JP2013043850A - Lipolysis promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a lipolysis promoter comprising two ingredients of lactoferrin and another ingredient as active ingredients, and having a sufficient visceral fat decomposition promoting action superior to the action of each single ingredient.SOLUTION: There are provided: a lipolysis promoter comprising lactoferrin and hop extracts as active ingredients; the lipolysis promoter whose hop extracts include at least one selected from the group consisting of a hop extract iso-α acid fraction, a hop extract β acid fraction, and a hop extract xanthohumol fraction; a lipolysis promoting composition containing the lipolysis promoter; the lipolysis promoter or the lipolysis promoting composition in a form of food, feed or medicine; a method of imparting lipolysis promoting effect to the food or the feed by adding the lactoferrin and the hop extracts to the food or the feed; and the method wherein the hop extracts contain at least one selected from the group consisting of the hop extract iso-α acid fraction, the hop extract β acid fraction, and the hop extract xanthohumol fraction.

Description

  The present invention relates to a lipolysis promoter.

  In modern society, nutrient intake is chronically high and fat tends to accumulate in the body due to lack of exercise. In particular, visceral fat is a tissue that secretes bad adipocytokines that increase the risk of hypertension, hyperglycemia, hyperlipidemia and the like. Therefore, development of components useful for reducing visceral fat without difficulty is underway. For example, exerting an effect by ingesting catechins with exercise (Non-Patent Document 1), polyphenols suppress fat absorption (Non-Patent Document 2), hop extract is a treatment for obesity and weight gain, There are reports such as being useful for prevention and improvement (Patent Documents 1 and 2).

  It is known that lactoferrin exerts a fat reduction promoting effect when combined with a blood circulation promoter (Patent Document 3).

International Publication No. 2003/068205 Specification JP 2006-306800 A JP 2008-69121 A

International Journal of Obesi Pharmacology and treatment 32 (6), 335-342 (2004)

  However, the visceral fat reduction effect by each of catechin alone, polyphenol alone, hop extract alone, and a combination of lactoferrin and a blood circulation promoter was not sufficient.

  An object of the present invention is to provide a lipolysis accelerator comprising lactoferrin and other components, each having a sufficient visceral lipolysis promoting action that exceeds the action of each alone.

The present invention provides the following inventions.
[1] A lipolysis promoter comprising lactoferrin and hop extract as active ingredients.
[2] The above [1], wherein the hop extract contains at least one selected from the group consisting of a hop extract iso-α acid fraction, a hop extract β-acid fraction, and a hop extract xanthohumol fraction. The lipolysis promoter as described.
[3] A lipolysis-promoting composition comprising the lipolysis accelerator according to [1] or [2].
[4] The lipolysis promoter according to [1] or [2] or the lipolysis promotion composition according to [3], which is in the form of food, feed, or medicine.
[5] A method in which lactoferrin and a hop extract are added to food or feed to impart an effect of promoting lipolysis to the food or feed.
[6] The above [5], wherein the hop extract contains at least one selected from the group consisting of a hop extract iso-α acid fraction, a hop extract β-acid fraction, and a hop extract xanthohumol fraction. A method for imparting a lipolysis-promoting effect to the described food or feed.

  The lipolysis promoter of the present invention not only exceeds the lipolysis-promoting effect of lactoferrin alone and the lipolysis-promoting effect of hop extract alone, but is not only an additive effect of these effects, but also an unexpected synergistic effect It is useful for various uses such as foods, feeds, and pharmaceuticals.

The lipolysis promoter of the present invention contains lactoferrin and hop extract as active ingredients.

  Examples of lactoferrin include commercially available lactoferrin; mammals (eg, humans, cows, sheep, goats, horses, etc.) colostrum, transitional milk, regular milk, end milk, etc. or processed milk products of skim milk, whey, etc. And lactoferrin separated by a conventional method (for example, ion exchange chromatography); lactoferrin produced from plants (tomato, rice, tobacco); lactoferrin obtained by genetic recombination. Lactoferrin may be a commercially available product or can be prepared and used by a known method.

  As the lactoferrin, one of the above specific examples may be used alone, or two or more may be used in appropriate combination. In addition, as lactoferrin, the lactoferrin derived from a cow is preferable.

  The blended amount of lactoferrin in the lipolysis accelerator of the present invention is usually 5 mg to 5,000 mg / day, preferably 50 mg to 1,000 mg / day, more preferably as the daily human intake. 100 mg to 500 mg / day. By being in this range, a lipolysis promoter having a significantly excellent lipolysis promoting effect can be obtained. Moreover, it is preferable also in terms of the cost and safety of the agent.

