Ruminant insulin resistance inhibitor

Abstract

This insulin resistance inhibitor for ruminant animals is characterized by containing cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol and / or cardol.

Description

Technical Field

[0001] The present invention relates to an agent and a feed for suppressing insulin resistance in ruminants, and a method for suppressing insulin resistance using the same.

Background Art

[0002] When using ruminants as livestock, maintaining the health of livestock products and disease control are important factors for improving productivity. Insulin resistance refers to a state in which the action of insulin, such as promoting glucose uptake, decreases, and can cause diabetes, hyperlipidemia, etc. In particular, in periparturient ruminants, there is a risk that insulin resistance is likely to occur due to changes in energy metabolism and hormonal balance. However, almost no feed ingredients effective for suppressing insulin resistance in ruminants are known.

[0003] As effects of cashew nut shell oil on ruminants, an effect of improving rumen fermentation (Patent Document 1), an effect of controlling bloat (Patent Document 2), an effect of controlling coccidiosis (Patent Document 3), an effect of controlling acidosis (Patent Document 4), etc. are known. However, there has been no knowledge regarding suppression of insulin resistance in ruminants by cashew nut shell oil so far.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present invention aims to provide a material for suppressing insulin resistance in ruminants.

Means for Solving the Problems

[0006] As a result of intensive research to solve the above problems, the present inventors have found that insulin resistance can be suppressed by administering cashew nut shell liquid (hereinafter sometimes abbreviated as CNSL) to ruminants. Based on such findings, the present inventors have completed the present invention.

[0007] That is, the present invention is as follows. (1) An agent for suppressing insulin resistance in ruminants, characterized by containing cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol. (2) The insulin resistance suppressing agent according to (1), wherein the ruminant is a cow. (3) The insulin resistance suppressing agent according to (1) or (2), wherein the ruminant is a female ruminant. (4) The insulin resistance suppressing agent according to (3), wherein the female ruminant is a female ruminant from 30 days before parturition to 30 days after parturition. (5) The insulin resistance suppressing agent according to any one of (1) to (4), which has an effect of suppressing the insulin resistance index by 30% or more and reducing the concentration of free fatty acids and / or ketone bodies in the blood. (6) A feed for suppressing insulin resistance in ruminants, characterized by containing cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol. (7) The feed according to (6), wherein the crude protein (CP) content is 12% DM (% dry matter) or more. (8) The feed according to (6) or (7), wherein the neutral detergent fiber (NDF) content is 20% DM or more. (9)A method for suppressing insulin resistance, characterized by administering cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol to non-human animals. (10)A method for suppressing insulin resistance in ruminants, characterized by administering cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol to ruminants. (11)The method according to (10), wherein the ruminant is a cow. (12)The method according to (10) or (11), wherein the ruminant is a female ruminant. (13)The method according to (12), wherein cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol is administered at any time from 30 days before parturition to 30 days after parturition. (14)The method according to (12), wherein cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol is administered at any time from 30 days before parturition to the time of parturition. (15)The method according to any one of (10) to (14), wherein the administration period is at least 14 days. (16)The method according to any one of (10) to (15), wherein cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol is administered at 0.1 to 50 g / head / day. (17)Use of cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol for the manufacture of an agent for suppressing insulin resistance in ruminants. [Advantages of the Invention]

[0008] According to the present invention, by administering an agent or feed containing cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol to ruminants, insulin resistance can be suppressed. Thereby, the health state of ruminants can be maintained and the growth efficiency can be improved. [Modes for Carrying Out the Invention]

[0009] The insulin resistance inhibitor for ruminants of the present invention is characterized by containing cashew nut shell liquid (CNSL), heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol.

