, an isotonic agent and the like can be added and dissolved in oil such as vegetable oil.

The dosage varies depending on age, sex, degree of disease, dosage form, number of doses, dosage form, etc., but in the case of oral administration for adults, evodiamines as active ingredients are 0.1 to 2000 mg / day 1 It is appropriate to administer in 4 divided doses. Moreover, the dosage outside the said restriction | limiting can also be used as needed.
The lipid metabolism improving agent or anti-obesity agent of the present invention can be used for treatment and prevention of diseases such as fatty liver, hypertension, hyperlipidemia, arteriosclerosis, diabetes, myocardial infarction and obesity.

The feed of the present invention may be any feed that has a lipid metabolism improving action or an anti-obesity action on animals such as mammals, birds, reptiles, amphibians, fish and the like, for example, for pets such as dogs, cats, rats, etc. Examples thereof include feed, livestock feed such as cattle and pigs, poultry feed such as chicken and turkey, and cultured fish feed such as Thailand and yellowtail.
The feed additive of the present invention may use evodiamines in the form of pure products, purified products, roughly purified products, etc., or evodiamines obtained from plants containing evodiamines as they are or from the plants. It may be used as a pulverized product, extract, crude purified product or purified product. The feed additive may be mixed or dissolved in accordance with a conventional method, if necessary, and processed into a powder, granule, pellet, tablet, or various liquid forms, and used.

The feed of the present invention is obtained by blending the feed additive into the feed. The blending amount of the feed additive of the present invention in the feed is appropriately selected according to the type of feed, the effect expected from the intake of the feed, and the like. In general, the feed of the present invention is such that the feed raw material, particularly the feed raw material that does not substantially contain evodiamines, contains 0.001% or more, preferably 0.01 to 20%, more preferably 0.05% to 1% of evodiamine. The feed of the present invention can be processed and produced by adding an additive and using a general feed production method.
Test Example 1 Effect on Visceral Fat of Mice The following experiment was conducted using a feed containing evodiamine.

 C3H male mice 9 weeks old were preliminarily raised for 8 days in the feed A prepared with the composition shown in Table 1 and without addition of evodiamine. After completion of the preliminary breeding, the animals were divided into two groups of 4 each, and feed A was prepared for the mice in one group (feed A intake group) and the composition in Table 1 was prepared in the other group (feed B intake group). Feed B supplemented with evodiamine was fed for 12 days each, fasted for 1 day, and then sacrificed on day 13. Immediately after sacrifice, fat around the kidney and testicles was extracted and weighed. The feed intake during the test period was measured every day.

結果を第２表に示す。

The results are shown in Table 2.

脂肪量について、飼料Ｂの摂取群は、飼料Ａの摂取群に比べ、腎周囲において有意に減少した。また、睾丸周囲脂肪量も飼料Ｂの摂取群で減少傾向を示した。飼料摂取量は両群間に有意な差はなく、嗜好上の問題はなかった。このように、エボジアミンは脂質代謝改善作用または抗肥満作用を有するものであった。
試験例２ ラットの体重、内臓脂肪、脂肪分解に対する効果
参考例１で調製したゴシュユ抽出物を含有する飼料を用い、以下の実験を行った。

Regarding the amount of fat, the diet B intake group significantly decreased around the kidney as compared to the diet A intake group. Moreover, the testicular fat amount also showed a decreasing tendency in the feed B intake group. There was no significant difference in feed intake between the two groups, and there was no preference problem. Thus, evodiamine has a lipid metabolism improving action or an anti-obesity action.
Test Example 2 Effects on rat body weight, visceral fat, and lipolysis The following experiment was conducted using the feed containing the Goshuyu extract prepared in Reference Example 1.

  SD male rats 4 weeks old were preliminarily raised for 7 days in a low-fat diet C prepared with the composition shown in Table 3 to which no Goshuyu extract was added. After completion of the preliminary breeding, 3 animals with no significant difference in body weight were divided into 9 groups. One animal in each group was fed with feed E, which is a high-fat feed supplemented with goshuyu extract after fasting for one day. The remaining two of each group have the same amount of feed C, which is a low-fat feed to which no Goshuyu extract is added, and feed D, which is a high-fat feed, in the same amount as one in the same group of feed E group. Give, pair feeding. Since the fat content is different between the feed C and the feed E, when the same amount is consumed, the calorie intake by the feed C is about 78% of the intake calorie of the feed E. The above breeding was carried out for 21 days and fasted for one day, and then sacrificed. Immediately after sacrifice, fat around the kidney and testicles was extracted and weighed. The lipolytic activity was also measured by the following method. During the test period, the body weight was measured every day.

