JP2009234926A - Adrenal gland hypertrophy inhibitor and feedstuff composition or therapeutic composition containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a raw material excellent in an effect of inhibiting the hypertrophy of adrenal gland accompanying the reduction of function of secretory system caused by psychological stress burden, and a feedstuff composition or a therapeutic composition inhibiting the hypertrophy of the adrenal gland caused by the psychological stress burden due to high density breeding, and excellent in safety. <P>SOLUTION: This adrenal gland hypertrophy inhibitor containing naringin and/or narirutin which is a flavone compound contained much in citruses or their processed materials (preferably, the fruit rind or squeezed debris of unshiu mandarin orange) is incorporated into the feedstuff composition of animals, fishes or shellfishes. and the therapeutic composition such as an orally administering agent, a skin preparation for external use, etc. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an adrenal hypertrophy inhibitor containing a flavone compound or a salt thereof selected from the group consisting of nariltin and naringin as an active ingredient, and a feed composition or therapeutic composition containing the same. Specifically, the present invention relates to a material that can effectively suppress adrenal hypertrophy caused by mental stress load, intake of steroids, and the like, and a feed composition or therapeutic composition containing the material.

  In recent years, with the increase in population, securing food has become an important issue, and in response to this, labor concentration and production efficiency have been widely carried out in the agriculture and livestock industries. For example, in raising leg horns and the like, such efficiency as raising a very large number of animals in a cage that can hardly exercise (dense breeding conditions) is performed.

  However, under dense breeding conditions, the stress caused by the breeding conditions may cause a load on the animal, thereby causing adrenal hypertrophy and the like, and the productivity and quality of livestock and poultry are often reduced.

  As a countermeasure, for example, a method for improving the physical fitness by blending antibiotics and the like into the feed has been devised (for example, see Patent Document 1), but problems such as inducing the appearance of drug-resistant pathogens There was a point. In addition, if feed containing chemicals and antibiotics was given, there was concern about adverse effects on the human body.

  Therefore, to suppress adrenal hypertrophy caused by mental stress caused by crowd breeding of animals and seafood such as livestock and poultry, to improve its productivity and quality, and to prevent adverse effects on the human body that consumes it However, it is desired to develop a safe feed that has an excellent ability to suppress adrenal hypertrophy and does not depend on drugs such as chemicals and antibiotics.

  In addition, the problem of adrenal hypertrophy has also become a problem in the human body in recent years. That is, steroids are frequently used as anti-inflammatory agents and anti-menopausal agents, but it has been known that adrenal hypertrophy occurs as a side effect when steroids are ingested. Therefore, development of a therapeutic composition that can suppress adrenal hypertrophy is desired.

  On the other hand, citrus peel such as Satsuma mandarin is called “Chen skin” in Kampo and has been used for prescriptions for healthy stomach, antitussive, expectorant, cold, etc. Active research has been carried out on the effects.

  The present inventor has so far examined the effect of squeezed (juice) squeezed residue of Satsuma mandarin, which contains the same ingredients as Chen, on the stress model. As a result, it has been found that the skin function lowering improvement effect is exhibited by using these externally (Patent Document 2), and the IgA production-constant action is exhibited by oral ingestion (Patent Document 3). Each patent application was filed first.

  However, the effects of the components contained in citrus fruits on the adverse effects of mental stress have not yet been fully studied, and most of Satsuma mandarin peel and squeezed residue are treated as industrial waste. In the present situation, further effective utilization of these is demanded from the viewpoint of the stress improving effect.

  Until now, it has been known that mandarin oranges contain flavone compounds such as naringin and narrutin. Among these, naringin has a blood fatty acid degradation action, an antiallergic action, an immunity enhancement action, an appetite suppression action, etc., and these and aglycone have an action to promote differentiation of preadipocytes into adipocytes. This is gradually being revealed.

  However, it has not been known so far about the excellent inhibitory effect of naringin and / or nariltin on the adverse effects on the secretory system such as adrenal hypertrophy due to mental stress, and no studies from this point of view have been reported. . In addition, there are no known feed compositions blended with feed or therapeutic compositions intended for administration to the human body in order to suppress adrenal hypertrophy that occurs during close breeding of animals or seafood.

JP 2008-001707 A JP 2001-213775 A JP 2005-255574 A

  The present invention has an action of suppressing adrenal hypertrophy due to mental stress caused by crowded breeding and is gentle to the human body and has few side effects, and a feed composition for animals or seafood containing the same or treatment to the human body It is an object to provide a composition for use.

