JP2020043850A - Antiobestic composition - Google Patents

Abstract

To provide a novel antiobestic composition, an obesity gene expression modifier (a steatogenesis gene expression inhibitor, a fat combustion gene expression promoter), a fatty acid synthetase activity inhibitor, and a carnitine palmitoyl transferase activity promoter.SOLUTION: There is provided an antiobestic composition containing a calcareous alga and/or a globin proteolysate as an active ingredient. The calcareous alga is a red alga and contains 0.1 to 60 wt.% of calcium and 0.01 to 10 wt.% of magnesium. A globin proteolysate contains 0.01 to 10 wt% of a tetrapeptide VVYP.EFFECT: The antiobestic composition has an action of reducing the expression amount of the steatogenesis gene and an action of increasing the expression amount of the fat combustion gene.SELECTED DRAWING: None

Description

  The present invention relates to an antiobesity composition containing a calcareous algae and / or a globin protein hydrolyzate as an active ingredient, an obesity gene expression regulator (lipogenesis gene transcription inhibitor, fat burning gene transcription promoter), and fatty acid synthase activity. And a carnitine palmitoyltransferase activity promoter.

  Obesity is one of the major problems in modern society, and its main factor is the increase in the intake of high-fat diets accompanying the westernization of Japanese lifestyle. To prevent obesity, it is effective to reduce calorie intake by restricting diet.However, this method requires strict nutritional guidance and lifestyle management, and it is not easy to implement in daily life. Not always. In addition, taking an artificially synthesized appetite suppressant or the like for a long period of time to prevent or improve obesity is not preferable because unexpected side effects may occur.

  Patent Literature 1 discloses that lime algae has a property of fixing calcium around cells like an armor, and that the lime algae contains proteins and lipids (particularly highly unsaturated EPA, DHA, etc.). Fatty acids), carbohydrates, vitamins, minerals other than calcium, and the like are described as being abundant.

  Patent Document 2 discloses that the globin proteolyte is a peptide mixture obtained by enzymatically decomposing globin protein, and that valine-valine-tyrosine-proline (VVYP) contained in this globin proteolyte It is described that the peptide has a fat absorption inhibitory action.

JP-A-08-33463 JP-A-09-256598

  The problem to be solved by the present invention is a novel anti-obesity composition, an obesity gene expression regulator (lipogenesis gene expression inhibitor, fat burning gene expression promoter), fatty acid synthase activity inhibitor, carnitine palmitoyltransferase activity The purpose is to provide an accelerator.

  The present inventors have conducted intensive studies, and as a result, have found that a globin proteolysate suppresses the expression of a fat synthesis gene. In addition, they found that lime algae suppressed the expression of a fat synthesis gene and promoted the expression of a fat burning gene. Furthermore, they found that the effect was enhanced by using a globin-decomposing protein and a lime algae in combination, and completed the present invention.

The present invention relates to the following.
[1] An anti-obesity composition comprising a lime algae and / or a globin protein hydrolyzate as an active ingredient.
[2] The anti-obesity composition according to [1], wherein the lime algae is a red algae.
[3] The anti-obesity composition according to [1] or [2], wherein the lime algae contains 0.1 to 60% by weight of calcium.
[4] The anti-obesity composition according to any one of [1] to [3], wherein the lime algae contains 0.01 to 10% by weight of magnesium.
[5] The anti-obesity composition according to any one of [1] to [4], wherein the globin protein hydrolyzate contains 0.01 to 10% by weight of the tetrapeptide VVYP.
[6] The anti-obesity composition according to any one of [1] to [5], which has an effect of reducing the expression level of a lipogenic gene.
[7] The anti-obesity composition according to any one of [1] to [6], which has an effect of increasing the expression level of a fat burning gene.
[8] The anti-obesity composition according to any one of [1] to [7], which is a food or drink, a functionally labeled food, a food for specified health use, a nutritionally functional food, a cosmetic, a quasi-drug, or a pharmaceutical. .

  According to the present invention, a novel anti-obesity composition can be provided. The anti-obesity composition of the present invention is useful for preventing and / or improving obesity by reducing the expression level of a fat synthesis gene and / or increasing the expression level of a fat burning gene.

It is a figure which shows the expression level of a fat synthesis gene. It is a figure which shows the expression level of a fat burning gene. It is a figure which shows the influence which the treatment with a lime algae and / or a globin protein hydrolyzate has on the amount of neutral fat in a cell. It is a figure which shows the body weight change by ingestion of lime algae and a globin protein decomposition product.

