JP2016069366A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition which is excellent in the inhibition or improvement of obesity, particularly the inhibitory effect on weight gain and/or on accumulation of body fat, compared with the conventional Bofu-tsusho-san.SOLUTION: The invention provides a pharmaceutical composition containing other crude drug ingredients excluding at least one crude drug ingredient selected from the group consisting of Saposhnikovia divaricata, Cnidium officinale Makino, Brasilicactus haselbergii, talc, and Angelica acutiloba among the crude drug ingredients constituting Bofu-tsusho-san (Glycyrrhiza, Rheum rhabarbarum, Gardenia jasminoides, Ephedra, Natrium sulfuricum, Forsythia suspensa, Zingiber officinale Roscoe, Scutellaria baicalensis, a Nepeta japonica, Platycodon grandiflorus, Mentha arvensis var. piperascens, Paeonia lactiflora, Atractylodes japonica Koidz, Cnidium officinale Makino, Brasilicactus haselbergii, Saposhnikovia divaricata, Angelica acutiloba, and talc), or containing all of the above crude drug ingredients, in which the compounding amount of talc is less than 100 ppm in terms of the aluminium content derived from talc per 100% by weight of the pharmaceutical composition.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical composition excellent in suppressing or improving obesity, in particular, suppressing body weight gain and / or suppressing body fat accumulation, as compared with conventional windproof sansho. Furthermore, the present invention, in addition to the above-mentioned effects, has an effect of suppressing an increase in blood glucose level, an effect of suppressing an increase in blood insulin concentration, an effect of suppressing an increase in liver triglyceride level, and / or an increase in total liver cholesterol, The present invention relates to a pharmaceutical composition excellent in inhibitory action.

  It is said that excessive fat accumulation may cause lifestyle-related diseases such as diabetes, hyperlipidemia, arteriosclerosis, etc., especially in the case of visceral fat type obesity Has been pointed out. In recent years, interest in lifestyle-related diseases and obesity has increased further, and there has been a demand for the development of pharmaceuticals effective for the prevention, improvement and / or treatment of obesity, particularly visceral fat obesity.

  Currently used as anti-obesity-related medicines include Chinese herbal medicines such as Fufutsu Seisaku, and in recent years, it has been particularly confirmed that they are effective in reducing visceral fat (eg, non-patent literature). 1). However, because of the side effect of hepatic disorder (see Non-Patent Document 2, for example), there is a problem in increasing the dose to obtain the visceral fat reduction effect. If the amount is too small, the visceral fat reduction effect cannot be obtained.

  Under such circumstances, there has been a demand for the development of a drug effective for the prevention, improvement and / or treatment of obesity, particularly visceral fat type obesity, without increasing the dose to such an extent that side effects occur.

Fiscal 2002 Science and Technology Research Fund Regional Leading Research Research Results Report TSUMURA Futsutsu Seisaku Extract Granule (for medical use) package insert

  The present invention relates to a pharmaceutical composition having an excellent inhibitory action on body weight gain and / or body fat accumulation, in particular, a pharmaceutical composition having the above-described inhibitory action superior to that of conventionally known Fukatsu-san The purpose is to provide. Further, in addition to the above-mentioned action, the present invention has an excellent inhibitory action for increasing blood glucose level, increasing blood insulin concentration, increasing liver triglyceride level, and / or increasing total liver cholesterol, compared with the conventional windbreaking sansho. It aims at providing the pharmaceutical composition which has.

  As a result of diligent investigations to solve the above-mentioned problems, the present inventors have found that there is a taste-removing agent in which any one of Bow Fu, Senkyu, Gypsum, Kasseki, and Toki is removed from the components of Fufutsu Seisaku. As a result, it has been found that compared with the conventionally known Fukatsu Seisaku, it is superior in suppressing or improving obesity, particularly in suppressing or reducing weight gain and / or suppressing or reducing visceral fat accumulation. Furthermore, from this finding, if the content of Bow Fu, Senkyu, Gypsum, Toki, and / or Casseki during the windbreaking sansho is reduced, the above effect increases with the decrease in the content, that is, these herbal medicines. It was speculated that the component has an action to suppress the above effect in a dose-dependent manner. In addition to the above-mentioned effects, the present inventors have also found that the above-mentioned flavour-removing agent has a blood glucose level increase inhibitory effect, a blood insulin concentration increase suppressive effect, and a liver triglyceride amount, as compared with the conventional Fengtsu Seisaku. It was confirmed that the effect of suppressing the increase and / or the effect of suppressing the increase of the total amount of liver cholesterol was excellent. The present invention has been completed as a result of further research based on these findings.

The present invention provides the following pharmaceutical composition and method for producing the same.
(I) Pharmaceutical composition I-1. Of the herbal medicines that make up Fengshui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peonies, peony, senkyu, gypsum, boufu, touki, and caseki) Including at least one herbal ingredient other than at least one herbal ingredient selected from the group consisting of cucumber, cucumber, gypsum, gypsum, gusset, and toki, It is characterized by being less than 100 ppm, preferably not more than 30 ppm, more preferably not more than 20 ppm, still more preferably not more than 15 ppm, particularly preferably not more than 11 ppm in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition. Pharmaceutical composition.

  I-2. Of the herbal medicines that make up Fengshui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peonies, peony, senkyu, gypsum, boufu, touki, and caseki) Including the above-mentioned herbal ingredients other than at least one herbal ingredient selected from the group consisting of cucumber, cucumber, senkyu, gypsum, and toki, and the amount of casseki derived from Kasseki per 100% by weight of the pharmaceutical composition A pharmaceutical composition characterized in that it is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the aluminum content.

  I-3. Of the herbal ingredients that make up Fufutsu Seisaku, any other of the herbal ingredients other than Bowfu, Kasseki and Toki are included, or the herbal ingredients are included, and the amount of Kasseki is the pharmaceutical composition. A pharmaceutical composition characterized in that it is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less, in terms of the aluminum content derived from Kasseki per 100% by weight of the product. .

  I-4. A medicinal composition characterized by not containing any one of nematode or gypsum among herbal medicine constituents constituting Fukatsutsu Seisaku.

  I-5. Of the herbal ingredients that make up Fufutsu Seisaku, the other herbal ingredients except for any one of Senkyu, Gypsum, Kaseki and Toki are included, or the herbal ingredients are included, and the amount of Kaseki is A pharmaceutical composition characterized in that it is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, and particularly preferably 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition. Composition.

  I-6. Of the herbal medicine components that make up Fukatsutsu Seisaku, the other herbal medicine components other than any one of Senkyu, Gypsum, and Kasseki are included, or the above herbal medicine ingredients are included, and the amount of Kasseki is Pharmaceutical composition characterized in that it is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, even more preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the composition. object.

  I-7. Alkaline-derived aluminum containing 100% by weight of the pharmaceutical composition containing 100% by weight of the herbal medicinal component other than Kasseki, or including the herbal medicinal component, and the blended amount of Kasseki A pharmaceutical composition characterized by being less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of content.

(II) Method for producing pharmaceutical composition
II-1. Of the herbal medicines that make up Fengshui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peonies, peony, senkyu, gypsum, boufu, touki, and caseki) Including at least one herbal ingredient other than at least one herbal ingredient selected from the group consisting of cucumber, cucumber, gypsum, gypsum, gusset, and toki, In addition, the herbal medicine described above so that it becomes less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition. Extraction of ingredients Comprising the step of preparing a process for preparing a pharmaceutical composition I-1, wherein.

