JP2011063557A - Ppar activator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a PPAR activator containing a substance having sufficient agonist activity to PPAR and high safety as an active component. <P>SOLUTION: There are provided a PPAR activator containing at least one substance selected from the group consisting of quinua extract, garlic extract, plant worm extract and D-ribose as an active component; and a preventing and/or treatment agent for metabolic syndrome, hyperlipemia or arteriosclerosis containing the PPAR activator. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a PPAR activator.

  Among a group of diseases widely called lifestyle-related diseases, abnormal lipid metabolism, hyperlipidemia associated with them, and abdominal obesity are known as metabolic syndrome. These patients are not only reduced in quality of life, but are at a higher risk of developing fatal vascular disorders such as arteriosclerosis than healthy subjects.

  In contrast to the current situation, there are fibrates such as clofibrate and fenofibrate as drugs that reduce abnormal lipid metabolism. These are known as therapeutic drugs for hyperlipidemia and have an agonistic effect on PPARα among PPAR (peroxisome proliferator-activated receptor) which is a transcription factor. PPARα is involved in the regulation of lipid metabolism and has the effect of reducing blood triglycerides and LDL cholesterol and improving blood HDL cholesterol. Moreover, it has the expression control effect | action of NF-κB (nuclear factor-κB, nuclear factor κB) and AP-1 (activator protein-1) involved in the formation of arteriosclerotic lesions. Therefore, the PPARα activator is useful as a preventive and therapeutic agent for hyperlipidemia and arteriosclerosis. However, fibrate drugs are pharmaceuticals and cannot be used without the permission of a doctor, and there are restrictions when taking them.

  PPARγ, which is a PPAR family other than PPARα, is said to be involved in the regulation of adipocyte differentiation, tissue insulin resistance and immune processes, and PPARβ / δ may be involved in the growth of tumor cells. ing. PPARγ and PPARβ / δ agonists are also expected to be useful as therapeutic agents for lipid metabolism and type 2 diabetes. As exogenous ligands for PPARγ, there are thiazoline-based drugs such as troglitazone and pioglitazone, but these are drugs and cannot be used without the permission of a doctor, and there are restrictions on intake.

  PPARα is selected from the group consisting of fatty acids such as palmitic acid and oleic acid, paprika, horseradish, lemon, chili, sesame, spearmint, and high vegetables as having an agonistic effect on PPAR other than fibrates. At least one or more amphiphilic extracts (Japanese Patent Laid-Open No. 2007-22917: Patent Document 1) have been reported. In PPARγ, capsaicin (Kim CS et al, J Med Food 2004, 7 (3), 267-73: Non-Patent Document 1) has been reported.

  However, these PPAR agonist actions are insufficient compared to existing preparations such as fibrate preparations, and are not practical. For this reason, a material having high safety and a high PPAR activation effect has been desired.

JP 2007-22917 A

Kim CS et al, J Med Food 2004, 7 (3), 267-73.

  An object of the present invention is to provide a PPAR activator comprising a substance having sufficient agonist activity for PPAR and high safety as an active ingredient.

  The inventors of the present invention have made extensive studies to solve the above problems, and screened a large number of organism-derived substances in the process. As a result, it was found that quinoa extract, garlic extract, cordyceps extract, and D-ribose had an excellent PPARα activating action, whereas most substances were not active, and reached the present invention.

That is, the present invention provides the following inventions [1] to [2].
[1] A PPAR activator comprising as an active ingredient at least one selected from the group consisting of quinoa extract, garlic extract, cordyceps extract and D-ribose.
[2] A preventive and / or therapeutic agent for metabolic syndrome, hyperlipidemia or arteriosclerosis comprising the PPAR activator according to [1].

  The PPAR activator of the present invention not only has a sufficient PPAR activating action, but also uses natural ingredients that have been eaten in the past as active ingredients, thus ensuring safety to the living body. Has been. Therefore, the PPAR activator of the present invention is expected to be useful for the treatment and prevention of metabolic syndrome, hyperlipidemia, arteriosclerosis and the like, and can be used as food, medicine and the like.