  As a result of intensive studies in view of the above-mentioned problems, the present inventor has found that naringin and / or nariltin, which is a kind of flavone compound contained in citrus fruits such as Unshu mandarin orange or processed products thereof, is secreted by the body due to mental stress. It has been found that it exhibits an excellent inhibitory effect on adrenal hypertrophy due to adverse effects on the system and intake of steroids used as anti-inflammatory agents and anti-menopausal agents, etc., leading to the completion of the present invention. It was.

That is, this invention relates to the adrenal hypertrophy inhibitor shown to the following (1)-(9), and the feed composition or therapeutic composition containing it.
(1) An adrenal hypertrophy inhibitor comprising, as an active ingredient, a flavone compound selected from the group consisting of nariltin and naringin or a salt thereof.
(2) The adrenal hypertrophy inhibitor according to (1), wherein the adrenal hypertrophy occurs under dense breeding conditions.

(3) A feed composition comprising the adrenal hypertrophy inhibitor according to (1) or (2).
(4) The feed composition according to (3), wherein the feed composition is a feed for dense breeding of animals or seafood.
(5) The feed composition according to (3) or (4), wherein the base of the adrenal hypertrophy inhibitor is citrus peel or fruit juice press residue.
(6) The feed composition according to (5), wherein the citrus fruit is selected from the group consisting of mandarin orange, ponkan, hassaku and navel orange.

(7) A therapeutic composition comprising the adrenal hypertrophy inhibitor according to (1) or (2).
(8) The therapeutic composition according to (7), wherein the base of the adrenal hypertrophy inhibitor is citrus peel or fruit juice residue.
(9) The therapeutic composition according to (8), wherein the citrus fruit is selected from the group consisting of mandarin orange, ponkan, hassaku and navel orange.

  The adrenal hypertrophy inhibitor of the present invention exhibits an excellent inhibitory action against adverse effects on the secretory system due to stress load, particularly adrenal hypertrophy caused by mental stress load due to dense breeding. In addition, Naringin and / or Nariltin, which is an active ingredient of the adrenal hypertrophy inhibitor of the present invention, is based on the citrus peel or fruit juice residue, its action is mild and gentle to the human body, and has few side effects, It is also excellent in safety. Furthermore, it effectively uses citrus peels such as Unshu mandarin oranges and squeezed residues, which are often treated as industrial waste, and is excellent in environmental performance and economy.

Hereinafter, embodiments of the present invention will be described.
(1) Naringin and / or Nariltin The adrenal hypertrophy inhibitor of the present invention comprises a flavone compound (flavonoid) selected from the group consisting of naringin and nariltin as an active ingredient. Naringin and / or Nariltin is a characteristic glycoside component that is abundant in citrus fruits and has the following chemical structure.

The naringin and / or nariltin of the present invention may be selected from the aglycones. Moreover, sodium salt is mentioned as a salt of naringin and / or nariltin.
Naringin and / or Nariltin is contained in a large amount in citrus fruits or processed products thereof, and particularly in a citrus fruit skin and a pulp part (sano). For the isolation of naringin and / or nariltin, a conventionally known method can be used.

(2) Citrus or processed product thereof As citrus fruits in the present invention, citrus citrus fruits, ponkan, hassaku, navel orange, valencia orange, kumquat, summer mandarin orange, sweet summer mandarin, Iyokan, grapefruit, lemon, yuzu, sudachi, suruga orange , Decapon, pomelo, bundan and the like. Of these, more preferred are those selected from the group consisting of Satsuma mandarin, Ponkan, Hassaku and Navel orange, and particularly preferred is Satsuma mandarin.

  The structure of citrus fruits is the pericarp on the surface, the white part on the inner wall of the pericarp (medium pericarp), the seeds, the “sano” (fruit pulp) that is normally eaten, and the ginger membrane Wrapping inner bag). Among the citrus components, the flavone compound of the present invention is contained in a large amount, particularly in the pericarp and cypress.

  As citrus fruits or processed products thereof, citrus peel, juice (fruit juice or juice), concentrated concentrate of the juice, dried juice or concentrate thereof, and powdered as necessary Thing (solid), fruit juice compression residue, etc. are mentioned. In addition, examples include citrus peels as they are or dried (freeze-dried products, ventilation-dried products, sun-dried products, etc.) or pulverized products thereof.