  II-2. Of the herbal medicines that make up Fengshui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peonies, peony, senkyu, gypsum, boufu, touki, and caseki) Including the above-mentioned herbal ingredients other than at least one herbal ingredient selected from the group consisting of cucumber, cucumber, senkyu, gypsum, and toki, and the amount of casseki derived from Kasseki per 100% by weight of the pharmaceutical composition Including the step of preparing an extract of the above herbal medicine component so that it is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the aluminum content of Pharmaceutical composition described in I-2 The method of production.

  II-3. Of the herbal ingredients that make up Fufutsu Seisaku, any other of the herbal ingredients other than Bowfu, Kasseki and Toki are included, or the herbal ingredients are included, and the amount of Kasseki is the pharmaceutical composition. Extract of herbal medicine component so that it becomes less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the product. A method for producing a pharmaceutical composition according to I-3, which comprises the step of:

  II-4. The method according to I-4, comprising a step of preparing an extract of herbal medicine components so as to include the other herbal medicine components excluding either nematode or gypsum among herbal medicine constituents constituting Fengtsu Sanseiki A method for producing a pharmaceutical composition.

  II-5. Of the herbal ingredients that make up Fufutsu Seisaku, the other herbal ingredients except for any one of Senkyu, Gypsum, Kaseki and Toki are included, or the herbal ingredients are included, and the amount of Kaseki is It is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, even more preferably 15 ppm or less, particularly preferably 11 ppm or less in terms of the content of aluminum derived from Kasseki per 100% by weight of the pharmaceutical composition. The manufacturing method of the pharmaceutical composition of I-5 including the process of preparing an extract.

  II-6. Of the herbal medicine components that make up Fukatsutsu Seisaku, the other herbal medicine components other than any one of Senkyu, Gypsum, and Kasseki are included, or the above herbal medicine ingredients are included, and the amount of Kasseki is Extraction of crude drug components so that it is less than 100 ppm, preferably not more than 30 ppm, more preferably not more than 20 ppm, still more preferably not more than 15 ppm, particularly preferably not more than 11 ppm in terms of the aluminum content derived from Kasseki per 100% by weight of the composition. The manufacturing method of the pharmaceutical composition of I-6 including the process of preparing an extract.

  II-7. Alkaline-derived aluminum containing 100% by weight of the pharmaceutical composition containing 100% by weight of the herbal medicinal component other than Kasseki, or including the herbal medicinal component, and the blended amount of Kasseki Including a step of preparing an extract of herbal ingredients so that the content is less than 100 ppm, preferably 30 ppm or less, more preferably 20 ppm or less, further preferably 15 ppm or less, and particularly preferably 11 ppm or less. A method for producing the pharmaceutical composition described.

  The pharmaceutical composition of the present invention is more effective in suppressing obesity or improving obesity than conventional windbreaking sansue. More specifically, the pharmaceutical composition of the present invention has an excellent effect of suppressing or reducing weight gain and / or suppressing or reducing body fat accumulation, as compared with conventional windbreaking sansho. In the present specification, “internal fat” mainly means visceral fat. As described above, the pharmaceutical composition of the present invention is effective in preventing, improving and / or treating obesity because it is excellent in suppressing or reducing body weight gain and / or suppressing or reducing body fat accumulation.

  In addition to the above effects, the pharmaceutical composition of the present invention has a blood glucose level increase inhibitory effect, a blood insulin concentration increase suppressive effect, a liver triglyceride level increase suppressive effect, and / or a liver, as compared with the conventional windbreaking sansho. It has the effect of being excellent in the total cholesterol content increase inhibitory action.

  In recent years, it has been pointed out that the incidence of myocardial infarction, cerebral infarction, etc. is increased by suffering from metabolic syndrome combined with two or more of hyperglycemia, hypertension and hyperlipidemia in addition to visceral fat type obesity. ing. The pharmaceutical composition of the present invention is useful as a pharmaceutical composition for preventing, improving and / or treating metabolic syndrome by exerting the above-described effects.

Each obese model mouse at 4 weeks after sample administration (control group (control example), Fengtsu Seiki administration group (comparative example), Bow-fu-no-fufu-tsu-san treatment group (Example 1), Senkyu-free Fudotsu Seiki-san) Administration group (Example 2), gypsum-free Fengtsu-san-san administration group (Example 3), Kasseki-exclusive Feng-tsu-san-san administration group (Example 4), and touki-free Fengtsu-san-san administration group (Example 5) : Also shows the fat weight (g) around the internal organs (retroperitoneum, testis, intestine, kidney) of FIGS. 2 to 5 (Experimental Example 2). The bar graph in FIG. 1 shows the fat weights (g) around the peritoneum, around the testis, between the intestines, and around the kidney, and their respective weights in order from the left side for each of the sample administration groups shown on the horizontal axis. The total amount (g) is shown. The liver triglyceride amount (mg / g) of each obese model mouse 4 weeks after administration of the sample is shown (Experimental Example 2). The total amount of liver cholesterol (mg / g) of each obese model mouse 4 weeks after sample administration is shown (Experimental Example 2). The blood glucose level (mg / dl) of each obese model mouse 4 weeks after administration of the sample is shown (Experimental Example 2). The blood insulin concentration (ng / ml) of each obese model mouse 4 weeks after sample administration is shown (Experimental Example 2). Kaseki-extracted windproof sansho-san extract (Example 4: aluminum content 0 ppm), and Kazeki-san-san extract with reduced cassetaki content (Example 6: aluminum content 1 ppm, Example 8: aluminum content 11 ppm), and conventional windproof The result of having evaluated the reduction | decrease effect of the accumulation | storage fat in an adipocyte using each tsushosan extract (comparative example: aluminum content 100ppm) is shown. In addition, a result shows the fat reduction rate by the conventional wind-proof Tsushosan extract (comparative example: aluminum content 100ppm) as 100%.

  The medicinal composition to which the present invention is directed includes herbal medicine components that make up Fengtsu Sansho (licanthus, daisou, sanshishi, mao, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peony, peanut, senkyu Pharmaceutical composition containing at least one herbal ingredient selected from the group consisting of Bowfu, Senkyu, Gypsum, Kasseki, and Toki, and other herbal ingredients And a pharmaceutical composition in which the amount of Kasseki is less than 100 ppm in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition.

(1) Specific examples of plant materials of conventionally known Feng Shui San Feng Shuangsan are, for example, Maou (Ephedra sinica Stapf, Ephedra intermedia Schrenk et CA Meyer, Ephedra equisetina Bunge), Licorice (Glycyrrhiza uralensis Fischer, Glycyrrhiza glabra Linne, Zingiber officinale Roscoe, Schizonepeta tenuifolia Briquet, Forsythia suspense Vahl, Forsythia viridissima Lindley, Angelica acutiloba Kitagawa, Angelica acutiloba Kite var. Pallas, Cendium officinale Makino, Sanshishi (Gardenia jasminoides Ellis), Mentha (Mentha arvensis Linne var. coreanum Nakai or their hybrids) (Atractylodes japonica Koidzumi ex Kitamura, Atractylodes ovata De Candolle), Pepper (Platycodon grandiflorum A. De Candolle), Plum (Scutellariae baicalensis Georgi), Pepper (sodium sulfate: sodium sulfate), Kasseki (talc: natural hydrous aluminum silicate Inclusions) and gypsum (gypsum: hydrous calcium sulfate). These plant materials have specified use sites according to the Japanese Pharmacopoeia.

