Lipid excretion promoter

Abstract

To provide a lipid excretion promoter that promotes the excretion of ingested lipid into stool.SOLUTION: Dai-saiko-to extract has the action of promoting the excretion of ingested lipid into stool and can improve or avoid health problems due to excessive ingestion of lipid even for a person who is essentially predisposed to reduced lipid degradation and metabolism.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for promoting excretion of lipids in feces, which promotes excretion of ingested lipids in feces. [Background technology]

[0002] In recent years, with the Westernization of food culture, the amount of lipid intake by Japanese people has increased, and excessive lipid intake leads to weight gain and is a cause of obesity, etc. Methods aimed at improving the effects of excessive lipid intake include exercise therapy and taking oral medications that enhance lipid decomposition and metabolic ability.

[0003] Daisaikoto is known as an oral medication for obesity. Daisaikoto is prescribed for people with a sturdy build, relatively good physical strength, and a tendency to be constipated, with the aim of improving obesity, the accompanying symptoms of high blood pressure, chronic constipation, etc. (Non-Patent Document 1).

[0004] The mechanism of action of Daisaikoto is thought to be that it activates PPAR gamma, a transcription factor that regulates fat cell differentiation and fat accumulation, by binding to this transcription factor, which may be involved in preventing and reducing visceral fat hypertrophy (Non-Patent Document 2). [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Kampo preparations Kracie Daisaikoto extract granules Kracie Daisaikoto extract tablets Pharmaceutical interview form, revised March 2015 (revised 5th edition) [Non-Patent Document 2] News Release 2014 "Research Results of the Kampo Medicine Daisaikoto," October 2014, Kobayashi Pharmaceutical Co., Ltd., [Retrieved May 18, 2020], Internet<URL: https: / / www.kobayashi.co.jp / corporate / news / 2014 / 141031_02 / index.html> Summary of the Invention [Problem to be solved by the invention]

[0006] The adverse effects of excessive lipid intake can be improved to some extent by increasing the body's lipid decomposition and metabolic capacity, but there is a limit to how much lipid decomposition and metabolic capacity can be improved by taking medication. In particular, people who have been obese for more than five years (for example, men with a body fat percentage of 25% or more and a waist size of 85 cm or more, and women with a body fat percentage of 25% or more and a waist size of 90 cm or more (especially women who have been obese since menopause due to a decrease in the amount of female hormones related to lipid metabolism)) have a constitution that is essentially reduced in lipid decomposition and metabolic capacity, and it is considered difficult to improve lipid decomposition and metabolic capacity in such people.

[0007] Therefore, excreting lipids together with stool and increasing the amount of lipid excreted will help improve or avoid health problems caused by excessive lipid intake, and is thought to be particularly effective in avoiding the adverse effects of lipid intake for people with a constitution that is inherently impaired in their lipid decomposition and metabolic ability.

[0008] However, there have been no reports that have actually verified that Daisaikoto has the effect of promoting the excretion of ingested lipids into feces. Also, people with constitutions that have an inherently reduced lipid decomposition and metabolic ability are not expected to benefit from improved lipid decomposition and metabolic ability, and so they do not usually take Daisaikoto.

[0009] An object of the present invention is to provide an agent for promoting excretion of lipids in feces, which promotes excretion of ingested lipids in feces. [Means for solving the problem]

[0010] The present inventors have conducted extensive research to solve the above problems and have found that Daisaikoto extract has the effect of promoting the excretion of ingested lipids into feces, and that this makes it possible to improve or avoid the effects of excessive lipid intake even in people with constitutions that are essentially impaired in lipid decomposition and metabolism.The present invention was completed based on this knowledge and through further research.

[0011] That is, the present invention provides the following aspects. Item 1. A stool lipid excretion promoter containing Daisaikoto extract. Item 2. The fecal lipid excretion promoter according to Item 1, which is applied to people who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more. Item 3. The fecal lipid excretion promoter according to Item 1 or 2, which is applied to people who are not constipated. Effect of the Invention

[0012] According to the present invention, it is possible to promote the excretion of ingested lipids in feces, and it is possible to improve or avoid the effects of excessive lipid intake even in people with a constitution that is inherently impaired in the ability to break down and metabolize lipids. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The fecal lipid excretion promoter of the present invention is characterized by containing Daisaikoto extract. The fecal lipid excretion promoter of the present invention will be described in detail below.

[0014] Daisaikoto extract As a Kampo prescription for Daisaikoto, the Kampo prescription described in "New Guide to General Kampo Prescriptions" (supervised by Yukihiro Goda and Takashi Hakamzuka, edited by the Japan Kampo Herbal Medicine Preparation Association, published by Jiho Co., Ltd.) is preferable, and specifically, a mixture of herbs consisting of Bupleurum Root, Pinellia Root, Scutellaria Root, Pheasant's Eye, Peony Root, Shokyo Root, Taisou Root, and Daio Root can be mentioned. In addition, Daisaikoto includes the mixture of herbs (Kampo prescriptions) described in currently used Kampo-related letters, as stipulated in the "Basic Handling Policy for Kampo Preparations" established by the Kampo Herbal Medicine Investigation Committee.