[0010] In the present invention, the suppression of insulin resistance means suppressing the state of falling into a state where insulin action such as glucose uptake promoting action is reduced. Insulin resistance can be evaluated by the following RQUIKI value, and it can be evaluated that the lower this value is, the higher the insulin resistance is. Therefore, if the decrease in the RQUIKI value can be suppressed by administering CNSL or the like as compared with the non-administered state, it can be said that insulin resistance has been suppressed. The index of insulin resistance such as the RQUIKI value is preferably suppressed by 30% or more, more preferably 50% or more by the administration of the insulin resistance inhibitor of the present invention as compared with the non-administered state.

[0011] RQUIKI = 1 / [Log(Glu)+Log(Insulin)+Log(NEFA)] Here, Glu, Insulin, and NEFA indicate the blood glucose concentration (mg / dL), insulin concentration (μU / mL), and free fatty acid concentration (mmol / L), respectively.

[0012] Cashew nut shell liquid is an oily liquid contained in the shell of the fruit of the cashew tree (Anacardium occidentale L.). Cashew nut shell liquid contains anacardic acid, cardanol, and cardol as its components. Anacardic acid is converted to cardanol by heat treatment, and it is also possible to use cashew nut shell liquid (heat-treated cashew nut shell liquid) that contains only cardanol and cardol by heat treatment.

[0013] Cashew nut shell oil (unheated), which is extracted by pressing cashew nut shells, contains 55 - 80% by mass of anacardic acid, 5 - 20% by mass of cardanol, and 5 - 30% by mass of cardol, as described in J. Agric. Food Chem. 2001, 49, 2548 - 2551. Heated cashew nut shell oil obtained by heat - treating unheated cashew nut shell oil (for example, at 70°C or higher, preferably 130°C or higher) has decarboxylated anacardic acid, which is the main component of unheated cashew nut shell oil, and is converted into cardanol, and contains 0 - 10% by mass of anacardic acid, 55 - 80% by mass of cardanol, and 5 - 30% by mass of cardol.

[0014] Cashew nut shell oil can be obtained as a vegetable oil extracted by pressing cashew nut shells. It can also be obtained by dry - distilling or solvent - extracting cashew nut shells. For example, cashew nut shell oil can also be obtained by the method described in JP - A - 8 - 231410. Commercially available products can also be used.

[0015] The insulin resistance inhibitor of the present invention may contain anacardic acid, cardanol, and / or cardol itself instead of cashew nut shell oil.

[0016] Examples of anacardic acid include natural anacardic acid, synthetic anacardic acid, and their derivatives. Commercially available anacardic acid may also be used. As described in JP - A - 8 - 231410, anacardic acid can be obtained by subjecting cashew nut oil obtained by extracting cashew nut shells with an organic solvent to elution using a mixed solvent of n - hexane, ethyl acetate, and acetic acid with a changed ratio, for example, using silica gel column chromatography (JP - A - 3 - 240721, JP - A - 3 - 240716, etc.).

[0017] Examples of cardanol include natural cardanol, synthetic cardanol, and their derivatives. In addition, the cardanol used in the present invention can be obtained by decarboxylating anacardic acid, which is the main component of cashew nut shell oil.

[0018] Examples of cardol include natural cardol, synthetic cardol, and their derivatives. In addition, the cardol used in the present invention can be obtained by purifying from cashew nut shell oil.

[0019] The content of cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol, and / or cardol in the insulin resistance inhibitor of the present invention is preferably 0.1% by mass to 100% by mass, more preferably 0.5% by mass to 95% by mass, and particularly preferably 1% by mass to 90% by mass based on the total amount of the agent.

[0020] As the insulin resistance inhibitor of the present invention, a stock solution of cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol, and / or cardol can also be directly administered orally.

[0021] On the other hand, the insulin resistance inhibitor of the present invention may contain, in addition to cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol, and / or cardol, components such as excipients that can be used in feeds or pharmaceuticals, such as lactose, sucrose, D-mannitol, α-starch, starch, corn starch, crystalline cellulose, bentonite, silica gel, and light anhydrous silicic acid.