  Hereinafter, the present invention will be described in detail.

  One embodiment of the present invention is an anti-obesity composition containing lime algae as an active ingredient.

<Lime algae>
In the present invention, lime algae refers to algae that secrete or deposit lime substances on cell walls, and include, for example, red algae, green algae, cyanobacteria, etc. Among them, red algae, particularly littamnium carcareum (Red Marine) Algae Lithothamnium calcareum) is preferred.

  In the present invention, as the lime algae, for example, a dried lime algae obtained by drying a lime algae can be used. The dried product of the calcareous algae used in the present invention can be a commercially available product or can be prepared according to a method known in the art.

  In the present invention, the dried lime algae contains 0.1 to 60% by weight, preferably 1 to 60% by weight, more preferably 10 to 60% by weight of calcium. In the present invention, the dried lime algae contains magnesium in an amount of 0.01 to 10% by weight, preferably 0.1 to 10% by weight, and more preferably 1 to 10% by weight. The amounts of calcium and magnesium contained in the calcareous algae can be measured by a known method.

  In the present invention, the lime algae is contained in an amount of 0.01 to 100% by weight, preferably 0.05 to 10% by weight, more preferably 0.1 to 10% by weight based on the total weight of the antiobesity composition. Is done.

  One embodiment of the present invention is an anti-obesity composition containing a globin proteolysate as an active ingredient.

<Globin protein digest>
In the present invention, the globin protein hydrolyzate may be, for example, a hydrolyzate of a globin protein such as hemoglobin or myoglobin, or a globin protein which is contained in a hydrolyzate of a globin protein and separated and purified therefrom. It may be a mixture of peptides or a simple substance. The globin protein hydrolyzate such as hemoglobin or myoglobin contains the globin protein peptide.

  In the present invention, the globin protein peptide is, for example, the tetrapeptide VVYP (Val-Val-Tyr-Pro: SEQ ID NO: 1).

  In the present invention, a globin protein hydrolyzate such as a hydrolyzate of globin protein is, for example, 0.01 to 10% by weight, preferably 0.1 to 10% by weight, more preferably 0.1 to 10% by weight of a tetrapeptide VVYP which is a globin protein peptide. It contains 0.5 to 10% by weight.

  In the present invention, a globin protein hydrolyzate such as a globin protein hydrolyzate is, for example, 0.01 to 100% by weight, preferably 0.05 to 100% by weight, based on the total weight of the antiobesity composition. More preferably, it is contained at 0.1 to 100% by weight.

  When the content of the globin protein hydrolyzate is converted into globin protein peptide (tetrapeptide VVYP), the globin protein peptide (tetrapeptide VVYP) is 0.0001 to 100% by weight based on the total weight of the anti-obesity composition. , Preferably 0.0005 to 100% by weight, more preferably 0.001 to 100% by weight. When the anti-obesity composition of the present invention contains a globin protein peptide (tetrapeptide VVYP) separated and purified from the globin protein hydrolyzate as a globin protein hydrolyzate, the content is shown in this paragraph. Value range.

  The operation related to the hydrolysis of globin protein and the like can be performed according to the method described in International Publication No. WO89 / 06970. The hydrolysis is usually carried out using one or more hydrolases of acidic protease, neutral protease or alkaline protease.

  Specifically, to hydrolyze globin protein, first, a globin protein-containing substance is dispersed in water so as to have a concentration of 5 to 30% by weight (as a solid content), and adjusted to an optimal pH of the protease with an acid or an alkali. Then, a method of adding the protease at once or sequentially and reacting the enzyme at a temperature of 20 to 70 ° C. for 3 to 48 hours can be exemplified.

  One embodiment of the present invention is an anti-obesity composition containing lime algae and a globin protein hydrolyzate as active ingredients. The anti-obesity composition of the present invention, by containing both lime algae and globin protein decomposed product, more significantly reduces the expression level of the lipogenic gene as compared to the case where each of them is contained alone. And / or by significantly increasing the expression level of the fat burning gene, it is extremely useful for preventing and / or improving obesity. The specific description of the lime algae and the globin protein hydrolyzate, the content in the anti-obesity composition, and the like can be applied to the respective descriptions in the above-described embodiment.

  The anti-obesity composition of the present invention can be used as a carrier (eg, a pharmaceutically acceptable carrier, a food or beverage acceptable carrier, or a cosmetic) in addition to the active ingredients such as lime algae and globin protein hydrolyzate. Using an acceptable carrier or the like, the composition can be formulated into an arbitrary dosage form and provided.