  A hop extract is a component extracted from all or part of a hop plant. Hops are perennials (scientific name Humulus lupulus) that are classified in the family of Lingaceae native to Europe, and are generally called hops referring to the fruits (mature female flowers). Although there is no limitation in the extraction site | part of the hop plant body, it is preferable that it is a part containing a fruit or a fruit. The hop plant may be subjected to extraction part advance compression and crushing. Examples of the extraction method include a solvent extraction method and a supercritical carbon dioxide extraction method. Examples of the solvent include water, alcohols (lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, and butanol), lower alkyl esters such as ethyl acetate, ethylene glycol, butylene glycol, propylene glycol, and glycerin. Examples include glycols, polar solvents such as acetone and acetic acid, hydrocarbons such as benzene and hexane, ethers such as ethyl ether and petroleum ether, and the like. After performing extraction with a solvent or supercritical carbon dioxide, a concentration treatment such as filtration or reduced pressure may be performed as necessary.

  As the hop extract, the fraction extracted from the hop plant as described above (solvent hop extract) can be used as it is, but the hop extract is obtained by subjecting the hop crude extract to a purification treatment. Minutes may be used. Examples of such a fraction include a hop extract iso-α acid fraction, a hop extract β-acid fraction, and a hop extract xanthohumol fraction. The hop extract iso-alpha acid fraction is a fraction containing, as a main component, an iso-alpha acid (for example, isohumulone, isocohumulone, isoadhumulone, etc.) or a derivative thereof among the hop extract. The hop extract β-acid fraction contains, as a main component, a β-acid (a compound of formula (I) of Patent Document 1 (International Publication No. 2003/068205), for example, luprones or a derivative thereof) among hop extracts. It is a fraction to be. A hop extract xanthohumol fraction is a fraction which has xanthohumol as a main component among hop extracts. Further, the hop crude extract or α acid fraction may be heated in the presence of an alkali or magnesium oxide and further isomerized to obtain a high content of iso α acid. These may be used alone, in combination of two or more, or may be used in combination with a hop crude extract. Examples of the purification treatment for obtaining the hop extract iso-α acid fraction, the hop extract β-acid fraction, and the hop extract xanthohumol fraction include high-performance liquid chromatography. Moreover, a commercial item can also be used for each extract of a hop crude extract, a hop extract iso alpha acid fraction, a hop extract beta acid fraction, and a hop extract xanthohumol fraction. For example, the crude hop extract can be obtained from Maruzen Pharmaceutical Co., Ltd. The hop extract iso-α acid fraction, the hop extract β-acid fraction, and the hop extract xanthohumol fraction can be obtained from Hopsteiner, respectively.

  The hop extract may contain one or more selected from the group consisting of hop extract iso-α acid fraction, hop extract β-acid fraction, and hop extract xanthohumol fraction extract. Preferably, the hop extract β-acid fraction alone or a combination of two or more hop extracts containing the hop extract β-acid fraction is more preferable.

  The compounding amount of the hop extract is usually 0.1 mg to 5,000 mg / day, desirably 1 mg to 500 mg / day, and more desirably 10 mg to 50 mg / day as a human intake per day. day. By being in this range, a lipolysis promoter having a significantly excellent lipolysis promoting effect can be obtained. In addition, there is no problem in terms of the cost and safety of the agent.

  The blending ratio of lactoferrin and hop extract is usually 50000: 1 to 1: 1000, preferably 1000: 1 to 1: 100, more preferably 50: 1 to 1 as human intake per day. 1: 1 and even more desirably 50: 1 to 3: 1. By being in this range, a lipolysis promoter having a significantly excellent lipolysis promoting effect can be obtained.

  The lipolysis promoter of the present invention promotes fat degradation. In the present invention, “facilitating fat degradation” means that the degree (rate, amount, etc.) of fat degradation in the living body is increased more than usual.

  Confirmation that the lipolysis promoter of the present invention promotes the degradation of fat can be performed, for example, as in the Examples. That is, a sample is added to preadipocytes prepared from rat mesenteric adipose tissue, and glycerol is quantified. Commercially available kits such as F-kit glycerol (Roche, product number: 14820) may be used for quantification. When the amount of glycerol obtained is large compared to the amount of glycerol when no sample is added, it can be confirmed that fat decomposition has been promoted.

  The target of the lipolysis promoter of the present invention is not particularly limited. Useful for humans or non-human vertebrates. Further, the health condition of the target human or non-human vertebrate is not particularly limited.