[0022] In addition to cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol, the insulin resistance inhibitor of the present invention may further contain optional components such as components effective for promoting the growth of ruminants, nutritional supplement components, components for enhancing storage stability, coating agent components, and the like. Examples of such optional components include feed raw materials such as bran, alfalfa, and timothy, feed additives, food raw materials, food additives, pharmaceutical raw materials, and other supplement components used in animal supplements (hereinafter referred to as supplements). For example, probiotics such as Enterococcus bacteria, Bacillus bacteria, and Bifidobacterium; enzymes such as amylase and lipase; vitamins such as L-ascorbic acid, choline chloride, inositol, and folic acid; minerals such as potassium chloride, ferric citrate, magnesium oxide, and phosphates; amino acids such as DL-alanine, DL-methionine, and L-lysine; organic acids such as fumaric acid, butyric acid, lactic acid, and acetic acid and their salts; antioxidants such as ethoxyquin, dibutylhydroxytoluene, butylhydroxyanisole, ferulic acid, vitamin C, and vitamin E; mold inhibitors such as calcium propionate; binders such as carboxymethyl cellulose (CMC), sodium caseinate, and sodium polyacrylate; emulsifiers such as lecithin, glycerin fatty acid esters, and sorbitan fatty acid esters; pigments such as astaxanthin and canthaxanthin; and flavoring agents such as various esters, ethers, and ketones. The types of supplements and components other than cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol, and / or cardol are not particularly limited.

[0023] The insulin resistance inhibitor of the present invention may contain an oil absorbent such as magnesium oxide, stearate, talc, zeolite, diatomaceous earth, and silica, and the oil absorbent is preferably in particulate form. The oil absorbent is preferably an oil absorbent that adsorbs 50 to 300 g of oil per 100 g. Further, when the particle size exceeds 300 μm, the particles become coarse and separate, so those having a particle size of 2 to 300 μm are preferred. In one aspect of the insulin resistance inhibitor of the present invention, the preferred mass ratio of the oil absorbent to cashew nut shell liquid (CNSL), heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol is 100:20 to 100:180. Further, the preferred mass ratio in the case of the oil absorbent and the ground cashew nut product is 15:100 to 60:100.

[0024] The dosage form of the insulin resistance inhibitor of the present invention is not particularly limited, and examples thereof include any form such as a liquid preparation, a powder preparation, a solid, a tablet, a capsule preparation, an emulsion, a pellet preparation, a tablet, a coating agent, etc., but a liquid preparation, a powder preparation, a capsule preparation, a pellet preparation, and a tablet are preferred. As the liquid preparation, cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol may be used as they are, or cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol may be dissolved in a solvent such as ethanol, or the above excipient or optional component may be added and used. Further, the following powder preparations, capsule preparations, pellet preparations, and tablet preparations may be suspended or floated in a liquid. As the powder preparation, the above excipient may be added to cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol and powdered. As the capsule preparation, cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol may be directly filled into capsules, or the above excipient or optional component may be added. As the pellet preparation, the above excipient may be added to cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol, granulated, and pelletized. As the tablet preparation, the above excipient may be added to cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol, granulated, and tableted. In addition, when containing an oil absorbent such as silica, it is preferably formulated as a powder preparation, a tablet preparation, or a pellet preparation.

[0025] As described above, the insulin resistance inhibitor of the present invention can be produced by mixing cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol and, if necessary, an excipient or optional components and formulating them. Depending on the form of the agent, the pulverized or crushed product of the above-mentioned cashew nut shell, or the cashew nut shell without any treatment can be directly mixed with other optional components to obtain the insulin resistance inhibitor of the present invention. Furthermore, without mixing with other optional components, the pulverized or crushed product itself or the cashew nut shell itself can be used as the insulin resistance inhibitor.