<Use of anti-obesity composition>
The anti-obesity composition of the present invention can be used to “prevent obesity”, “ameliorate obesity”, “suppress weight gain”, “suppress body fat accumulation”, and “suppress visceral fat accumulation”. To, increase body energy consumption, promote the breakdown of fat in the body, facilitate fat consumption, promote fat burning, promote metabolism, etc. It is used as a food or drink, a functionally labeled food, a food for specified health use, a nutritionally functional food, a cosmetic, a quasi-drug, or a medicine accompanied by the indication of the function.

  In one embodiment of the present invention, the antiobesity composition of the present invention has an effect of reducing the expression level of a lipogenic gene and is used for reducing the expression level of a lipogenic gene.

  In the present invention, a lipogenesis gene refers to a gene encoding an enzyme or the like involved in promoting fat synthesis in the body or in a cell, or a gene that promotes the expression of an enzyme or the like involved in promoting fat synthesis. Synthetic enzymes (Fatty Acid Synthase: FAS) and the like can be mentioned.

  In one embodiment of the present invention, the antiobesity composition of the present invention has an effect of increasing the expression level of a fat burning gene, and is used for increasing the expression level of a fat burning gene.

  In the present invention, a fat burning gene is a gene encoding an enzyme or the like involved in promoting fat burning, lipolysis, or fat metabolism in the body or in a cell, an enzyme involved in promoting fat burning, lipolysis, or fat metabolism, or the like. Refers to a gene that promotes the expression of carnitine palmitoyltransferase 1A (Carnitine Palmitoyl Transferase 1A: CPT1A).

  The anti-obesity composition of the present invention is, for example, in the case of an oral dose of 0.0001 g to 0.5 g / kg, preferably 0.1 g, in terms of the total amount of lime algae (or globin protein hydrolyzate) when the amount of application per adult is oral. It can be used in such an amount as to be 001 g to 0.3 g / kg, more preferably 0.002 g to 0.1 g / kg.

  When preparing the composition for anti-obesity of the present invention as a food or drink, in addition to lime algae and globin protein hydrolyzate, sweeteners, coloring agents, preservatives, thickeners, stabilizers, gelling agents, sizing agents, Antioxidants, coloring agents, bleaching agents, fungicides (antifungals), yeast foods, gum bases, fragrances, acidulants, seasonings, emulsifiers, pH adjusters, sweet potatoes, swelling agents, nutrient enhancers, other foods and drinks The desired form can be prepared by mixing raw materials and the like. When the composition for anti-obesity of the present invention is made into a food or drink, its form is not particularly limited. For example, supplement-type foods such as gels, granules, fine granules, capsules, tablets, powders, liquids, and semisolids; carbonated drinks, soft drinks, milk drinks, alcoholic drinks, fruit drinks, teas, nutritional drinks, etc. Drinks; powdered drinks, such as powdered juices and powdered soups; gums, tablets, candy, cookies, gummy, rice crackers, biscuits, jelly, and other confectionery; breads, noodles, cereals, jams, seasonings, and the like. These foods are used as foods and drinks for decreasing the expression level of the fat synthesis gene and increasing the expression level of the fat burning gene. In addition to general foods and drinks, it can also be used as a nutraceutical such as a dietary supplement, a functionally labeled food, a food for specified health use, a nutritionally functional food, a food for the sick, and the like.

  When the anti-obesity composition of the present invention is prepared as a pharmaceutical (including quasi-drugs), other medicinal ingredients and pharmaceutically acceptable, if necessary, in addition to lime algae and globin protein hydrolyzate Carriers and additives may be optionally added. Specific examples of the pharmaceutically acceptable carrier and additives include a binder, a disintegrant, a lubricant, a wetting agent, a buffer, a preservative, and a fragrance. When the antiobesity composition of the present invention is prepared as a medicament, its form is not particularly limited. Examples include injections, external preparations, inhalants, suppositories, films, troches, solutions, powders, tablets, granules, capsules, syrups, eye drops, eyewashes, nasal drops and the like. Among these, a form suitable for oral administration (that is, a medicine for internal use) is preferable, and specific examples of such a form include troches, solutions, powders, tablets, granules, capsules, syrups, and drinks. It can be mentioned as a preferred form. These pharmaceuticals (including quasi-drugs) are used as pharmaceuticals having an action of decreasing the expression level of the fat synthesis gene and an action of increasing the expression level of the fat burning gene.