  In general, Fufutsu Seisaku can be prepared according to, for example, “General Kampo Prescription Guide” (supervised by the Ministry of Health and Welfare Pharmaceutical Affairs Bureau, edited by the National Pharmacopoeia Specialist Committee, published by Yakuho Hokpo). According to “Guide for general-purpose Kampo prescription”, its components and amounts are as follows: Toki 1.2 (parts by weight, the same applies hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, Pepper 1.2, Pepper 1.2, Kei-Gai 1.2, Bow-Fu 1.2, Mao-1.2, Daio-1.5, Bow-Sho 1.5, Sandalwood 2.0, Pepper 2.0, Ogon 2.0 Licorice 2.0, gypsum 2-3, casserole 3-5, and in principle, this is extracted with hot water of 20 times its weight (thus 560-620 parts by weight) and then reduced to 1/2 volume. It can be used until it concentrates until it becomes and remove | excludes solid content (extract).

  Depending on the letter, the above ingredients may not contain peanuts (for example, “Experimental Kampo Prescription Volume Collection”, Takatsuka Otsuka / Michiaki Yahaji, published by Nippon Shokudo Co., Ltd.) "Sequential Chinese medicine is this," edited by Osaka Yomiuri Shimbun, published by Naniwasha), and in the above quantities, 1.2 (parts by weight) are all set to 1.5 (parts by weight) (for example, "Myung Chinese medicine prescription", Kazuo Nishioka , Published by Nantaro Co., published by Nantaro Takahashi, etc.). In addition, as a method of making Windproof Tsushosan extract, it is said that 400 parts by weight of water is added to each of the above components other than bow show, decocted to 200 parts by weight, debris is removed, and then bow show is added (for example, “Wakan Medicine Handbook” Some of them are made slightly differently from the above, such as Michinori Kubo, Kenzo Moriyama, published by Yoikusha).

(2) Pharmaceutical composition of the present invention The pharmaceutical composition of the present invention, as described above, is selected from the group consisting of Bow Fu, Senkyu, Gypsum, Kasseki, and Toki among the above herbal ingredients of Fufutsu Seisaku. A pharmaceutical composition containing at least one herbal ingredient other than the above, and the other herbal ingredients as well as all of the herbal ingredients, wherein the amount of casseki is an aluminum derived from casseki per 100% by weight of the pharmaceutical composition. A pharmaceutical composition that is less than 100 ppm in terms of content is included.

  The former pharmaceutical composition is preferably a pharmaceutical composition that does not contain one herbal ingredient selected from Bow Fu, Senkyu, Gypsum, Kaseki, and Toki. The icing method is a pharmaceutical composition that does not contain one herbal ingredient selected from Bow Fu, Senkyu, Gypsum, and Toki, and the amount of Kasseki is derived from Kasseki per 100% by weight of the pharmaceutical composition. The pharmaceutical composition is less than 100 ppm in terms of the aluminum content.

  In addition, the contents of Bow Fu, Senkyu, Gypsum, and Kasseki in the pharmaceutical composition of the present invention can be confirmed according to the methods described in Experimental Examples 1 (1) to (4) below. If the method does not detect the characteristic components contained in Bowfu, Senkyu, Gypsum, and Kasseki in the target pharmaceutical composition, or the physical / chemical properties based on the components are not recognized, It can be judged that the pharmaceutical composition of the present invention does not contain these herbal ingredients. In particular, with regard to casseki, the amount of components characteristic of the casseki is less than the amount of components contained in the conventionally known Futsutsu Seisaku, or the physical / chemical properties based on the components are conventionally known. In the case where it is smaller than the characteristics recognized by Fengtsu Sansho, it can be determined that the ratio of casserole contained in the pharmaceutical composition of the present invention is smaller than that of conventionally known Fudotsu Sanjo. Here, aluminum can be mentioned as a characteristic component of the casket. More specifically, when the content of aluminum is less than 100 ppm per 100% by weight of the final pharmaceutical composition, herbal medicine constituents (Falcon, Dai-o, Sanshi, Mao, Bow-sho, Forsythia, Sho-kyo) that make up Fufutsu Seisaku. , Ogon, Keigai, Kyaku, Hakka, Peonies, Peacocks, Senkyu, Gypsum, Bowfuu, Toki, and Kaseki). Can be distinguished from Seisaku.

  As shown in Experimental Example 2 to be described later, one of the above herbal medicine components of Fufutsu Seisaku, selected from Bow Fu, Senkyu, Gypsum, Kasseki, and Toki, preferably selected from Bow Fu, Kasseki, and Toki A pharmaceutical composition that does not contain one herbal medicine component that is not included, but contains all other herbal medicine ingredients (Food removal method), or all herbal medicine ingredients of Fufutsu Seisan, The pharmaceutical composition of the present invention in which the blending amount is less than the amount of kasseki contained in the conventionally known Fukatsu-san-san is superior in the effect of suppressing body weight gain than the conventionally-known Fukatsu-san-san (see Table 1). .

  In addition, as shown in Experimental Example 2, among the above-mentioned herbal medicine components of Fufutsu Seisaku, a pharmaceutical composition containing one herbal ingredient selected from Senkyu and Gypsum and other herbal medicine ingredients of Fufutsu Seisaku The product (pick-up agent) is more effective in suppressing fat accumulation in the internal organs (for example, the retroperitoneum, the testicles, the mesentery, the kidneys, etc.) than the conventionally known Fukatsu-san (see Fig. 1). reference).

  Also, as shown in Experimental Example 2, one of the above herbal components of Fufutsu Seisaku, one herbal component selected from Senkyu, Gypsum, Kasseki, and Toki, preferably one herbal medicine selected from Senkyu and Kasseki Even if it does not contain any ingredients (pick-up method), or contains all herbal medicine ingredients of Fufutsu Seisaku, the amount of Kasseki is less than the amount contained in the conventionally known Fufutsu Seisaku This pharmaceutical composition is superior in the effect of suppressing an increase in the amount of liver triglyceride than the conventionally known Fukatsutsu Seisaku (see FIG. 2).

  In addition, as shown in Experimental Example 2, among the above herbal components of Fufutsu Seisaku, one herbal component selected from Senkyu, Gypsum and Kasseki, preferably one herbal component selected from Senkyu and Kasseki, The pharmaceutical composition of the present invention that does not contain (one-pick-up method) or contains all of herbal medicine ingredients of Fufutsu Seisaku, of which the amount of Kasseki is less than the amount contained in the conventionally known Fufutsu Seisaku The composition is more excellent in the effect of suppressing the increase in the total cholesterol level in the liver than the conventionally known Fukatsu-Seisan (see FIG. 3).

  Furthermore, as shown in Experimental Example 2, among the above herbal components of Fukatsutsu Seisaku, one herbal component selected from Bow Fu, Kasseki, and Toki, preferably one herbal component selected from Kasseki, and Toki. The pharmaceutical composition of the present invention that does not contain (one-pick-up method) or contains all of herbal medicine ingredients of Fufutsu Seisaku, of which the amount of Kasseki is less than the amount contained in the conventionally known Fufutsu Seisaku The composition is more excellent in the effect of suppressing the increase in blood glucose level than conventionally known Fukatsutsu Seisaku (see FIG. 4).