  Citrus pressing residue remains after citrus juice is squeezed, and includes fiber, pectin and the like. As the pressing residue used in the present invention, the residue after squeezing may be used as it is, or a powdered product after drying may be used.

  Since the Naringin and / or Nariltin of the present invention is contained in a large amount in the citrus peel and sardine, the citrus fruit or processed product thereof used in the present invention is a citrus peel or fruit juice residue (mainly sausage). Compressed residue) is preferred. Furthermore, since Naringin and / or Nariltin are particularly contained in citrus peel, citrus peel is particularly preferable.

  As the Naringin and / or Narillin which is an active ingredient of the adrenal hypertrophy inhibitor of the present invention, those extracted and isolated from the citrus peel or fruit juice press residue may be used, and Citrus containing a large amount of Naringin and / or Nariltin. The pericarp or fruit juice press residue itself may be used as it is as an adrenal hypertrophy inhibitor of the present invention.

(3) Adrenal hypertrophy inhibitor The adrenal hypertrophy inhibitor of the present invention has an inhibitory action on adrenal hypertrophy. One factor that causes such adrenal hypertrophy is the burden of mental stress. When mental stress is loaded, adrenal hypertrophy occurs as a sign of stress in the secretory system, but the adrenal hypertrophy inhibitor of the present invention has a remarkable inhibitory action on such adrenal hypertrophy. In particular, it has an excellent inhibitory effect on adrenal hypertrophy caused by stress loading due to the dense breeding of animals or seafood.

Another factor that causes adrenal hypertrophy is the intake of steroids. Steroid agents are used as anti-inflammatory agents, anti-menopausal agents, and the like, and in recent years there are many opportunities to take them.
The adrenal hypertrophy inhibitor of the present invention exhibits a particularly remarkable inhibitory effect on adrenal hypertrophy caused by the above factors, but also has an excellent inhibitory effect on adrenal hypertrophy caused by other factors.

(4) Feed composition When the adrenal hypertrophy inhibitor of the present invention is used in a feed for animals or seafood, the target animals or seafood include animals such as poultry and farmed seafood. . More specifically, domestic animals such as pigs, cows, horses, goats, deer, rabbits, goats and sheep; chickens such as broilers and hens; poultry such as ducks, quails, ducks, turkeys, pheasants and geese; monkeys , Mice, rats, guinea pigs, etc .; yellowtail, red sea bream, puffer fish, tuna, flounder, striped mackerel, horse mackerel, salmon, coho salmon, carp, eel, rainbow trout, sweetfish, shrimp (carr shrimp, button shrimp, lobster, lobster, black Aquaculture animals such as tigers), crabs (crab crab, snow crab, blue crab, crab etc.), shellfish (abalone, turban shell etc.).

  The adrenal hypertrophy inhibitor of the present invention can be used in any feed as long as it is conventionally used for animals or fish and shellfish. Such feed is usually corn, bran, rice, wheat, cottonseed meal, milo, soybean meal, fish meal, defatted rice bran, fats and oils, alfalfa, calcium carbonate, calcium phosphate, sodium chloride, choline chloride, various vitamins (vitamins) A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, calcium pantothenate, nicotinic acid amide, folic acid, inorganic salts (magnesium sulfate, iron sulfate, copper sulfate, zinc sulfate, potassium iodide, It is prepared by mixing a part or all of (such as cobalt sulfate).

  Major ingredients in the feed include corn, ground corn, corn flour, corn germ meal, milo, millet, oats, wheat, wheat flour, wheat germ flour, barley, rice, rye, buckwheat and other grains Cereal by-products; rice bran, bran, barley bran and other potatoes, pea seeds, peanut flour, soybeans and other legumes, potato flour and other potatoes; soybean meal, defatted soybeans, cottonseed meal, rapeseed meal , Vegetable oil meal such as sesame meal, sunflower meal, safflower meal, coconut flour, etc .; Manufactured fish; fish meal, meat meal, meat and bone meal, meat meal, meat bone meal, blood meal, feather meal, skim milk powder, dried whey Animal materials such as heavy meal, krill meal, casein and gelatin; yeasts such as brewer's yeast; sugars such as corn starch and dextrin; alfalfa, dried alfalfa powder, grass powder, various leaf meals, soy protein, wheat gluten, Plant proteins such as corn zein; fine powders of inorganic substances such as crystalline cellulose, talc, silica, muscovite, zeolite; inorganic calcium compounds such as calcium carbonate; and inorganic phosphates such as calcium phosphate; Can do. If necessary, the feed may further contain other additives permitted in the livestock field (for example, other antibiotics, fungicides, anthelmintics, antioxidants, etc.).