  The present invention relates to a PPAR activator. PPAR (peroxisome proliferator-activated receptor) is a kind of transcription factor present in the nucleus. The PPAR family includes PPARα, PPARγ, PPARβ / δ, and the like. PPARα is involved in regulation of lipid metabolism, reduction of blood triglycerides and LDL cholesterol, improvement of blood HDL cholesterol, regulation of expression of NF-κB and AP-1.

  A PPAR activator activates PPAR. Activation means to increase the activity, and includes maintaining it when the activity is originally high. When the PPAR activator activates PPARα, the physiological actions of PPARα described above, ie, lipid metabolism, blood triglyceride and LDL cholesterol reduction, blood HDL cholesterol improvement, NF-κB, AP-1 expression regulation, etc. To enhance. Therefore, the PPAR activator of the present invention comprises a lipid metabolism regulator, a blood triglyceride and / or LDL cholesterol reducer, a blood HDL cholesterol improver, an NF-κB and / or AP-1 expression regulator, Also works.

  The activation mechanism of the PPAR activator for PPAR is not particularly limited. For example, the PPAR may be activated by an agonistic action on the PPAR, or the PPAR may be activated by promoting the binding of a ligand to the PPAR, but the former is preferable. It can be confirmed using a commercially available kit that PPAR is activated by an agonistic action on PPAR. Taking PPARα as an example, it can be confirmed using EnBio RCAS for PPARα kit (EnBioTec Laboratories Co., Ltd.) as a kit.

  The PPAR activator of the present invention contains one or more selected from quinoa extract, garlic extract, cordyceps extract, and D-ribose as active ingredients.

  Quinua (Quinoa, scientific name Chenopodium quinoa) is a kind of genus of the genus chenopodium and is a grain native to the Andes region of South America. The quinoa extract means an extract of at least a part of a quinoa plant body, and is preferably an extract of quinoa seeds.

  Garlic (garlic, persimmon, large persimmon, persimmon, scientific name: Allium sativum) is a perennial of the genus Allium. The garlic extract means an extract of at least a part of a garlic plant body, and is preferably an extract of a bulb (bulb).

  Cordyceps sinensis (Berkeley) Saccardo is a fungus and is a kind of Cordyceps ascomycete. Cordyceps extract means an extract of at least a part of the fungus body of cordyceps, and is preferably an extract of cordyceps.

  D-ribose ((3R, 4S, 5R) -5- (hydroxymethyl) tetrahydrofuran-2,3,4-triol) is a kind of monosaccharide (pentose sugar) and constitutes RNA. The origin of D-ribose is not particularly limited, and for example, those extracted from living organisms, commercially available products, and the like can be used.

  The extraction conditions for the quinoa extract, the garlic extract, and the cordyceps extract can be appropriately set so that the PPARα activation action is exhibited.

  Extraction can usually be performed using a solvent. In general, a hydrophilic solvent is used as the solvent. Examples of the hydrophilic solvent include alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol and aqueous solutions thereof, and these are used alone or as a mixed solvent of two or more. obtain. Of these, ethanol is preferred. Ethanol may contain a small amount of other components (for example, other alcohol components), but high purity is preferable. Specifically, the concentration is preferably 90% or more, more preferably 95% or more, and even more preferably 99% or more.

  The amount of the solvent used can be appropriately determined so that the extraction raw material: extraction solvent (mass ratio) is usually 1: 2 to 1:50, preferably 1: 5 to 1:20. The extraction temperature is preferably in the range of 5 to 80 ° C., the extraction time is preferably in the range of 1 hour to 1 week, and the extraction pH is preferably set in the range of 3 to 11, respectively. The extraction can be performed by immersing in a solvent, and may be stirred as necessary. The extraction may be performed twice or more by combining extraction with a certain solvent and extraction with the same solvent or another solvent.

  When extracting the quinoa extract, the garlic extract and the cordyceps extract, filtration and concentration (for example, concentration under reduced pressure) may be performed during or before the extraction as necessary. For example, after extracting parts of quinoa, garlic and cordyceps, the product obtained by filtering to remove the residue and concentrating the supernatant can be used as each extract. In the extraction, dialysis, purification (various chromatography, etc.) and the like may be further performed.