  Furthermore, as shown in Experimental Example 2, it does not contain one herbal ingredient selected from Senkyu, Gypsum, and Kasseki among the above herbal ingredients of Fukatsutsu Seisaku (a flavourant), or Even if all the herbal medicine ingredients are included, the pharmaceutical composition of the present invention in which the amount of casseki is less than the amount contained in the conventionally known Fukatsu Seisaku is more bloody than the conventionally known Fudotsu Seiko. It is excellent in the effect of suppressing the increase in the intermediate insulin concentration (see FIG. 5).

When these results are combined, the following can be said.
The pharmaceutical composition of the present invention that does not contain either Senkyu or Gypsum among the above-mentioned herbal ingredients of Fukatsutsu Seisaku (pick-up method) is more effective in reducing body weight gain and body fat than conventionally known Fengtsu Seisaku. Excellent suppression of accumulation, suppression of increase in liver triglyceride level, suppression of increase in total liver cholesterol level, and / or suppression of increase in blood insulin concentration. From this result, even if either Fengshui Seiki is included in Feng Shui Seongsan, the amount of the blend is less than the amount contained in the conventionally known Fukatsu Seisan (for example, the blended amount is (Including a small amount of a pharmaceutical composition) is considered to have the same effect as the above-described pharmaceutical composition of the present invention, and can be handled in the same manner as the pharmaceutical composition of the present invention.

  Further, the present invention does not contain Kashiki among the above-mentioned herbal medicine ingredients of Fufutsu Seisaku (a flavour-eliminating agent), or even if it is contained, the blending amount thereof is less than the amount contained in the conventionally known Fufutsu Seisaku. The pharmaceutical composition of is more effective in suppressing body weight gain, body fat accumulation, liver triglyceride content, liver total cholesterol content, blood glucose level and blood insulin concentration Excellent suppression effect. Whether or not the pharmaceutical composition of the present invention has the above-described effects can be determined based on the content of aluminum, which is a characteristic component of Kasseki, contained in Fufutsu Seisaku. Specifically, of the above herbal medicine ingredients of Fukatsutsu Seisaku, it does not contain gusset (a taste-eliminating agent), or even if it is contained, the aluminum content is less than 100 ppm per 100% by weight of the final pharmaceutical composition In this case, it can be determined that the pharmaceutical composition of the present invention has the above effects. From the standpoint of effects, the aluminum content is preferably less, specifically 30 ppm or less, more preferably 20 ppm or less, still more preferably 15 ppm or less, and particularly preferably 11 ppm.

  In addition, the pharmaceutical composition of the present invention that does not contain toki among the above herbal medicine components of Fukatsu-san-san (a method for removing icing) is more effective in suppressing weight gain, increasing the amount of liver triglycerides than conventionally known Fukatsu-san-san, And / or excellent blood glucose level suppression effect. From this result, even in the case of Tofutsu Seisaku, even if it contains Toki, its blending amount is less than the amount contained in the conventionally known Futsutsu Seisaku (for example, a pharmaceutical with a very small amount of Toki). (Including the composition) is considered to have the same effect as the pharmaceutical composition of the present invention, and can be handled in the same manner as the pharmaceutical composition of the present invention.

  Furthermore, the pharmaceutical composition of the present invention that does not contain bowfish among the above herbal ingredients of Fukatsu-san-san (a method for removing icing) is more effective in suppressing weight gain and / or increasing blood sugar level than conventionally known Fukatsu-san-san. Excellent suppression effect. From this result, a pharmaceutical composition containing a small amount of boufufu, but less than the amount contained in the conventionally known boutsutsusansan (e.g., a pharmaceutical containing a very small amount of boufufu). (Including the composition) is considered to have the same effect as the pharmaceutical composition of the present invention, and can be handled in the same manner as the pharmaceutical composition of the present invention.

  Such a pharmaceutical composition of the present invention contains at least one herbal medicine selected from the group consisting of Bow Fu, Senkyu, Gypsum, Kaseki, and Toki, preferably one kind of herbal medicine is not blended, or the blending amount thereof is reduced. It can be prepared in accordance with conventionally known methods for preparing Fukatsu Sansho, such as selection of raw materials, proportions of herbal ingredients other than those described above, and formulation forms. The method for reducing the amount of Bow Fu, Senkyu, Gypsum, Kasseki, and / or Toki is not particularly limited. A method of reducing the amount of use of toki or preventing extraction or release from these plant materials and reducing extraction efficiency or release efficiency can be used. Although the latter method is not limited, for example, these plant raw materials used for extraction are used as they are, as they are, the degree of roughness is increased, the extraction time is shortened, or the extraction temperature is lowered. Or the like can be used. These may be carried out by selecting one alone or in combination of two or more in reducing the content of the herbal medicine.

  The form and shape of the pharmaceutical composition of the present invention can conform to the form and form of conventionally known Fengtsu Sansho. For example, as stipulated in the “Basic Handling Policy of Kampo Medicines” established by the Kampo Medicine Research Committee, the Kampo prescriptions (herbal medicine blends) described in the currently used Kampo-related letters and these Extracts and extract powders obtained from Kampo formulations are included. That is, the pharmaceutical composition of the present invention may use an extract (extract form) prepared by extraction from a plant raw material with a solvent, and the extract is formulated into a powder or granule by a conventional method. A so-called extract powder (extract powder form) and a tablet obtained by tableting this may be used. A preferable form is an extract powder form in which the extract is formulated into a powder or granule by a conventional method, or a tablet form obtained by compressing the extract.

  As a method for producing such extract powder, as an example of a pickle removal method, among the plant raw materials for preparing Fufutsu Seisaku, a kind selected from the group consisting of Bow Fu, Senkyu, Gypsum, Kasseki, and Toki is used. About 10 to 20 times the amount of water is added to the mixture of each plant raw material to be removed, and the mixture is stirred and extracted at about 80 to 100 ° C. for about 1 to 3 hours. Concentrate under reduced pressure to make dry extract powder by spray drying method, etc., or add appropriate adsorbent (eg silicic anhydride, starch etc.) to soft extract with increased extract concentration to make adsorbed extract powder A method is mentioned. In addition, an extract powder having a content of less than a predetermined amount selected from the group consisting of Bow Fu, Senkyu, Gypsum, Kasseki, and Toki is a mixture of each plant raw material used for extraction, Bow Fu, Senkyu, Gypsum, Kaseki, And the amount of one kind selected from the group consisting of Touki is less than the conventionally known Fudotsu Seisaku, or it is used as it is without chopping, or the degree of roughness is increased even if chopped, etc. It can manufacture by using the said plant raw material.

  The dosage of the pharmaceutical composition of the present invention can be appropriately changed depending on the patient's condition and the degree of symptom, but the daily dosage for one adult (body weight 60 kg) is the geniposides ( The amount is usually about 15 to 90 mg, preferably about 20 to 90 mg, more preferably about 25 to 90 mg in terms of the amount of geniposide or geniposide acid). The pharmaceutical composition of the present invention is prepared so as to satisfy the dose of the geniposides.

  The pharmaceutical composition of the present invention can be prepared in various dosage forms by combining the above active ingredients with pharmaceutically acceptable conventionally known carriers, excipients and the like.

  The pharmaceutical composition of the present invention is not limited as long as it is an oral administration form, and is a liquid preparation (including a suspension) such as a liquid (including syrup), a tablet, a pill, a powder, a fine granule, and a granule. Any of solid preparations such as tablets and capsules (including soft capsules) may be used.