  The content of the adrenal hypertrophy inhibitor in the feed of the present invention is generally from 0.0001% to 1% by weight, preferably from 0.001% to 3.0% by weight. However, the content of the adrenal hypertrophy inhibitor in the feed composition in the present invention is not limited to the above-mentioned amount, but the type of the target animal, growth stage, age, body weight, environmental conditions, physical condition, feed material The required amount can be appropriately selected and added according to the type, feeding season, etc., and the resulting effect can be adjusted.

(5) Therapeutic composition The therapeutic composition of this invention contains the adrenal hypertrophy inhibitor which uses the specific flavone type compound derived from the citrus fruits or its processed material mentioned above as an active ingredient. The administration route and dosage form of such a therapeutic composition are not particularly limited, and may be, for example, an oral administration agent or a transdermal administration agent. Specifically, liquid or internal preparations such as foods or pharmaceuticals can be mentioned for oral administration, and skin external preparations such as cosmetics and skin external medicines can be mentioned for transdermal administration.

  Examples of internal preparations such as foods and pharmaceuticals include solid preparations such as tablets, powders and granules, liquid preparations, semi-solid preparations and the like, which can be absorbed into the body by oral administration.

  As optional ingredients other than citrus fruits or processed products thereof, if the internal preparation is a food, for example, sweeteners, salting agents, spices, sour seasonings, umami seasonings and other seasonings, emulsifying / dispersing agents, antioxidants, Preservatives, thickeners, binders, fragrances and the like can be exemplified. For pharmaceuticals, excipients, binders, disintegrants, coating agents, lubricants, extenders, diluents, pH adjusters, emulsifying / dispersing agents, stabilizers, miso odorants, coloring An agent etc. can be illustrated.

  Examples of the external preparation for skin include ointments, solutions, patches, sprays, oral preparations, liniments, etc., and the composition can be absorbed into the body by oral (mucosal) administration or transdermal administration. .

  In the case of an ointment, as an optional component other than citrus fruits or processed products thereof, those used in general ointments can be appropriately blended as necessary. For example, fat, fatty oil, lanolin, Vaseline, wax, resin, glycols, higher alcohol, glycerin, emulsifier, suspending agent and the like can be blended. Although the content rate of citrus or its processed material is not specifically limited, For example, about 0.5 to 5 weight% is good.

  In the case of a liquid preparation, as an optional component other than citrus fruits or processed products thereof, those used in general liquid preparations can be appropriately blended as necessary. For example, a preservative (methyl paraoxybenzoate, propyl paraoxybenzoate) ), Sugars, sweeteners, ethanol, fatty oils, soap, glycerin, emulsifiers, suspending agents and the like. Although the content rate of citrus or its processed material is not specifically limited, For example, about 1 to 10 weight% is good.

  In the case of a patch, as an optional ingredient other than citrus fruits or processed products thereof, those used in general patches can be appropriately blended as necessary. For example, kaolin, essential oil ingredients, l-menthol, mint Oil, eucalyptus oil, glycerin, propylene glycol, suspending agent, emulsifier, water and the like can be blended. Although the content rate of citrus or its processed material is not specifically limited, For example, about 0.5 to 5 weight% is good.

  In addition, when used as a cosmetic, for example, hydrocarbons such as squalane, petrolatum, microcrystalline wax, esters such as jojoba oil, carnauba wax, octyldodecyl oleate, triglycerides such as olive oil, beef tallow, coconut oil, etc. , Fatty acids such as stearic acid, oleic acid, lithinolic acid, higher alcohols such as oleyl alcohol, stearyl alcohol, octyldodecanol, anionic surfactants such as sulfosuccinic acid ester and sodium polyoxyethylene alkyl sulfate, alkylbetaine salts, etc. Amphoteric surfactants, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, these polyoxyethylene adducts, polyoxyethylene alkyl ethers, poly Nonionic surfactants such as xylethylene fatty acid esters, polyhydric alcohols such as polyethylene glycol, glycerin and 1,3-butanediol, thickening / gelling agents, antioxidants, UV absorbers, colorants, preservatives , Powder and the like can be contained.