  In the lipolysis promoter of the present invention, lactoferrin and hop extract as active ingredients can be blended with a pharmaceutically acceptable carrier. Examples of the pharmaceutically acceptable carrier include oily components, lubricants, excipients, binders, disintegrants and the like. Further, an appropriate amount of additives such as a sweetening agent, a sour agent, a flavoring agent, a coloring agent, and a pigment may be appropriately contained.

  Examples of the oil component include various fatty acid esters, hydrocarbons, higher fatty acids, higher alcohols and the like. Examples of the lubricant include magnesium stearate, stearic acid, sodium stearyl fumarate, sucrose fatty acid ester, polyethylene glycol (macrogol), talc and the like.

  As binders, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, gelatin, starch, dextrin, gum arabic, sodium alginate, tragacanth, purified gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl alcohol (partially saponified product), ethyl cellulose, pullulan, Examples thereof include polyethylene glycol (macrogol).

  Disintegrants include carboxymethylcellulose calcium (carmellose calcium), carboxymethylcellulose sodium (carmellose sodium), low-substituted hydroxypropylcellulose, carboxymethylcellulose, carboxymethylstarch sodium, crosslinked carboxymethylcellulose sodium (croscarmellose sodium), Examples thereof include powdered cellulose, cellulose or derivatives thereof, cross-linked polyvinyl pyrrolidone (crospopidone), starch, carboxymethyl starch, hydroxypropyl starch, agar and the like.

Excipients are exemplified as follows:
Polysaccharides such as crystalline cellulose, sodium alginate, xanthan gum;
Starches such as pregelatinized starch, hydroxypropyl starch, corn starch, potato starch and derivatives thereof;
Sugars and sugar alcohols such as sucrose, glucose, xylitol, erythritol, sorbitol, lactitol, trehalose, palatinose, palatinit (reduced palatinose), mannitol, maltitol, lactitol, lactose, fructose, powdered reduced maltose varicella;
Cellulose such as powdered cellulose, partially pregelatinized starch, ethylcellulose and derivatives thereof;
Light anhydrous silicic acid, titanium oxide, aluminum hydroxide gel, synthetic aluminum silicate, aluminum trisilicate, silicon dioxide, kaolin, cocoa butter, citric acid or its salt, stearic acid or its salt, calcium hydrogen phosphate, phosphoric acid Sodium hydride.

  Examples of the sweetener include aspartame, acesulfame potassium, saccharin sodium, sucralose, stevia, thaumatin and the like. Examples of the sour agent include citric acid, succinic acid, tartaric acid, malic acid, fumaric acid and the like. Examples of the flavoring agent include monoterpenes such as menthol, camphor, borneol, limonene, and various fragrances.

  The dosage form of the lipolysis promoter of the present invention is not particularly limited, and can be appropriately selected depending on the dosage form. In the case of oral administration, tablets, capsules, granules, powders, fine granules, syrups, sustained-release tablets, tablets, chewable tablets, drop agents and the like can be mentioned.

  The method for producing the lipolysis promoter is not particularly limited, and can be appropriately selected according to the dosage form. For example, when the dosage form is a tablet, a method of obtaining a tablet by mixing lactoferrin and optional components that can be blended as necessary, and then compressing the mixture to obtain a tablet, and further, the tablet obtained after compression molding as described above is enteric. Examples include a method of coating with components (method of enteric solvent), and the latter method is preferred. Examples of the enteric component include shellac, hydroxymethylcellulose phthalate, carboxymethylcellulose, aminoalkyl methacrylate copolymer, brewer's yeast cell wall (for example, trade name yeast wrap), tapioca starch, gelatin, pectin, etc. Among them, shellac is preferable. Whether or not it is an enteric solvent can be confirmed by the 14th revised Japanese Pharmacopoeia Disintegration Test Method.

  The lipolysis promoter of the present invention exhibits an excellent promoting effect on fat degradation. Therefore, it is effective for the prevention and treatment of obesity. According to the lipolysis promoter of the present invention, it is expected that visceral fat can be reduced, so that prevention and treatment of lifestyle-related diseases such as hypertension, hyperglycemia and hyperlipidemia can be efficiently achieved. Is done.

  The administration method can be appropriately determined depending on the blending concentration of the polyphenol and hop extract, the dosage form, the age, weight, sex, and the exercise load when taking before exercise. For example, when the dosage form is a tablet, it is preferably taken with water or the like. The administration interval can be determined as appropriate, and may be any time before a meal, after a meal, or between meals.

  In addition to the administration of the lipolysis promoter of the present invention, administration of other lipolysis promoter or composition may be combined. Or the lipolysis which combined the lipolysis promoter of this invention, and the lipolysis promoter other than the lipolysis promoter of this invention, or a lipolysis promotion composition which uses the combination of a lactoferrin and a hop extract as an active ingredient. It may be an accelerating composition.