[0026] The feed of the present invention is characterized by containing cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol. The content of cashew nut shell liquid, heat-treated cashew nut shell liquid, anacardic acid, cardanol and / or cardol in the feed of the present invention is preferably 0.5 to 500,000 mass ppm, more preferably 5 to 300,000 mass ppm, and particularly preferably 50 to 100,000 mass ppm on a total amount basis per dry matter mass of the feed. If it is 0.5 mass ppm or more, an insulin resistance inhibitory effect can be expected. If it is 5 mass ppm or more, particularly preferably 50 mass ppm or more, the tendency becomes remarkable and is preferable. On the other hand, although insulin resistance inhibition can be exhibited even at 500,000 mass ppm, 300,000 mass ppm or less, particularly preferably 100,000 mass ppm or less is preferable. The feed of the present invention preferably has a crude protein (CP) content of 12% DM (% dry matter) or more, more preferably 15% DM or more, and still more preferably 17% DM or more. The upper limit of the CP content is, for example, 30% DM. The CP content can be measured by the Kjeldahl method (wet analysis). The feed of the present invention preferably has a neutral detergent fiber (NDF) content of 20% DM or more, more preferably 25% DM or more, and still more preferably 30% DM or more. The upper limit of the NDF content is, for example, 50% DM. The NDF content can be measured by the detergent analysis method (wet analysis). The analytical methods for CP and NDF are also described in Feed Analysis and Explanation 2004 (Japan Scientific Feed Association, March 2004). In the feed of the present invention containing cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol and / or cardol, by increasing the protein and neutral detergent fiber contents, especially in female ruminants before and after parturition, the insulin resistance inhibitory effect can be synergistically enhanced while maintaining the health status.

[0027] The feed of the present invention can be produced by adding and mixing the cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol and / or cardol or the insulin resistance inhibitor of the present invention containing the same to the feed components. At this time, when using a powdery or solid agent, in order to facilitate mixing, a liquid carrier can be used to make the agent in a liquid or gel form. In this case, a fluid liquid such as water, vegetable oil, liquid animal oil, mineral oil, synthetic oil, water-soluble polymer compound, etc. can be used as the liquid carrier. Also, in order to maintain the uniformity of cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol and / or cardol in the feed, it is also preferable to blend water-soluble polysaccharides such as alginic acid, sodium alginate, xanthan gum, carboxymethyl cellulose, α-starch, sodium caseinate, gum arabic, guar gum, tamarind seed polysaccharide, etc.

[0028] In the feed of the present invention, the types and blending ratios of feed ingredients blended with the agent of the present invention are not particularly limited, and any feed that has been conventionally fed to each animal may be used. For example, it can be prepared using corn grains, corn flour, milo, bran, soybean meal, barley, wheat flour shorts, wheat middlings, alfalfa, timothy, clover, defatted rice bran, northern meal, coastal meal, yeast, molasses, meat pieces, bone meal, calcium carbonate, dicalcium phosphate, yellow grease, vitamins, minerals, and the like.

[0029] The types of ruminants to which the insulin resistance inhibitor or feed of the present invention is administered are not particularly limited. Examples include ruminants such as cows, water buffalo, goats, sheep, and yaks. Among them, it is particularly suitable to administer to cows, and preferred cow breeds include female Holstein, Jersey, Japanese Black, Japanese Shorthorn, and Aberdeen Angus. The amount of the insulin resistance inhibitor or feed to be administered can be appropriately adjusted according to the type, body weight, age, sex, health status, and feed components of the animal. At this time, the amount of cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol, and / or cardol contained in the feed is, for example, 0.01 to 500 g / head / day, preferably 0.1 to 200 g / head / day, more preferably 0.1 to 50 g / head / day, and even more preferably 0.5 to 5 g / head / day. In addition, since the body weight range of cows to which the insulin resistance inhibitor or feed of the present invention is administered is usually 500 to 900 kg, the amount of cashew nut shell oil, heat-treated cashew nut shell oil, anacardic acid, cardanol, and / or cardol contained in the feed given per day per 1 kg of the cow's body weight is 0.000011 g to 1 g, preferably 0.00011 g to 0.4 g, and more preferably 0.0011 g to 0.2 g.