  When the pharmaceutical composition of the present invention is in the form of a liquid preparation, it can be stored frozen, or it may be stored after removing water by lyophilization or the like. Freeze-dried preparations, dry syrups and the like are used by adding sterilized water and dissolving them again at the time of use.

  When the pharmaceutical composition of the present invention is in the form of a solid preparation, for example, in the case of a tablet, those conventionally known in the art can be widely used as a carrier. Examples of such carriers include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, silicic acid; water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin Binders such as solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, crystalline cellulose, hydroxypropylcellulose, hypromellose, sodium alginate; dry starch, agar powder, laminaran powder, sodium bicarbonate, polyoxyethylene sorbitan fatty acid Disintegrants such as esters, sodium lauryl sulfate, monoglyceride stearate, starch, crospovidone, povidone, low-substituted hydroxypropylcellulose; stearin, cocoa butter, water Disintegration inhibitors such as additive oils; Absorption accelerators such as quaternary ammonium salts and sodium lauryl sulfate; Moisturizers such as glycerin; Adsorbents such as starch, lactose, kaolin, bentonite and colloidal silicic acid; Purified talc and stearin Lubricants such as acid salts, boric acid powder and polyethylene glycol can be used. Further, the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets. Moreover, the composition containing the said active ingredient can be filled into the conventionally well-known capsule which uses gelatin, a pullulan, starch, gum arabic, hydroxypropyl methylcellulose (HPMC), etc. as a raw material, and can be set as a capsule.

  Moreover, when it is set as the form of a pill, a conventionally well-known thing can be widely used as a support | carrier in the said field | area. Examples include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin, ethanol, and disintegrants such as laminaran and agar. Can be used.

  In addition to the above, for example, surfactants, absorption promoters, adsorbents, fillers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure, dosage units of the preparations obtained It can be appropriately selected and used according to the form.

  Moreover, you may contain other active ingredients, such as an amino acid, vitamins, and organic acid salts. Examples of other active ingredients include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid , Amino acids such as hydroxylysine, arginine, ornithine, histidine; vitamins such as vitamin A1, vitamin A2, carotene, lycopene (provitamin A), vitamin B6, vitamin B1, vitamin B2, ascorbic acid, nicotinamide, biotin; Examples include alkali metal salts such as sodium chloride and potassium chloride, and organic acid salts such as citrate, acetate and phosphate.

  Any of these forms can be prepared by using ordinary methods in the field. For example, tablets may be prepared by appropriately adding the above active ingredients, insoluble dietary fiber and other excipients necessary for obtaining tablets, etc. It can be obtained by tableting after mixing and dispersing. The powder can be obtained by appropriately adding the above-mentioned active ingredients, insoluble dietary fiber and other excipients necessary for obtaining a powder, and mixing and powdering by a suitable method.

  The dosage of the pharmaceutical composition of the present invention can be appropriately set according to the dosage (dose per day) described in (4) above, and is usually divided into 2-3 times a day in the form of oral administration. Used. The dose time is not particularly limited, but is preferably before or between meals.

  The pharmaceutical composition of the present invention is usually about 1 to 10 g, preferably about 1.5 to 8 g, more preferably about 1.5 to 6 g as a dry extract per day for one adult (body weight 60 kg).

  The pharmaceutical composition of the present invention exhibits an excellent effect in suppressing or reducing weight gain and / or suppressing or reducing body fat accumulation. Therefore, the anti-obesity preparation of the present invention can be suitably used as an anti-obesity preparation (particularly an anti-visceral fat-type obesity preparation).

Visceral fat type obesity is a type of obesity in which fat accumulates around the viscera, and is recognized as a metabolic syndrome type obesity. The criteria for determining visceral fat type obesity are as follows: (i) “waist diameter is 85 cm or more for men, 90 cm or more for women” (ii) “visceral fat area by abdominal CT scan is 100 cm ^2. It is assumed that the above two conditions are satisfied. The Fengtsu Sansho of the present invention is also suitable for the prevention, improvement and / or treatment of metabolic syndrome caused by visceral fat accumulation.

  Hereinafter, the present invention will be described in more detail with reference to examples and the like, but the present invention is not limited thereto. In the following Examples, “part” means part by weight and “%” means weight% unless otherwise specified.

Experimental Example 1 Confirmation Test of Each Crude Drug Component (1) Bow Fu The test sample was powdered, 3 g was weighed, 15 mL of water was added and extracted with ultrasound for 5 minutes, and then 2 mL of aqueous ammonia (28) and 20 mL of diethyl ether were added. Shake well and centrifuge. The diethyl ether layer is separated and distilled off on a water bath, and the residue is dissolved in 1 mL of acetone to make a “sample solution”. Separately, cut the rhizome of “Boufuu” (windproof: Saposhnikovia divaricata), take 10 g of it, add 100 mL of water, extract it by heating (90-100 ° C.) for about 30 minutes after boiling, then filter while hot and concentrate the filtrate To make a soft extract. To this, 10 mL of water is added and extracted with ultrasonic waves for 5 minutes. Then, 2 mL of aqueous ammonia (28) and 20 mL of diethyl ether are added, and the mixture is shaken well and centrifuged. The diethyl ether layer is separated and distilled off on a water bath, and the residue is dissolved in 2 mL of acetone to make a “standard solution”. These two liquids are tested by thin layer chromatography. 10 μL of the sample solution and 5 μL of the standard solution are spotted on a thin layer plate prepared using silica gel for thin layer chromatography. Next, about 10 cm of development is performed using ethyl acetate / ethanol (99.5) / acetic acid (100) mixed solution (10: 1: 1) as a developing solvent, and then the thin layer plate is air-dried. When this is sprayed with dilute sulfuric acid, heated at 100 ° C. for 1 minute, and then irradiated with ultraviolet rays (main wavelength 365 nm), one of several spots obtained from the sample solution is obtained from the standard solution. When the color tone and the Rf value are the same as the spot emitting blue-white fluorescence near the Rf value of 0.4, it can be determined that the test sample contains bowfish. Further, the content of bow-fue contained in the test sample can be determined from the fluorescence intensity of the blue-white fluorescent spot near the Rf value of 0.4. In this case, the content of Bow Fu in the target test sample is compared with the content (known amount) of Bow Fu in the Wind-proof Tsusho-san measured using the conventionally known wind-proof Seiki-san as the test sample. It can be determined whether the amount is less than the known amount.

(2) Senkyu Powdered test sample, weigh 2 g, add 5 mL of water, shake and mix, add 2 mL of diethyl ether, shake well, centrifuge and separate the diethyl ether layer. This is referred to as “sample solution”. Separately, a 3- (3-hydroxy-4-methoxyphenyl) -2- (E) -propenoic acid / (E) -ferulic acid mixed reagent for thin layer chromatography is used as a “standard solution”. These two liquids are tested by thin layer chromatography. 20 μL of the sample solution and 2 μL of the standard solution are spotted on a thin layer plate prepared using silica gel for thin layer chromatography. Next, after developing about 10 cm using a mixed solution (5: 4: 2) of ethyl acetate / hexane / ethanol (99.5) as a developing solvent, the thin layer plate is air-dried. When a mixture of sulfuric acid / ethanol (99.5) (1: 1) is sprayed evenly on this and heated at 105 ° C. for 5 minutes and then irradiated with ultraviolet rays (main wavelength 365 nm), several pieces obtained from the sample solution If the color tone and the Rf value are the same as the spot that emits yellow fluorescence with an Rf value of about 0.4 obtained from the standard solution, the spot sample is judged to contain nematode. can do. Moreover, the content of the sensu in the test sample can be determined from the fluorescence intensity of the blue-white fluorescent spot having an Rf value of about 0.4. In this case, the content of Senkyu in the target test sample by comparing with the content (known amount) of Senkyu in the Windproof Sansho that has been measured using a conventionally known Futsutsu Seiki as the test sample It can be determined whether the amount is less than the known amount.