  By providing a lipolysis promoter or a lipolysis-promoting composition to humans or non-human vertebrates, fat degradation can be promoted. Therefore, the lipolysis promoter or lipolysis promoter composition of the present invention is also useful as a medicine, quasi drug, food, or feed.

  Foods are usually processed foods, and include so-called health foods as well as functional foods, health functional foods, foods for specified health use, nutritional functional foods, and nutritional supplements.

  Here, the intake time of the food containing the lipolysis promoter or the lipolysis promoter composition is not particularly limited. For example, it can be taken before and after a meal or before and after exercise.

  In the case of food, it is preferable to display the effect of the present invention. As an indication of the effect of the present invention, for example, an indication that it is used for promoting the decomposition of fat may be mentioned.

  Thus, the lipolysis promoter or lipolysis promoter composition of the present invention promotes the degradation of fat in the body by being administered to humans as a food and ingested. Therefore, the food of the present invention is useful as various foods for preventing obesity.

  The lipolysis promoter or lipolysis promoter composition of the present invention is also useful as a feed because it can be expected to promote the degradation of fat in the body even when administered to vertebrates other than humans (eg, pets). is there.

  Furthermore, the lactoferrin and hop extract of the lipolysis promoter or lipolysis promoter composition of the present invention can impart a lipolysis promoting effect to the food or feed by adding it to normal food or feed. .

  Hereinafter, the present invention will be described in detail based on examples. Note that the present invention is not limited to the embodiments.

Experimental Examples 1-4 and Comparative Experimental Examples 1-4
A single evaluation of each sample shown in Table 1 and a composite evaluation with lactoferrin (excluding Comparative Experimental Example 1) were performed. The concentration of each sample in the single evaluation is 10 ppm, 3 ppm, and 1 ppm, and the concentration in the composite evaluation is a combination of 10 ppm of lactoferrin and 10 ppm of each sample, a combination of 10 ppm of lactoferrin and 3 ppm of each sample, a combination of 10 ppm of lactoferrin and 1 ppm of each sample, and lactoferrin A combination of 1 ppm and 10 ppm of each sample, a combination of 1 ppm of lactoferrin and 3 ppm of each sample, and a combination of 1 ppm of lactoferrin and 1 ppm of each sample.

Sample preparation Among the samples, lactoferrin is manufactured by Friesland Campina Domo, ginger extract is manufactured by Nippon Powdery Chemical Co., Ltd., epigallocatechin gallate is manufactured by Wako Pure Chemical Industries, Ltd. Using.
The concentration of each sample was adjusted by dissolving in water or DMSO.

As the crude hop extract, Maruzen Pharmaceutical Co., Ltd., the hop extract iso-α acid fraction, the hop extract β-acid fraction, and the hop extract xanthohumol fraction were manufactured by Hopsteiner.
The concentration of each sample was adjusted by dissolving in water or DMSO.

  Mesenteric adipose tissue was removed from the rat, blood and hair were washed with physiological saline supplemented with antibiotics, and the tissue was shredded. The tissue was dispersed by incubation with a solution containing collagenase. After filtering the undissolved tissue with a cell strainer, DMEM medium was added to lower the viscosity, and centrifugation was performed.

The obtained progenitor cells were washed, and then gently suspended in a visceral fat differentiation medium (Viscal Adipocyte Culture Medium, manufactured by Primary Cell Co., Ltd., code: VACMR). The cell was adjusted to 6 × 10 ⁶ cells / 24 well and cultured at 500 μL / well. Six days after the start of the culture, after confirming that fat cells had accumulated fat droplets, the medium was replaced with a medium containing various samples. The culture supernatant was collected 48 hours after the medium was changed, and the culture was terminated. All cultures were visually confirmed to be non-cytotoxic.

  In the primary culture of preadipocytes, Shimizu K, Sakai M, Ando M et al. (2006) Newly developed primary culture of rat visual adipocytes and ther in vitro characturistics. Cell Biol Int 30, 381-388 and JP-A-2005-328806 were referred to.

  The amount of fat decomposed was determined by quantifying glycerol in the culture supernatant. Glycerol was quantified using F-kit glycerol (Roche, product number: 14820). Absorbance was measured with Novaspec Plus (manufactured by GE Healthcare). The value of the effect of the added group was expressed as a relative value when the amount of glycerol in the non-added group was 0%.

  In measuring the amount of fat degradation by glycerol quantification of the culture supernatant of adipocytes, Okazaki H, Igarashi M, Nishi M et al. (2006) Identification of a novel member of the carboxylic esterase family that hydrates triacylycerol: a potential role in adiposity. Diabetes. 55, 2091-7. Referred to.