[0015] The amounts of each herb that makes up Daisaikoto include 3 to 12 parts by weight, preferably 4 to 9 parts by weight, of Bupleurum Root; 2 to 8 parts by weight, preferably 2.5 to 6 parts by weight, of Pinellia Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Scutellaria Root; 1 to 4 parts by weight, preferably 1.5 to 3 parts by weight, of Pheasant's Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Peony Root; 0.5 to 2 parts by weight, preferably 1 to 1.5 parts by weight, of Zingiber Root; 1.5 to 6 parts by weight, preferably 2 to 4.5 parts by weight, of Taiso Root; and 0.5 to 2 parts by weight, preferably 1 to 1.5 parts by weight.

[0016] Suitable examples of herbal medicine preparations used in the production of the Daisaikoto extract used in the present invention include 6 parts by weight of Bupleurum Root, 4 parts by weight of Pinellia Root, 3 parts by weight of Scutellaria Root, 2 parts by weight of Pheasant's Root, 3 parts by weight of Peony Root, 1 part by weight of Zingiber Root, 3 parts by weight of Atractylodes Root, and 1 part by weight of Daio.

[0017] The extract form of Daisaikoto may be either a liquid extract such as a soft extract, or a solid dry extract powder.

[0018] The liquid extract of Daisaikoto can be obtained by subjecting a mixture of herbal medicines according to the Daisaikoto prescription to an extraction process and concentrating the resulting extract as necessary. The dried extract powder of Daisaikoto can be obtained by drying the liquid extract.

[0019] In the production of Daisaikoto extract, the extraction solvent used in the extraction process is not particularly limited, but suitable examples include water or aqueous ethanol. The extraction process of Daisaikoto is not particularly limited, but for example, the total weight (converted to dry weight) of the herbal medicine contained in Daisaikoto is extracted with about 20 times the amount of extraction solvent, then concentrated to 1 / 2 volume, and solids are removed to obtain a liquid extract of Daisaikoto. In addition, this liquid extract is subjected to drying process to obtain a dried extract powder of Daisaikoto. The drying process is not particularly limited, and any known method can be used, for example, spray drying method, or a method of adding a suitable adsorbent (e.g., silicic anhydride, starch, etc.) to a soft extract with a high extract concentration to obtain an adsorbed powder, etc.

[0020] In the present invention, when using an extract as Daisaikoto, the extract prepared by the above-mentioned method may be used, or a commercially available one may be used. For example, as the dried extract powder of Daisaikoto, Daisaikoto Dried Extract AM, Daisaikoto Dried Extract SN, and Daisaikoto Dried Extract Powder (all manufactured by Nippon Powder Co., Ltd.), Daisaikoto Dried Extract F, and Daisaikoto Dried Extract-F (all manufactured by Alps Pharmaceutical Co., Ltd.) are known as commercial products and can be obtained commercially.

[0021] In the fecal lipid excretion promoter of the present invention, the content of Daisaikoto extract is not particularly limited as long as the effect of the present invention is exhibited, but is usually 5-100% by weight, preferably 10-90% by weight, more preferably 20-80% by weight, and even more preferably 30-60% by weight, calculated as the amount of dried extract powder of Daisaikoto extract. In the present invention, the amount of dried extract powder of Daisaikoto refers to the amount of dried extract powder itself when using dried extract powder of Daisaikoto, and refers to the amount calculated as the amount remaining after removing the solvent when using liquid extract of Daisaikoto. In addition, when the dried extract powder of Daisaikoto contains additives such as adsorbents added during production, the amount refers to the amount excluding the additives.

[0022] Other Ingredients The fecal lipid excretion promoter of the present invention may be composed of Daisaikoto extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavorings, fragrances, powders, thickeners, dyes, and chelating agents. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the type of additives and bases used, the formulation form of the fecal lipid excretion promoter, etc.

[0023] In addition, the fecal lipid excretion promoter of the present invention may contain other nutritional components or pharmacological components as necessary, in addition to the Daisaikoto extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set according to the type of components used and the formulation form of the fecal lipid excretion promoter.

[0024] Formulation The formulation of the fecal lipid excretion promoter of the present invention is not particularly limited as long as it can be administered orally, and examples thereof include solid formulations such as powders, fine granules, granules (including dry syrup), tablets, pills, capsules (soft capsules, hard capsules), etc.; semi-solid formulations such as jellies; and liquid formulations such as liquids, suspensions, syrups, etc. Among these formulations, solid formulations are preferred from the viewpoints of the stability and portability of the contained ingredients.