(3) Gypsum (sodium sulfate + hydrate)
The test sample is powdered and 1.7 g of it is ashed. After cooling, add 50 mL of dilute hydrochloric acid, shake well, and filter. Ammonia reagent solution is added to the filtrate to neutralize it and filtered. If a white white precipitate is formed immediately after adding a few drops of 0.5 mol / L barium chloride to 1 mL of this filtrate (qualitative reaction of sulfate (1)), gypsum (sodium sulfate + water in the test sample) Salt). In place of this method, the presence or absence of gypsum can also be measured and evaluated according to the Japanese Industrial Standard “Method for Chemical Analysis of Gypsum” (JIS R9101-1995).

(4) Kasseki (containing natural water-containing aluminum silicate and silicon dioxide)
By measuring the amount of aluminum contained in the test sample, it is possible to determine the presence or absence of kasseki in the test sample and the blending amount thereof. The aluminum content in the test sample can be measured by the following method based on the ICP emission analysis method.
(1) About 0.5 to 1 g of a test sample is weighed into a quartz beaker and ashed in an electric furnace at 500 ° C. (2) After completion of ashing, 20 ml of 20% strength aqueous hydrochloric acid solution is added and dissolved, and dried at 100 ° C.
(3) Add 5 ml of 10% hydrochloric acid and heat at 100 ° C. for 30 minutes.
(4) The obtained solution is filtered using filter paper and collected in a polypropylene container having a capacity of 50 ml.
(5) The amount of aluminum is calculated from the absorbance using an ICP emission analyzer under the following conditions.

[ICP emission analysis conditions]
Apparatus: ICP emission spectrometer (735-ES: Agilent Technologies)
RF output: 1600W
Plasma gas: 15L / min
Auxiliary gas: 1.5 L / min
Carrier gas: 0.55 L / min
Plasma observation direction: vertical direction Measurement wavelength: 167.019 nm.

  When aluminum is not detected, it is determined that no gusset is contained in the test sample. Further, the content of casserole contained in the test sample can be determined from the aluminum content. In addition, the content of Kasseki in the target test sample is compared with the aluminum content (known amount) in the windproof sansho that has been measured using a conventionally known Fudotsu Seiki as the test sample. It can be determined whether the amount is less than the known amount.

Experimental Example 2 Evaluation of anti-obesity effect using obesity model animal Fengtsu Sansho-san (Comparative Example), and a taste removal agent from which any one of Bow Fu, Senkyu, Gypsum, Kasseki, and Toki was removed (Example) 1-5) are orally administered to obese model mice, respectively, and the body weight, visceral fat weight, liver triglyceride amount, liver total cholesterol amount, blood glucose level, and blood insulin concentration are measured over time, and the pharmaceutical composition of the present invention The improvement effect on obesity (or metabolic syndrome) was evaluated.

1. Experimental method (1) Preparation of test sample (a) Futsutsu Seisaku extract (comparative example: conventional product)
The raw material herbs are as follows: Toki 1.2 (parts by weight, the same applies hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, Hakka 1.2, Showa 1.2, Keikei 1. 2, Bow Fu 1.2, Maou 1.2, Daio 1.5, Bow Shaw 1.5, Sandalwood 2.0, Kyo Kyo 2.0, Ogon 2.0, Licorice 2.0, Gypsum 2.0 and Kasseki Use at a ratio of 0, chop them, extract with 20 times the weight of water (560 parts by weight) at about 100 ° C. for 1 hour, centrifuge to obtain an extract, concentrate under reduced pressure and spray dryer And dried. The drying with a spray dryer was performed by dropping the extract into an atomizer with a rotation speed of 10,000 rpm and supplying hot air of 150 ° C. air.

(B) Wind-proof windproof Tsushosan extract (Example 1)
In the above-mentioned method for producing a wind-proof scented extract, a wind-proof wind-proof scented extract was prepared in the same manner except that no bow-fu was added.

(C) Senshu-extracted Futsutsu Seisaku Extract (Example 2)
In the manufacturing method of the above-mentioned windproof scented extract, a senkyu-extracted windproof scented extract was prepared in the same manner except that no senkyu was blended.

(D) Gypsum-extracted Futsutsu Seisaku Extract (Example 3)
In the manufacturing method of the above-mentioned wind-preventive scented extract, a gypsum-free wind-proof scented extract was prepared in the same manner except that no gypsum was added.

(E) Kaseki-extracted wind-proof tsushosan extract (Example 4)
In the manufacturing method of the above-mentioned wind-preventive sansho extract, the frost-extracted wind-preventive sansho extract was prepared in the same manner except that no mash was added.

(F) Windproof tsushosan extract without touki (Example 5)
In the manufacturing method of the above-mentioned wind-proof tsuyu-san extract, a wind-proof wind-proof san-san extract was prepared in the same manner except that no touki was added.

(2) Animal Experiments Mice (ICR mice, 4 weeks old, male) were fed with a high fat diet (D12492: Rodent Diet 60Kcal% Research Diets) for 5 weeks and bred to produce obese model mice. After measuring the body weight of this obese model mouse, a control group (control example), a wind-proof syosan administration group (comparative example), a bow-fu-free wind-proof syo-san administration group (Example 1), a senkyu-free wind-proof sang-san administration group (Example 2), Gypsum-extracted Fengtsu-san-san administered group (Example 3), Kasseki-extracted Feng-tsu-san-san-administered group (Example 4), and Sumoki-extracted Fengtsu-san-san group (Example 5) Divided into 7 groups (6-7 animals in each group).

  For each of these groups of obese model mice except the control group, each test sample was administered daily with a high fat diet for 4 weeks, and the body weight was measured once every two days. The control group was fed only a high fat diet without giving the test sample. Of the test samples, Fudotsu Seisaku (Comparative Example) is a rate of 2000 mg / kg body weight per day, and Examples 1 to 5 are obese model mice at a rate of 2200 mg / kg body weight per day. Administered orally. After 4 weeks, blood collection and organ fat were collected, and blood glucose level, blood insulin concentration, liver triglyceride level, total liver cholesterol level, and the amount of fat accumulated around the viscera (retroperitoneum, testis, mesentery, kidney) It was measured.

2. Experimental Results (1) Change in body weight Table 1 shows the rate of change in body weight measured for each obesity model mouse before administration of the test sample (initial), on the 10th, 20th, and 28th days of administration. The rate of change is calculated by converting the body weight after sample administration of each obese model mouse into a relative value when the initial body weight is 100, and further increasing or decreasing based on the body weight of the Fengtsu Sansho administration group (comparative example). In order to evaluate it, it converted into the relative value when the body weight on the 10th day, the 20th day and the 28th day of administration of the Fadotsu Seisaku administration group is 100.