Measurement of lipolytic activity:
Shred the perirenal fat of each rat 50 times with scissors, weigh 100-300 mg, add 1.9 ml of 2% albumin-containing Krebs-Ringer bicarbonate buffer (hereinafter abbreviated as KRB buffer) Two samples were prepared, and these samples were reacted at 37 ° C. for 5 minutes. To each sample, 0.1 ml of 0.2 mg / ml noradrenaline-2% albumin-containing KRB buffer was added and reacted at 37 ° C. for 1 hour, which was used as a reaction zone. To another sample, 0.1 ml of 2% albumin-containing KRB buffer was added and ice-cooled for 5 minutes, which was used as a control group before the reaction. Each section was filtered with a 0.45 μm membrane filter (Millipore), the amount of free fatty acid in the filtrate was measured with a commercially available measurement kit (Determiner NEFA Kyowa Medix), and the amount of decomposed triglyceride was calculated. The activity value was obtained by subtracting the value of the control group before the reaction from the value of the reaction group.

結果を第４表に示す。

The results are shown in Table 4.

体重について、飼料Ｅの摂取群は、ほぼ同カロリーの飼料Ｄの摂取群に比べ、有意に増加が抑制された。また、カロリー摂取量当たりの体重増加量は飼料Ｄの摂取群ばかりでなく、総摂取カロリーの少ない飼料Ｃの摂取群に比べても有意に少なかった。

Regarding the body weight, the increase in the feed E intake group was significantly suppressed as compared with the intake group of the feed D having almost the same calories. Further, the amount of weight gain per caloric intake was significantly less than that of the diet D intake group as well as the diet C intake group with a low total intake calorie.

Regarding the amount of fat, the diet E intake group significantly decreased in the perirenal and testicular fat amounts compared to the diet D intake group. Furthermore, the amount of fat around the testicles was significantly reduced as compared to the intake group of diet C, which had a low total calorie intake, and also showed a tendency to decrease around the kidneys.
The lipolytic activity was significantly increased in the diet E intake group compared to the diet C and D intake groups, and lipid metabolism was improved. Thus, the evodiamine-containing goshuyu extract has a lipid metabolism improving action or an anti-obesity action.

Cookies (30 pieces) are produced by the following composition.
Soft flour 100g
74g starch
14g water
Evodiamine 0.6g
2 tsp baking powder
1/2 teaspoon salt
1 egg butter 80g
2 tablespoons of milk
Small amount of honey

Soft drinks (for 10 bottles) are manufactured with the following composition.
Evodiamine 1g
Vitamin C 1g
Vitamin B1 5mg
Vitamin B2 10mg
Vitamin B6 25mg
Liquid sugar 150g
Citric acid 3g
Fragrance 1g
Bring to 1000ml with water.

The bread is made with the following composition.
Evodiamine 2.4g
Powerful powder 1kg
50g sugar
20g salt
Nonfat dry milk 20g
Shortening 60g
Yeast (raw) 30g
East food 1g
650g of water

Tablets (300 mg per tablet) are produced by the conventional method with the following formulation.
Evodiamine 10mg
Lactose 230mg
Corn starch 30mg
Synthetic aluminum silicate 12mg
Carboxymethylcellulose calcium 15mg
Magnesium stearate 3mg

Produce powder (1000mg per packet) in the usual manner with the following formula.
Evodiamine 10mg
Lactose 800mg
Cornstarch 190mg

Hard capsules (360mg per capsule) are manufactured with the following formulation.
Evodiamine 10mg
Lactose 230mg
Cornstarch 100mg
Hydroxypropylcellulose 20mg
Add 10 mg of evodiamine to 230 mg of lactose and 100 mg of corn starch, mix, add 20 mg of an aqueous solution of hydroxypropylcellulose, and knead. Next, granules are produced by an ordinary method using an extrusion granulator. A hard capsule is produced by filling the granule into a gelatin hard capsule.

Produce soft capsules (170mg per capsule) with the following formula:
Evodiamine 10mg
Soybean oil 160mg
Add 10 mg of evodiamine to 160 mg of soybean oil and mix. Next, soft capsules are produced by filling the soft capsules using a rotary soybean automatic molding machine according to a conventional method.

A mouse (mouse) feed (one month) is produced according to the following formulation.
Evodiamine 0.03 g
Casein 20 g
Lard 10 g
Sucrose 10 g
4 g of minerals
Vitamin 1 g
Cellulose powder 2 g
Sodium cholate 0.125 g
Choline chloride 0.2 g
Corn starch 52.645 g

Produce powder (1000mg per packet) in the usual manner with the following formula.
Lutaecarpine 10mg
Lactose 800mg
Cornstarch 190mg

Produce soft capsules (170mg per capsule) with the following formula:
Dehydroevodiamine 10mg
Soybean oil 160mg
Add 10 mg of dehydroevodiamine to 160 mg of soybean oil and mix. Next, soft capsules are produced by filling the soft capsules using a rotary soybean automatic molding machine according to a conventional method.

A mouse (mouse) feed (one month) is produced according to the following formulation.
Hydroxyevodiamine 0.03g
Casein 20g
Lard 10g
Sucrose 10g
4g mineral
Vitamin 1g
Cellulose powder 2g
Sodium cholate 0.125g
Choline chloride 0.2g
Cornstarch 52.645g

A 1000 ml tea drink is produced with the following composition.
Goshuyu Extract (Reference Example 1) 5g
15g tea leaves
Elute with 1000 ml of hot water.