  In order to prepare the anti-obesity composition of the present invention as a cosmetic (including a functional cosmetic) or a quasi-drug for external use, in addition to lime algae and globin protein hydrolyzate, it is pharmaceutically or cosmetically acceptable. Carrier (water, oil component, etc.) may be blended to prepare the desired form. The form of the cosmetic is not particularly limited as long as it can be applied to the skin. For example, liquid, emulsion, powder, solid, suspension, cream, ointment, mousse, granule, tablet, gel, jelly, paste, gel, aerosol, spray, Examples include liniments, packs and the like. These cosmetics are used as cosmetics having an action of decreasing the expression level of the fat synthesis gene and an action of increasing the expression level of the fat burning gene.

  The present invention also includes a kit for decreasing the expression level of a fat synthesis gene and a kit for increasing the expression level of a fat burning gene, comprising the anti-obesity composition of the present invention and instructions for use thereof.

  The instructions for use included in the kit of the present invention indicate that the composition for anti-obesity of the present invention reduces the expression level of a fat synthesis gene and / or increases the expression level of a fat burning gene, thereby obtaining “obesity”. Prevents "," Improves obesity "," Suppresses weight gain "," Suppresses body fat accumulation "," Suppresses visceral fat accumulation "," Increases body energy expenditure " Effective in preventing and / or ameliorating obesity, such as "promoting the breakdown of fat in the body", "facilitating fat consumption", "promoting fat burning", and "promoting metabolism" In addition, it can be described that the active ingredient exhibiting these actions is a calcareous algae or a globin protein degradation product.

  As one embodiment of the present invention, an obesity gene expression regulator (lipogenesis gene expression inhibitor, fat burning gene expression promoter), and a fatty acid synthase activity inhibitor, containing a calcareous algae and / or a globin protein hydrolyzate as an active ingredient And carnitine palmitoyltransferase activity promoter. For specific embodiments of these agents, the description of the antiobesity composition of the present invention can be referred to. Further, one embodiment of the present invention includes a method for treating and / or preventing obesity, which comprises using a calcareous algae and / or a globin protein hydrolyzate. These methods can be said to be methods characterized by using the antiobesity composition of the present invention.

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

<Example 1> Effect of globin protein hydrolyzate and lime algae on lipid metabolism Mouse preadipocyte 3T3-L1 was transformed into a differentiation-inducing medium (0.5 mM Isobutyl-methylxanthine, 1 μM Dexamethasone, 1 μg / mL insulin in 10 (% FBS / DMEM) for 2 days, and then replaced with 10% FBS / DMEM medium for 6 days. After that, cells were cultured for 24 hours in a 10% FBS / DMEM medium containing a test substance. The test was performed as three cases in each group. Cell fat synthesis genes (FAS: Fatty Acid Synthase, fatty acid synthase) and fat burning genes (CPT1A: Carnitine Palmitoyl Transferase 1A, carnitine palmitoyltransferase 1A) were measured by real-time PCR.

  As the globin protein hydrolyzate, an oligopeptide mixture (Val-Val-Tyr-Pro content 0.6% or more, manufactured by MG Pharma Co., Ltd.) having an average chain length of 3 to 5 and composed of porcine erythrocyte hemoglobin protease is 1 mg / g. mL was added. Further, as the lime algae, 1.2 mg / mL of a dry powder (calcium content of 31% or more, magnesium content of 2% or more, manufactured by Marigot Co.) of a red alga, Lithium Almite Lithothamnium calcareum, was added.

  The expression levels of the fat synthesis gene (FAS) and the fat burning gene (CPT1A) were shown as the mean ± standard deviation as relative values to the untreated group. The results are shown in FIGS. Each symbol in FIG. 1 indicates the following. * P <0.05, ** p <0.01 vs. No treatment, #p <0.05, ## p <0.01 vs. Globin proteolysates, ｐp <0.05, ｐp <0.01 vs. Lime algae (multiple comparison test by Ryan method). Each symbol in FIG. 2 indicates the following. * P <0.05, ** p <0.01 vs. No treatment, #p <0.05, ## p <0.01 vs. Globin proteolysates, ｐp <0.05, ｐp <0.01 vs. Lime algae (multiple comparison test by Ryan method).

  It was found that the expression amount of the lipogenesis gene was reduced by the globin proteolysate. In addition, it was found that the expression amount of the fat synthesis gene was decreased and the expression amount of the fat burning gene was increased by the lime algae. Furthermore, the effect was enhanced when a globin protein hydrolyzate was used in combination. From the above results, it was confirmed that the calcareous algae and / or the globin protein hydrolyzate had an anti-obesity effect.