  As shown in Table 1, the lipolysis acceleration rate in the composite evaluation of Experimental Example 1 (+ lactoferrin 10 ppm) not only exceeds the lipolysis acceleration rate in the single evaluation, but also the fat in the single evaluation of 10 ppm of lactoferrin in Comparative Experimental Example 1 It also exceeded the numerical value obtained by adding the lipolysis acceleration rate (addition amount 10 ppm) in the independent evaluation of Experimental Example 1 to the decomposition acceleration rate. The same applies to Experimental Example 2, Experimental Example 3, and Experimental Example 4. Similarly, the lipolysis promotion rate in the combined evaluation of Experimental Examples 1 to 4 (+ lactoferrin 1 ppm) not only exceeds the lipolysis promotion rate in the single evaluation, but also the lipolysis promotion rate in the single evaluation of 10 ppm of lactoferrin in Comparative Experimental Example 1. Furthermore, the numerical value obtained by adding the lipolysis promotion rate in the independent evaluation (addition amount 1 ppm) of Experimental Examples 1 to 4 was also exceeded. This result shows that in the present invention, the combination of lactoferrin and a hop extract exhibits a remarkable synergistic effect that is unexpected and unexpected from the effect of promoting lipolysis by lactoferrin alone or the hop extract alone.

  Among the experimental examples 1 to 4, the result (132.7%) of the combined evaluation of lactoferrin (concentration 10 ppm) and the hop extract β-acid fraction (concentration 10 ppm) in the experimental example 3 is the hop extract β-acid fraction ( Not only is it more than twice the result (60.98%) of the single evaluation (concentration 10 ppm), but also the result of lactoferrin (concentration 10 ppm) in Experimental Example 1 (12.98%) (12.98%). 1%) was significantly higher. This result shows that the combination of lactoferrin and hop extract β-acid fraction exhibits a particularly remarkable synergistic effect in the present invention.

  The lipolysis promotion rate in the composite evaluation of Comparative Experimental Example 2 was lower than that of the composite evaluation of Experimental Examples 1 to 4. Moreover, it was lower than the numerical value which added the lipolysis acceleration rate of the lactoferrin independent evaluation of the comparative experiment example 1, and the lipolysis acceleration rate of the independent evaluation of the comparative experiment example 2. It is known that ginger extract exhibits a lipolysis promoting action. However, this result indicates that in this experimental system, ginger extract alone has a low lipolysis-promoting action, and a synergistic effect cannot be obtained even when ginger extract and lactoferrin are used in combination.

  In Comparative Experimental Examples 3 and 4, as in Comparative Experimental Example 2, the lipolysis promotion rate was low compared to the combined evaluation in Experimental Examples 1 to 4, and therefore, epigallocatechin gallate, which is one type of green tea polyphenol, Chlorogenic acid, which is a kind of coffee polyphenol, also has a low lipolysis promoting action alone in this experimental system, and it shows that a synergistic effect cannot be obtained even when used in combination with lactoferrin.

Experimental Examples 5 to 8 [Lipolysis promotion rate when two or more hop extracts are used]
Using each sample shown in Table 2, composite evaluation was performed in the same manner as in Experimental Example 1. The results are shown in Table 2.

  From Table 2, it is clear that: Since all of the evaluation results of Experimental Examples 5 to 8 exceeded 90, it can be seen that, in the present invention, a remarkable effect of promoting lipolysis is also exhibited by combining two or more hop extracts with lactoferrin. . Among them, since Experimental Examples 5, 7, and 8 exceeded 100, in the present invention, by including the hop extract β-acid fraction as the hop extract, a more remarkable lipolysis acceleration rate can be obtained. I understand.

Claims (6)

  A lipolysis promoter comprising lactoferrin and hop extract as active ingredients.   The lipolysis according to claim 1, wherein the hop extract contains one or more selected from the group consisting of a hop extract iso-α acid fraction, a hop extract β-acid fraction, and a hop extract xanthohumol fraction. Accelerator.   A lipolysis-promoting composition comprising the lipolysis promoter according to claim 1 or 2.   The lipolysis promoter according to claim 1 or 2, or the lipolysis promoter composition according to claim 3, which is in the form of food, feed or medicine.   A method of adding lactoferrin and a hop extract to a food or feed to impart an effect of promoting lipolysis to the food or feed.   The food according to claim 5, wherein the hop extract contains at least one selected from the group consisting of a hop extract iso-α acid fraction, a hop extract β-acid fraction, and a hop extract xanthohumol fraction. A method of imparting a lipolysis promoting effect to feed.