Tablets (300 mg per tablet) are produced by the conventional method with the following formulation.
Goshuyu extract (Reference Example 1) 50mg
Lactose 190mg
Corn starch 30mg
Synthetic aluminum silicate 12mg
Carboxymethylcellulose calcium 15mg
Magnesium stearate 3mg

A chewing gum (30 pieces) is produced by the following composition.
Goshuyu extract (Reference Example 1) 1g
Gum base 25g
63g sugar
10g chickenpox
Fragrance 1g

The candy (for 20 pieces) is manufactured by the following composition.
Goshuyu extract (Reference Example 1) 1g
80g sugar
Minamata 20g
Fragrance 0.1g

Produce soft capsules (170mg per capsule) with the following formula:
Hazarea extract (Reference Example 2) 50mg
Soybean oil 120mg
Add 50 mg of hazarea extract to 120 mg of soybean oil and mix. Next, soft capsules are produced by filling the soft capsules using a rotary soybean automatic molding machine according to a conventional method.

A marmalade is manufactured by the following composition.
Zantoxylam Leza extract (Reference Example 3) 7g
Summer tangerine skin 500g
200g sugar
1 mandarin orange juice

Thai feed is produced with the following composition.
Arariopsis Tabouensis Extract (Reference Example 4) 10g
Fishmeal 25g
Chicken meal 100g
150g meat and bone meal
Fish soluble 25g
260g soybean meal
125g flour
Corn 250g
Wheat germ 40g
Rusanmeal 40g
5g salt
Antioxidant 20g
Reference Example 1 Production Method of Goshuyu Extract 102.5L of ethanol was added to 2.5kg of goshuyu fruits and the mixture was cold-immersed for 2 days. After collecting the extract, the same operation was further repeated twice to obtain a 30 L ethanol extract. This was filtered through a filter cloth (Milactose manufactured by Hoechst), and the filtrate was concentrated to dryness under reduced pressure to obtain 100 g of an extract.
Reference Example 2 Method for Producing Hazarea Extracts 1 L of methanol was added to 200 g of hazarea bark, and the mixture was cooled for 2 days. After collecting the extract, the same operation was further repeated twice to obtain 3 L of ethanol extract. This was filtered through a filter cloth (Milactose manufactured by Hoechst), and the filtrate was concentrated to dryness under reduced pressure to obtain 19.6 g of an extract.
Reference Example 3 Method for Producing Zanthoxylam Leza Extract 1 L of ethanol was added to 200 g of root bark of Zanthoxylam leza, and the mixture was cooled for 2 days. After collecting the extract, the same operation was further repeated twice to obtain 3 L of ethanol extract. This was filtered through a filter cloth (Milactose manufactured by Hoechst), and the filtrate was concentrated to dryness under reduced pressure to obtain 7.1 g of an extract.
Reference Example 4 Method for Producing Arariopsis Tabouensis Extract 1 L of chloroform was added to 250 g of bark of Arariopsis tabouensis, and the mixture was cooled for 2 days. After recovering the extract, the same operation was further repeated twice to obtain 3 L of chloroform extract. This was filtered through a filter cloth (Milactose manufactured by Hoechst), and the filtrate was concentrated to dryness under reduced pressure to obtain 9.6 g of an extract.
Reference Example 5 Determination of Evodiamine Dissolved in ethanol so that the concentration of the extract obtained in Reference Examples 1 to 4 was 0.01% (w / v), and 10 μl of this was analyzed by high performance liquid chromatography (Shimadzu ODS column). : 4.6 mm I.D. 25 cm, mobile phase: 50% acetonitrile aqueous solution, detection wavelength 254 nm).

  The results are shown in Table 5.

Claims (5)

Formula (I)

[Where:

Is

(Wherein R ¹ represents hydrogen or hydroxy, R ² represents hydrogen or lower alkyl, or R ¹ and R ² together represent a bond), or

(Wherein R ³ represents lower alkyl) and n represents

But

Represents 0,

But

And X ⁻ represents an anion] or a salt thereof (hereinafter collectively referred to as evodiamine) as an active ingredient for improving lipid metabolism or anti-obesity tablets, powders, hard capsules Agent or soft capsule.   A drink for improving lipid metabolism or anti-obesity, containing evodiamine as an active ingredient.   The agent according to claim 1 or 2, wherein the evodiamine is an evodiamine selected from evodiamine, rutacarpine, dehydroevodiamine and hydroxyevodiamine.   The agent according to claim 1 or 2, wherein the evodiamine is an evodiamine prepared from a plant belonging to the citrus family. Evodiamine compound is tetradium ruticarpum genus (Evodia), a Inuzanshou genus (Fagara), zanthoxylum (Zanthoxylum) and Arari Opsys genus evodiamine compound which is prepared from a plant belonging to the genus selected from (Araliopsis), according to claim 1 or 2 The agent described.