  The subject of the PPAR activator of the present invention is not particularly limited. Useful for humans or non-human vertebrates. In addition, the health status of the target human or non-human vertebrate is not particularly limited, but a significant effect is expected for patients with diseases whose reserves are expected to improve due to PPAR activation and their reserves. The

  The PPAR activator of the present invention may contain a pharmaceutically acceptable carrier in addition to one or more selected from quinoa extract, garlic extract, cordyceps extract, and D-ribose. 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 colorant, a pigment, and a fragrance may be contained as appropriate.

  Examples of the oil component include various fatty acid esters, hydrocarbons, higher fatty acids, higher alcohols and the like. Lubricants include gum arabic, cacao butter, carnauba wax, hydrous silicon dioxide, dry aluminum hydroxide gel, glycerin, magnesium silicate, liquid paraffin, crystalline cellulose, sucrose fatty acid ester, stearyl alcohol, stearic acid, gelatin, lactose Sucrose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, fumaric acid, beeswax sugar and the like. Excipients include gum arabic, ethylcellulose, kaolin, cacao butter, fructose, silicon dioxide, xylitol, citric acid or salts thereof, crystalline cellulose, stearic acid or salts thereof, dextran, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose And polyvinylpyrrolidone, macrogol, calcium hydrogen phosphate, sodium hydrogen phosphate, sucrose, glucose, sorbitol, lactitol, corn starch, potato starch and the like. Examples of the disintegrant include cellulose or a derivative thereof, starch or a derivative thereof. Examples of the binder include hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, gelatin, vinyl pyrrolidone, partially pregelatinized starch and the like. Other specific examples include carotenoid substances (α-carotene, β-carotene, γ-carotene, lycopene, lutein, astaxanthin, zeaxanthin, etc.), coenzyme Q10, vitamin E, tocotrienol, docosahexaenoic acid (DHA), Examples include icosapentaenoic acid (EPA).

  The dosage form of the PPAR activator 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 PPAR activator is not particularly limited, and can be appropriately selected according to the dosage form. For example, when the dosage form is a tablet, one or more active ingredients selected from quinoa extract, garlic extract, cordyceps extract, and D-ribose, and optional ingredients that can be blended as necessary are mixed. Thereafter, there is a method of compression-molding this mixture to obtain a tablet.

  In the PPAR activator of the present invention, the amount of one or more active ingredients selected from quinoa extract, garlic extract, cordyceps extract, and D-ribose is appropriately determined according to the PPAR activation effect. Can be determined. In general, it is preferably 0.005% or more, and more preferably 0.05% or more.

  The dose of the PPAR activator of the present invention varies depending on the age, weight, sex and other conditions, symptoms, disease severity, etc. of the human or non-human vertebrate to be administered, Can be appropriately determined within a range in which the resulting side effects can be tolerated. Usually, it is preferable to administer an amount of 10 mg or more per day as an amount of one or more active ingredients selected from quinoa extract, garlic extract, cordyceps extract, and D-ribose, and 100 to 3000 mg It is more preferred to administer an amount of

  The administration method can be appropriately determined depending on the compounding concentration of the active ingredient, the dosage form, the age, weight, gender and other conditions, symptoms, and disease level of the administration subject. 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 is preferably 12 hours. The relationship between the meal and the administration time may be any of before meal, after meal, and between meals, but is preferably taken within 1 hour after meal. The relationship between exercise and administration time is not limited, but it is preferable to take it within 1 hour after exercise.

  In addition to the administration of the PPAR activator of the present invention, administration of a drug such as a blood circulation promoter, diet therapy, exercise therapy, and the like may be combined. The blood circulation promoter is preferably a plant body of a pepper family, ginger family, solanaceous family, or the like, or an extract thereof, but is not limited thereto. Preferable examples of the plant belonging to the family Pepperaceae, Gingeraceae, and Solanaceae include pepper, hihatsu, hihimodoki, ginger, and chili peppers, but are not limited thereto.

  The PPAR activator of the present invention can be an active ingredient of a therapeutic or prophylactic agent for diseases whose symptoms are improved by PPAR activation. Examples of the disease whose symptoms are improved by PPARα activation include metabolic syndrome, hyperlipidemia, arteriosclerosis and the like. Examples of the disease whose symptoms are improved by PPARγ activation include diabetes, inflammatory disease, arteriosclerosis and the like. Examples of the disease that improves PPARβ / δ activity include cancer.

  The PPAR activator of the present invention is also useful as a medicine, quasi drug, and food. 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.