[0025] To prepare the fecal lipid excretion promoter of the present invention in the above-mentioned formulation form, Daisaikoto extract, and additives, bases, and pharmacological ingredients added as necessary may be used to formulate the agent in accordance with conventional formulation methods used in the pharmaceutical field.

[0026] Purpose The fecal lipid excretion promoter of the present invention is used to promote the excretion of ingested lipids into feces. In this way, it is possible to promote the excretion of lipids into feces, and thus to improve or avoid health problems (weight gain, visceral fat gain, etc.) caused by excessive lipid intake.

[0027] Furthermore, it has been recognized that for people with constitutions that inherently have reduced lipid decomposition and metabolic capabilities, improvement in lipid decomposition and metabolic capabilities cannot be expected even if they take obesity improvement agents, and so there has been no custom of taking Daisaikoto. However, the fecal lipid excretion promoter of the present invention promotes the excretion of lipids in the stool, making it possible to suppress the adverse effects of lipid intake even for people with constitutions that inherently have reduced lipid decomposition and metabolic capabilities.

[0028] Considering the effect of the present invention, the fecal lipid excretion promoter of the present invention is suitable for application to people with a constitution that is essentially reduced in lipid decomposition and metabolism, which was not applicable to Daisaikoto before. Such people include people who have been obese for more than 5 years, and the obese state includes a body fat percentage of 25% or more and a waist size of 85 cm or more for men and 90 cm or more for women. Among these, preferably, women who have been obese for more than 5 years with a body fat percentage of 25% or more and a waist size of 90 cm or more are included, and more preferably, women who have been obese for more than 5 years with a body fat percentage of 25% or more and a waist size of 90 cm or more, and whose obese state has been continued due to the reduction in the amount of female hormones related to lipid metabolism after menopause are included.

[0029] Specific examples of people with a constitution that is inherently impaired in lipid decomposition and metabolic ability include people with adipose tissue whose lipid decomposition capacity, as measured in the lipid decomposition capacity evaluation test described below, is 5mEq / g or less, preferably 3mEq / g or less, more preferably 1mEq / g or less, even more preferably 0.5mEq / g or less, and particularly preferably 0.3mEq / g or less. <Fat decomposition ability evaluation test> First, adipose tissue is collected from the subcutaneous tissue of a subject. The obtained adipose tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg / mL noradrenaline and 2% by weight bovine serum albumin (BSA) is added to 0.2 g of the washed adipose tissue, and incubated at 37°C for 2 hours. The supernatant is then collected, and the amount of free fatty acids released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acids released per 1 g of adipose tissue (mEq / g) is calculated as the lipolysis power.

[0030] It is known that adipose tissue is activated by noradrenaline stimulation, and the accumulated fat is broken down to release free fatty acids. In the lipolysis ability evaluation test, the decomposition ability of adipose tissue is evaluated by measuring the amount of this free fatty acid released.

[0031] Furthermore, Daisaikoto has been used for people who tend to be constipated, but people who are not constipated generally have active peristaltic movements in not only the large intestine but also the small intestine, so that fat absorption is further suppressed and more excess lipids can be excreted in the stool. From this perspective, people who are not constipated are also suitable subjects for the fecal lipid excretion promoter of the present invention. Not being constipated means having a bowel movement at least once a day.

[0032] Dosage / Usage The fecal lipid excretion promoter of the present invention is used by oral administration. The dosage of the fecal lipid excretion promoter of the present invention is appropriately set according to the age, sex, constitution, etc. of the subject of administration, but for example, it is sufficient to take about 1 to 10 g, preferably about 1.3 to 6 g, more preferably about 1.5 to 4 g, and even more preferably about 1.8 to 2.5 g of dried extract powder per person per day, 1 to 3 times a day, preferably 2 or 3 times a day. The timing of taking is not particularly limited, and may be before, after, or between meals, but is preferably before (30 minutes before a meal) or between meals (2 hours after a meal).

[0033] Furthermore, since the effect of promoting excretion of lipids into the stool by the fecal lipid excretion promoter of the present invention is achieved by continuous administration, it is preferable to take the fecal lipid excretion promoter of the present invention continuously (specifically, for 3 weeks or more, preferably 6 weeks or more, and more preferably 8 weeks or more). EXAMPLES