  As can be seen from this, the wind-proof tsusho-san without bowfish (Example 1), the wind-proof tsusho-san without gypsum (Example 2), the wind-proof tsusho-san without gypsum (Example 3), and the wind-proof tsusho-san without gusset (Example) 4), and the wind-breaking windproof sansho (Example 5) both were more effective in suppressing weight gain than the windproof sansho (comparative example). Among them, the windbreaker Seikisan (ex. 1) without boufufu (Example 1), the wind-preventive sanctuary without gusset (Example 4), and the wind-preventive Sanjo Sanki (Example 5) have excellent weight gain suppression effects. found.

(2) Visceral fat weight FIG. 1 shows the fat weight (g) around the viscera (retroperitoneum, testis, intestine, kidney) of each obese model mouse 4 weeks after sample administration. In FIG. 1, the fat weight (g) around the peritoneum, around the testis, between the intestines, and around the kidney, and the total amount (g) thereof are shown in order from the left side for each sample administration group. As can be seen from FIG. 1, the windbreaker Seikisan without bowfish (Example 1), the windbreaker Seisakusen without gypsum (Example 2), the windbreaker Seikisan without gypsum (Example 3), Among the examples 4) and the cypress-extracted wind-proof tsusan-san (Example 5), the senkyu-extracted wind-proof tsusan-san (Example 2) and the gypsum-extracted wind-proof san-san (Example 3) The effect of suppressing fat accumulation in the internal organs was superior to Seiki (comparative example).

(3) Amount of liver triglyceride FIG. 2 shows the amount of liver triglyceride (mg / g) of each obese model mouse 4 weeks after administration of the sample. As can be seen from FIG. 2, the wind-proof tsusho-san without bow (Example 1), the wind-proof tsuyo-san with senkyu (Example 2), the gypsum-free tsutsu-san (Example 3), Among the examples 4) and the cypress-extracted wind-proof tsusan-san (Example 5), the senkyu-extracted wind-proof tsusan-san (Example 2), the gypsum-excluded wind-proof sansho-san (Example 3), and the kasseki-exclusive wind-proof santo-san. Yuki-san (ex. 4), and cypress-extracted wind-proof tsusan-san (example 5). San (Example 4) was superior in the effect of suppressing the increase in the amount of liver triglyceride than Fengtsu Seisaku (Comparative Example).

(4) Total Liver Cholesterol FIG. 3 shows the total liver cholesterol (mg / g) of each obese model mouse 4 weeks after sample administration. As can be seen from FIG. 3, the windbreaker Seiki-san (ex. 1) without sensation, the wind-prevent sanjo-san (ex. Among the examples 4) and the cypress-extracted wind-proof tsusan-san (Example 5), the senkyu-extracted wind-proof tsusan-san (Example 2), the gypsum-excluded wind-proof tsusan-san (Example 3), and the gusset-free wind-proof Seisaku (Example 4), especially Senkyu-free Fufutsu Seisaku (Example 2), and Kasseki-futsu Futsutsu Seisaku (Example 4) have a higher total liver cholesterol level than Fufutsu Seisaku (Comparative Example). The effect of suppressing the increase was excellent.

(5) Blood glucose level FIG. 4 shows the blood glucose level (mg / dl) of each obese model mouse 4 weeks after administration of the sample. As can be seen from FIG. 4, the windbreaker Seikisan without bow (Example 1), the windbreaker Seisakusen without gypsum (Example 2), the windbreaker Seikoku without gypsum (Example 3), Among the examples 4) and the cypress-extracted wind-proof tsusan-san (example 5), Seisaku (Example 5), in particular, Kaseki-free Fuyutsu-sho-san (Example 4), and Touki-no-futsu-tsutsu-san (Example 5) increase blood sugar levels more than Fufutsu Seisaku (Comparative Example). Excellent suppression effect.

(6) Blood Insulin Concentration FIG. 5 shows the blood insulin concentration (ng / ml) of each obese model mouse 4 weeks after sample administration. As can be seen from FIG. 5, the windbreaker Seikisan without bowfish (Example 1), the windbreaker Seisakusen without gypsum (Example 2), the windbreaker Seikisan without gypsum (Example 3), Among the examples 4) and the cypress-extracted wind-proof tsusan-san (Example 5), the senkyu-extracted wind-proof tsusan-san (Example 2), the gypsum-excluded wind-proof tsusan-san (Example 3), and the gusset-free wind-proof tsutsu-san Seisaku (Example 4) was superior in the effect of suppressing an increase in blood insulin concentration than Fengtsu Seisaku (Comparative Example).

Examples 6-8
According to the following method, the blending amount of Kaseki in Feng Shui-san was prepared, and Fukatsu-Dori (Examples 6 to 8) having an aluminum content of less than 100 ppm was prepared.

(1) Preparation of Fengtsu Sansho-san extract As described below, change the shape of Kasseki used for extraction to prepare a Fengtsu-san Seiki extract, which contains Kasseki (containing natural hydrous aluminum silicate and silicon dioxide) The aluminum content derived from the product was determined. The aluminum content was measured using the ICP emission analyzer shown in Experimental Example 1.

(2) Preparation of Fufutsu Seisaku Extract (Comparative Example) According to the conventional method, using the powdered casserole, a windproof tsuusan extract was prepared by the following method.

  The raw material herbs are as follows: Toki 1.2 (parts by weight, the same applies hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, Hakka 1.2, Showa 1.2, Keikei 1. 2, Bow Fu 1.2, Maou 1.2, Daio 1.5, Bow Shaw 1.5, Sandalwood 2.0, Kyo Kyo 2.0, Ogon 2.0, Licorice 2.0, Gypsum 2.0 and Kasseki Use at a ratio of 0, chop them, extract with 20 times the weight of water (560 parts by weight) at about 100 ° C. for 1 hour, centrifuge to obtain an extract, concentrate under reduced pressure and spray dryer And dried. The drying with a spray dryer was performed by dropping the extract into an atomizer with a rotation speed of 10,000 rpm and supplying hot air of 150 ° C. air.

  The aluminum content contained in the thus-prepared Futsutsu Seisan dried extract (conventional product) was measured and found to be 100 ppm.

(3) Preparation of Kyutsutsu Seisaku dried extract (Examples 6 to 8) Instead of the above-mentioned Kasseki, the original Kassaki (substantially cubic shape with a side of about 2 cm), the original mass was roughly crushed Using a large lump (approximately 1 cm on a side) and a small lump (approximately 3 mm on a side) obtained by pulverizing the original lump in the same manner as above A windproof tsusansan dried extract was prepared. When the aluminum content contained in the thus-prepared Futsutsu-san-san extract was measured using an ICP emission spectrometer, it was found that the dried Futsu-san-san extract (Example 6) was prepared using the raw lump. The aluminum content is 1 ppm, the aluminum content contained in Fengtsu Seisan dried extract (Example 7) prepared using a large lump of coarse crushed crumbs is 2 ppm, and the lumps are finely crushed into small pieces The content of aluminum contained in the dry extract of Fengtsu Sansho-san (Example 8) prepared using a lump of lump was 11 ppm.

Experimental Example 3 Evaluation of fat reduction effect using fat cells Fukutsutsu-sansho-san extract without casket prepared above (Example 4: Aluminum content 0 ppm), Fudotsu-sansan dry extract (Example 6: Aluminum content 1 ppm, implementation) Example 8: The aluminum content was 11 ppm), and Fengtsu Sansho extract (comparative example: aluminum content: 100 ppm) was used to evaluate the effect of reducing accumulated fat in fat cells. Specifically, the adipocytes are cultured in the presence of each test sample, and the test sample is compared with the fat cells cultured in the absence of the test sample (control) and the amount of fat accumulated in the fat cells. The fat reduction effect by was evaluated.