  In the case of food, it is preferable to display the effect of the present invention. The indication of the effect of the present invention includes an indication that it is used for PPAR activation; an indication that PPAR activation may reduce the risk of a disease whose symptoms are improved, and the like. .

  Here, the PPAR activated food may be used, for example, for a meal for a patient with a disease caused by a decrease in PPAR activity.

  Thus, the food of the present invention activates PPAR when administered to humans or non-human vertebrates and ingested. Therefore, the food of the present invention is useful as a food for prevention and / or treatment of diseases whose symptoms are improved by the activation of PPAR. Moreover, since it can be taken daily if it is food, it is extremely useful as a daily preventive measure for the above diseases.

  Hereinafter, the present invention will be described in detail by way of examples.

Examples 1-4, Comparative Examples 1-9
The PPARα activation effect of quinoa extract (Example 1), garlic extract (Example 2), Cordyceps extract (Example 3), and D-ribose (Example 4) was evaluated.

1. Preparation of Extract Quinua was a seed, garlic was a bulb, and Cordyceps was dried and ground to a powder. 60 g was immersed in 600 mL of 99.5 v / v% ethanol and extracted at room temperature for 5 days. The extract obtained by filtering the residue was concentrated under reduced pressure to obtain 3 g as a quinoa extract, 3.4 g as a garlic extract, and 3.6 g as a cordyceps extract. Also, as Comparative Example 1, spinach leaves, as Comparative Example 2, cargo leaves as lotus leaves, as Comparative Example 3, tea leaves, as Comparative Example 4, buckwheat leaves, as Comparative Example 5, evening primrose as seeds, As Example 6, red rice was prepared with seeds. These were dried and pulverized into powder, 60 g was taken, immersed in 600 mL of 99.5 v / v% ethanol, and extracted at room temperature for 5 days. The extract obtained by filtering the residue was concentrated under reduced pressure, 2.9 g as spinach extract, 3.1 g as leaf extract, 3.4 g as tea extract, 3 g as buckwheat leaf extract, and evening primrose extract As a result, 2.8 g was obtained, and 3 g was obtained as a red rice extract.

2. Preparation of sample In addition to quinoa extract, garlic extract and Cordyceps extract prepared as described above, 10 mg each of D-ribose (Mitsubishi Tanabe Seiyaku) was taken and dissolved in 1 mL of dimethyl sulfoxide. Solution was obtained. In addition to spinach extract, packed leaf extract, tea extract, buckwheat leaf extract, evening primrose extract and red rice extract, sesame peptide (KICSO) as Comparative Example 7 and capsaicin (Japanese) as Comparative Example 8 In the same manner, Kokuyo Pharmaceutical Co., Ltd. was dissolved in 1 mL of dimethyl sulfoxide to obtain a 1% by mass solution.

3. Measurement of PPARα activating action Measurement was performed according to this kit using EnBio RCAS for PPARα kit (EnBioTec Laboratories Co., Ltd.), which measures the activity using a 96-well plate. The sample was added to each well so that the evaluation concentration was 0.05% by mass using the 1% by mass concentration solution prepared as described above.

  In addition, using WY14643 (EnBioTec Laboratories Co., Ltd.) as a positive target, confirming that the kit can measure the activity of PPARα, adding dimethyl sulfoxide (Comparative Example 9) to each well as a negative control, and measuring the absorbance value Then, the PPARα activation effect was evaluated.

  The PPAR activation effect was shown by the ratio of the absorbance value to capsaicin ((sample-negative control) / (capsaicin-negative control)). The results are shown in Table 1.

  As shown in Table 1, the extracts of Comparative Examples 1 to 6 and Sesame Peptide of Comparative Example 7 showed no PPAR activation effect, whereas quinoa extract, garlic extract, Cordyceps extract The product and D-ribose showed a high PPAR activation effect, and in particular, an excellent effect exceeding this was observed even when compared with capsaicin of Comparative Example 8 known as a PPARγ activator.

Claims (2)

  A PPAR activator comprising as an active ingredient at least one selected from the group consisting of quinoa extract, garlic extract, cordyceps extract and D-ribose.   A preventive and / or therapeutic agent for metabolic syndrome, hyperlipidemia or arteriosclerosis comprising the PPAR activator according to claim 1.