[0034] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0035] Manufacturing of Daisaikoto extract powder The raw herbs were used in the ratio of 6.0 (parts by weight, the same below), 4.0 (parts by weight), 1.0 (parts by weight), 3.0 (parts by weight), 3.0 (parts by weight), 3.0 (parts by weight) of Peony Root, 3.0 (parts by weight), 3.0 (parts by weight) of Chinese Peony Root, 3.0 (parts by weight), 2.0 (parts by weight), and 1.0 (parts by weight) of Rhizome. After chopping, they were extracted with 20 times the weight of water (460 parts by weight) at about 100°C for 1 hour, centrifuged to obtain an extract, which was concentrated under reduced pressure and dried using a spray dryer to obtain Daisaikoto extract powder. The obtained Daisaikoto extract powder was 2.4g per 13.8g of raw herb mixture. The drying using the spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0036] Test Example 1: Evaluation of the effect of promoting excretion of lipids into feces and the effect of reducing body weight Mice (ddY mice, 10 weeks old, female) were fed a high-fat diet (HFD32, CLEA Japan, Inc.) ad libitum for 3 weeks to create obese model mice. After measuring the body weight of these obese model mice, they were divided into two groups, a control group (control example) and a Daisaikoto group (six mice in each group, two mice in each cage). In the Daisaikoto group, the obese model mice were fed a diet containing 4% Daisaikoto extract by weight in the high-fat diet for 56 days. In the control group, the mice were fed a high-fat diet without Daisaikoto extract for 56 days. Feces were collected on the 51st to 56th days after the start of the experiment and freeze-dried.

[0037] Lipids were extracted from the freeze-dried feces with a low polarity solvent, and the total lipid content in the feces was measured by gravimetric analysis. Specifically, after crushing the freeze-dried feces, 100 mg was weighed out and extracted twice with 500 μL of a chloroform / ethanol solution (chloroform:ethanol (volume ratio) = 2:1). The extract was vacuum dried at 40°C, and the weight of the resulting extract (lipid) was measured and divided by the number of mice in each group to calculate the average total lipid excretion per mouse. As a result, the average total lipid excretion per mouse in the control group was 93.9 mg / mouse, and the average total lipid excretion per mouse in the Daisaikoto group was 134.2 mg / mouse, and a significant and remarkable lipid excretion promoting effect was observed in the Daisaikoto group.

[0038] In addition, the weight of the obese model mice in each group was measured at the start of breeding (day 0) and on the final day of breeding (day 56). The weight of each group at the start of breeding was set as 100%, and the percentage of the weight on the final day of breeding was calculated as the weight change rate (%). This was then divided by the number of mice in each group to calculate the average weight change rate per mouse. As a result, the average weight change rate per mouse in the control group was 129.4% / mouse, and the average weight change rate per mouse in the Daisaikoto group was 115.2% / mouse, indicating a significant weight gain suppression effect in the Daisaikoto group.

[0039] During the breeding period, no diarrhea was observed in any of the mice. The daily fecal mass of each mouse was 304-397 mg / day / mouse in dry weight, with no significant difference between groups.

[0040] From the above results, it was confirmed that administration of Daisaikoto extract promotes the excretion of lipids into feces. It was also confirmed that administration of Daisaikoto extract suppresses weight gain, and it is believed that one of the reasons for the suppression of weight gain by Daisaikoto extract is the effect of promoting the excretion of lipids into feces.

[0041] Reference test example: Evaluation of weight reduction effects by age group The weight-reducing effect of Daisaikoto extract on people with a constitution that has essentially decreased lipid decomposition and metabolic ability was evaluated. Specifically, 12 women (Women A to L; selected so that the difference in average weight was within 5 kg) who have had a body fat percentage of 25% or more and a waist size of 90 cm or more since menopause for more than 5 years were used as monitors, and they were given 2 g of Daisaikoto extract powder three times a day for 12 weeks, and their weight change compared to before the start of the treatment was measured. Of these, Women A to F have had a body fat percentage of 25% or more and a waist size of 90 cm or more since menopause for more than 5 years. In addition, all except Women C, D, and G were aware of constipation.

[0042] The results are shown in Table 1. The subjects were found to have a constitution in which the decomposition and metabolism of lipids were essentially decreased, but when they were administered Daisaikoto extract, weight loss was observed. Women who have had a body fat percentage of 25% or more and a waist size of 90 cm or more for more than 5 years have essentially decreased decomposition and metabolism of lipids, and it was previously thought that Daisaikoto extract would not be effective. However, as shown in the above Test Example 1, Daisaikoto extract has an effect of promoting lipid excretion in the stool, and this effect is considered to be one of the factors that contributed to the weight loss effect even in obese subjects with essentially decreased decomposition and metabolism of lipids. Furthermore, the weight loss was particularly large for women C, D, and G who did not have constipation symptoms. This is considered to be due to the fact that people who are not constipated generally have active peristalsis in the small intestine, which further suppresses fat absorption.

[0043] [Table 1]

Claims

1. A stool lipid excretion promoter containing Daisaikoto extract.

2. The fecal lipid excretion promoter according to claim 1, which is applied to a person who has had a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more.

3. The agent for promoting lipid excretion in feces according to claim 1 or 2, which is applied to people who are not constipated.

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