[0030] The administration timing of the insulin resistance inhibitor or feed of the present invention is not particularly limited. In the case of dairy cows, it is preferably administered to dairy cows at a monthly age suitable for milk production (usually 20 to 144 months old, preferably 20 to 132 months old, more preferably 20 to 108 months old). Furthermore, the insulin resistance-suppressing feed of the present invention is preferably administered to periparturient ruminants, preferably ruminants in the transition period. For example, it can be administered at any time from 60 days before parturition to 30 days after parturition, preferably from 30 days before parturition to 30 days after parturition, more preferably from 14 days before parturition to 14 days after parturition. In particular, in order to suppress insulin resistance caused by parturition, it is preferably administered from before parturition, for example, it can be administered at any time from 60 days before parturition to parturition, preferably from 30 days before parturition to parturition, more preferably from 14 days before parturition to parturition. In this case, it may be administered from before parturition to after parturition. The administration period is not particularly limited, but is preferably 14 days or more, more preferably 30 days or more, and even more preferably 60 days or more.

Examples

[0031] Hereinafter, the present invention will be specifically described with reference to examples. However, the aspects of the present invention are not limited to the following examples.

[0032] Evaluation of insulin resistance-suppressing effect In the test, a total of 9 cows, including 5 cows in the control group and 4 cows in the administration group, were used. The administration group was fed a feed containing 5.0 g of cashew nut shell oil (containing 61.8% by mass of anacardic acid, 8.2% by mass of cardanol, and 19.9% by mass of cardol) from 14 days before parturition. The crude protein (CP) content in the feed was 12% DM or more, and the neutral detergent fiber (NDF) content was 20% DM or more. The test cows were female Holstein adult cows (average age 57.5 months, range 25 months to 90 months), overweight cows with a body condition score (BCS) indicating fatness of 3.5 to 4.0, and individuals with a high risk of acquiring insulin resistance.

[0033] Blood samples were collected 14 days before parturition, 3 days and 7 days after parturition, and items related to insulin resistance and items related to inflammation in the body were measured. The results are shown in Table 1.

[0034]

Table 1

[0035] <Results and Discussion> In the measured values, differences were observed on the 3rd day after childbirth, and it was revealed that the RQUIKI value indicating insulin resistance was significantly higher in the administered group, indicating no insulin resistance.

Claims

1. An inhibitor for suppressing insulin resistance in female ruminants from 30 days before parturition to 30 days after parturition, characterized by containing cashew nut shell oil.

2. The insulin resistance inhibitor according to Claim 1, wherein the ruminant is a cow.

3. The insulin resistance inhibitor according to any one of Claims 1 to 2, which has an effect of suppressing an insulin resistance index by 30% or more and reducing the concentration of free fatty acids and / or ketone bodies in the blood.

4. A feed for suppressing insulin resistance in female ruminants from 30 days before parturition to 30 days after parturition, characterized by containing cashew nut shell oil.

5. The feed according to Claim 4, wherein the crude protein (CP) content is 12% DM (% dry matter) or more.

6. The feed according to Claim 4 or 5, wherein the neutral detergent fiber (NDF) content is 20% DM or more. feed.

7. A method for suppressing insulin resistance in female ruminants, characterized by administering cashew nut shell oil to female ruminants at any time from 30 days before parturition to 30 days after parturition.

8. The method according to Claim 7, wherein the ruminant is a cow.

9. The method according to Claim 7 or 8, wherein cashew nut shell oil is administered at any time from 30 days before parturition to the time of parturition.

10. The method according to any one of Claims 7 to 9, wherein the administration period is at least 14 days.

11. The method according to any one of Claims 7 to 10, wherein 0.1 to 50 g / head / day of cashew nut shell oil is administered.

12. Use of cashew nut shell oil for the manufacture of an inhibitor for suppressing insulin resistance in female ruminants from 30 days before parturition to 30 days after parturition.

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