<Example 2> Effect of globin proteolysate and calcareous algae on fat accumulation Mouse preadipocyte 3T3-L1 was transformed into a differentiation-inducing medium (0.5 mM Isobutyl-methylxanthine, 1 μM Dexamethasone, 1 μg / mL Insulin in 10% FBS / (DMEM) for 2 days, and then replaced with 10% FBS / DMEM medium for 6 days. The test substance was added for 8 days from the start of differentiation induction to the end of culture. The test was performed as three cases in each group. Neutral fat in the cells was stained with oil red O and observed under a microscope. The absorbance of oil red O was measured at an absorbance of 492 nm, and a blank value was subtracted to calculate a correction value. Neutral fat content was shown as a mean value ± standard deviation as a relative value to the untreated group. The results are shown in FIG. Each symbol in FIG. 3 indicates the following. * P <0.05, ** p <0.01 vs. No treatment, ## p <0.01 vs. Globin proteolysate 1 mg / mL, Δp <0.01 vs. Lime algae 1.2 mg / mL (multiple comparison test by Ryan method).

  As the globin protein hydrolyzate, an oligopeptide mixture (Val-Val-Tyr-Pro content of 0.6% or more, manufactured by MG Pharma Co., Ltd.) consisting of a protease hydrolyzate of porcine erythrocyte hemoglobin was used. 1 mg / mL was added. As the lime algae, 1.2 mg / mL of a dry powder of red algae littamnium (calcium content of 31% or more, magnesium content of 2% or more, manufactured by Marigot) was added.

  As shown in FIG. 3, it was found that the amount of neutral fat in cells was significantly reduced by the calcareous algae or the globin protein hydrolyzate. Furthermore, the effect was remarkably enhanced by using lime algae and globin protein hydrolyzate in combination. From the above results, it was confirmed that the calcareous algae and / or the globin protein hydrolyzate had an anti-obesity effect.

<Example 3> Effect of globin proteolysate and calcareous algae on body weight The subjects were 12 adult men and women in their 30s to 60s. As a test food, a health food mixed with a globin proteolysate and a calcareous algae was used. Subjects consumed the test food for 30 days. The subject was given a recording sheet, and the body weight was recorded before the start of ingestion of the test food (day 0), on the 10th day of ingestion, and the day after the last ingestion day (31st day).

  As the globin protein hydrolyzate, an oligopeptide mixture (Val-Val-Tyr-Pro content of 0.6% or more, manufactured by MG Pharma Co., Ltd.) consisting of a protease hydrolyzate of porcine erythrocyte hemoglobin was used. They took 500 mg per day. As the lime algae, 600 mg of a dry powder of red algae littamnium (calcium content of 31% or more, magnesium content of 2% or more, manufactured by Marigot) was ingested per day.

  The amount of change in body weight was represented by an average value ± standard error. FIG. 4 shows the results. Each symbol in FIG. 4 indicates the following. * P <0.05, ** p <0.01 vs. Day 0 (Student's t test).

  As shown in FIG. 4, it was confirmed that the ingestion of the health food containing the globin protein hydrolyzate and the calcareous algae significantly reduced the weight of the subject.

  The present invention provides an anti-obesity composition containing a calcareous algae and / or a globin protein hydrolyzate as an active ingredient. The present invention provides a new means for preventing or improving obesity by suppressing weight gain, suppressing body fat accumulation, suppressing visceral fat accumulation, increasing energy consumption in the body, accelerating fat decomposition in the body, and the like. Therefore, it can be used industrially.

Claims (8)

  An anti-obesity composition comprising lime algae and / or a globin proteolysate as an active ingredient.   The anti-obesity composition according to claim 1, wherein the lime algae is a red algae.   The anti-obesity composition according to claim 1 or 2, wherein the lime algae contains 0.1 to 60% by weight of calcium.   The anti-obesity composition according to any one of claims 1 to 3, wherein the lime algae contains 0.01 to 10% by weight of magnesium.   The anti-obesity composition according to any one of claims 1 to 4, wherein the globin protein degradation product contains 0.01 to 10% by weight of the tetrapeptide VVYP.   The anti-obesity composition according to any one of claims 1 to 5, which has an action of reducing the expression level of a fat synthesis gene.   The anti-obesity composition according to any one of claims 1 to 6, which has an action of increasing the expression level of a fat burning gene.   The anti-obesity composition according to any one of claims 1 to 7, which is a food or drink, a functionally labeled food, a food for specified health use, a nutritionally functional food, a cosmetic, a quasi-drug, or a pharmaceutical.

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