  In addition, when used as an external preparation for skin, it contains a component that suppresses inflammation, for example, non-steroidal anti-inflammatory agents such as indomethacin and bufexamac, anti-inflammatory herbal agents such as burdock root extract, birch extract and / or extracts thereof. Is also preferable.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

  In this experiment, animals that were given a mental stress load by overloading (dense breeding) were used to verify the effects of the adrenal hypertrophy inhibitor of the present invention on the influence (adrenal hypertrophy) caused by mental stress.

I. Experimental method <Animal used>
HOS: Hr-1 hairless mice (female, 7 weeks) were acclimated at a rate of 5 animals per cage, then were bred and used in the following 6 groups.
(1) Normal (normal group): 5 animals per cage, fed with a commercial feed and reared for 12 days (1 group).
(2) Stress (mental stress group): 20 animals per cage were fed for 12 days with a commercial feed (5 groups).

<Experimental procedure>
Experiments were started on experimental animal groups (6 groups) reared by the above rearing method. That is, a commercially available feed (manufacturer; Oriental Co., Ltd., trade name: ordinary feed “MF”) was fed into the above 6 groups (Food Intake) and bred for 7 days. However, 1 group out of the above (2) (mental stress load group: 5 groups) was fed a feed containing no specimen (Control). Another group was fed a feed mixed with a known antipsychotic, chlorpromazine hydrochloride (Positive Control). The remaining three groups were administered specimens (naringin and nariltin) in the amounts shown in Table 1 below. The specimens (naringin and nariltin) were prepared by pulverizing the peel of Unshu mandarin orange with 50% methanol after pulverizing the peel of Unshu mandarin and purifying the extract by HP-20 and silica gel column chromatography. Is.

II. Experimental Results Seven days after the start of the experiment, the adrenal weight was measured for each group of mice. The results are shown in Table 1.

  As can be seen from Table 1, the adrenal glands are enlarged (Control) when mental stress due to dense breeding is applied, but by giving Naringin or Nariltin, it is markedly higher than known antipsychotics (Chlorpromazine hydrochloride). It turns out that the superior adrenal hypertrophy suppression effect is exhibited.

  Thus, according to the result of Example 1, it turns out that the adrenal hypertrophy inhibitor of this invention has the outstanding inhibitory effect with respect to adrenal hypertrophy.

The adrenal hypertrophy inhibitor of the present invention is excellent in the action of suppressing adrenal hypertrophy associated with a decrease in the function of the secretory system of the living body due to mental stress.
Such an adrenal hypertrophy inhibitor of the present invention is contained in a large amount in citrus fruits or processed products thereof, and is gentle to the human body and high in safety. Therefore, by adding it to animal or seafood feeds, A safe feed composition that has the effect of suppressing the decline in productivity and quality caused by stress loading due to crowded breeding and that can prevent harmful effects on the human body taking it without depending on drugs such as chemicals and antibiotics Can be provided. Moreover, the composition for a highly safe human body which can suppress the adrenal hypertrophy which arises by various factors, such as a side effect of a steroid, can be provided by mix | blending with an oral administration agent and a skin external preparation.
In particular, since it is effective to use the peel or juice-pressed residue of Satsuma mandarin, it is expected to be useful for further effective use of Satsuma mandarin, which is an excellent agricultural product in Japan.

Claims (9)

  An adrenal hypertrophy inhibitor comprising, as an active ingredient, a flavone compound selected from the group consisting of nariltin and naringin or a salt thereof.   The adrenal hypertrophy inhibitor according to claim 1, wherein the adrenal hypertrophy occurs under dense breeding conditions.   A feed composition comprising the adrenal hypertrophy inhibitor according to claim 1 or 2.   The feed composition according to claim 3, wherein the feed composition is a feed for densely breeding animals or seafood.   The feed composition according to claim 3 or 4, wherein the source of the adrenal hypertrophy inhibitor is citrus peel or fruit juice press residue.   The feed composition according to claim 5, wherein the citrus fruit is selected from the group consisting of mandarin orange, ponkan, hassaku and navel orange.   A therapeutic composition comprising the adrenal hypertrophy inhibitor according to claim 1 or 2.   The therapeutic composition according to claim 7, wherein the base of the adrenal hypertrophy inhibitor is citrus peel or fruit juice press residue.   The therapeutic composition according to claim 8, wherein the citrus fruit is selected from the group consisting of mandarin orange, ponkan, hassaku and navel orange.