1. Experimental method (1-1) Preparation of test sample About 620 mg of each of the above-mentioned wind-proof Tsushosan extract was added, 10 mL of water was added, and the mixture was dissolved by ultrasonic irradiation for 30 minutes using 60 ° C hot water. After centrifugation (3000 rpm, 10 minutes), the supernatant was filtered sequentially with two types of 0.45 μm filters (25mm GD / X CAT # 6872-2504 / whatman and 25mm GHP ACRODISCCAT # 4560 / PALL). The solution was filtered through a 0.2 μm sterilizing filter, and the filtrate was recovered as a sample stock solution. The collected sample stock solution was diluted 5-fold with a cell culture medium, and further the following experiment was performed using a test solution prepared by diluting the sample stock solution 6-fold with the same medium as a test sample.
[Test sample]
(A) Aluminum content 0 ppm Windproof Tsushosan Extract: Example 4
(B) Aluminum content 1 ppm
(C) Aluminum content 11 ppm
(D) Aluminum content 100 ppm

(1-2) Preparation of cells
(1) The frozen 3T3-L1 cells were thawed and cultured in a 5% carbon dioxide gas-air, saturated water vapor, 37 ° C. environment using a cell culture medium. In addition, DMEM containing antibiotics (penicillin, streptomycin, HEPES) and 10% FBS was used as a cell culture medium.
(2) After confirming that the cultured cells were 80% confluent, the medium was removed, and the cells adhering to the bottom of the cell culture flask were removed with a trypsin-EDTA solution.
(3) The cells were seeded in a 96-well plate so that the number of cells was 3 × 10 ⁴ cells / well, and cultured at 37 ° C. in a cell culture medium. After confirming that the cells were 100% confluent (about 2 days after the start of culture), the cells were further cultured at 37 ° C. for 2 days.
(4) Next, the cell culture medium was removed, 200 μl / well of each test sample diluted 30-fold with differentiation induction medium was added to each well, and cultured at 37 ° C. for 3 days. As the differentiation induction medium, IBMX (Cell-Based Assay IBMX Solution (1,000X), Insulin (Adipogenesis Assay Insulin Solution (1,000X)), and DEX (Adipogenesis Assay Dexamethasone Solution (1,000X)) per 10 ml of the above cell culture medium. Each of these reagents is an accessory reagent of Adipogenesis Assay Kit (Cayman CHEMICAL).
(5) After each test sample is cultured in a differentiation induction medium diluted, the medium is removed, and each test sample is diluted 30-fold with differentiation induction medium to each well, and each test sample is 200 μl / well. After each addition, the cells were cultured at 37 ° C. for 2-3 days. Thereafter, the medium was replaced with insulin (differentiation) medium, and each test sample diluted 30-fold with insulin (differentiation) medium was cultured again at 37 ° C. for 2 days. As the insulin (differentiation) medium, a medium in which 10 μl of insulin (Adipogenesis Assay Insulin Solution (1,000 ×)) was added per 10 ml of the cell culture medium was used.
(6) After each test sample was cultured in a diluted insulin (differentiation) medium, the medium was removed, replaced with a cell culture medium, and cultured at 37 ° C. for 2 days.
(7) After completion of the culture, it was confirmed that the cells had changed (differentiated) into a fat cell morphology, and this was used as a fat cell in the following staining test.

(1-3) Staining Test The reagent used in the series of tests (1) to (6) below is an accessory reagent of Adipogenesis Assay Kit (Cayman CHEMICAL).
(1) After preparing adipocytes by the method described in (1-2) above, the cell culture medium was removed from each well of the 96-well plate. Next, 75 μl of Fixative was added to each well and incubated at 37 ° C. for 15 minutes. Fixative was prepared by adding 10 μl of Fixative (Lipid Droplets Assay Fixative (10X)) to 90 ml of PBS of pH 7.2.
(2) Each well was washed twice every 5 minutes with 100 μl of Wash Solution (Lipid Droplets Assay Wash Solution), and the wells were dried after washing.
(3) 75 μl of Oil Red O solution (Lipid Droplets Assay Oil Red O solution) was added to each well and incubated at 37 ° C. for 20 minutes.
(4) Next, Oil Red O solution was removed and washed with distilled water 2-3 times until the pink color disappeared. In addition, the wells were washed twice every 5 minutes with 100 μl of Wash Solution.
(5) After washing, the wells were completely dried, and 100 μl of Dye Ectraction solution was added to each well and gently mixed for 30 minutes.
(6) Next, the absorbance (absorbance of the test sample addition group) was measured for each well at a wavelength of 520 nm. From the comparison with the absorbance of fat cells (control) cultured in the absence of the test sample, Calculate the rate of reduction of fat accumulated in the cells. In addition, the absorbance used in the following calculation formula is a value obtained by averaging the test results with N = 3.

  Furthermore, the addition of other test samples when the fat reduction rate of the test sample addition group using Windproof Tsushosan extract (comparative example) (test sample (d)) having an aluminum content of 100 ppm as the test sample is 100. The relative value ((test sample (a)-(d)) / (test sample (d)) × 100) of the fat reduction rate of the group (test sample (a)-(c)) was calculated. The results are shown in FIG.

2. Experimental results As shown in FIG. 6, the lower the ratio of casket in the traditional windbreak, the lower the ratio of casket in the conventional windbreak, less specifically 100 ppm in terms of aluminum content, especially It has been found that the smaller the amount is 11 ppm or less, the higher the effect of reducing the wind-breaking sansho to fat accumulated in fat cells. Therefore, a pharmaceutical composition that removes casket from the traditional windproof sansho (a flavour-eliminating agent) or has a reduced casket content than the conventional windproof sansho is more It is excellent in the effect of suppressing fat accumulation, the effect of suppressing or improving obesity, and the effect of suppressing weight gain.

Claims (6)

Of the herbal medicines that make up Fengshui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoukyo, mint, peonies, peony, senkyu, gypsum, boufu, touki, and caseki) Including at least one herbal ingredient other than at least one herbal ingredient selected from the group consisting of cucumber, cucumber, gypsum, gypsum, gusset, and toki, The pharmaceutical composition, which is less than 100 ppm in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition. All of the herbal medicine components that constitute the above-mentioned Fukatsu Sansho, and the compounding amount of Kasseki is 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition, The pharmaceutical composition according to 1. Of the herbal medicine components that make up Feng Shui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoto, mint, peonies, peacock, senkyu, gypsum, boufu, touki, caseki) Including at least one herbal ingredient other than at least one herbal ingredient selected from the group consisting of boufu, senkyu, gypsum, and touki, and the blended amount of casseki is derived from Kasseki per 100% by weight of the pharmaceutical composition A pharmaceutical composition characterized by being less than 100 ppm in terms of aluminum content. The pharmaceutical composition according to claim 3, wherein the blending amount of casseki is 11 ppm or less in terms of aluminum content derived from casseki per 100% by weight of the pharmaceutical composition. Of the herbal medicine components that make up Feng Shui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoto, mint, peonies, peacock, senkyu, gypsum, boufu, touki, caseki) The other herbal ingredients except for at least one herbal ingredient selected from the group consisting of boufu, senkyu, gypsum, kasseki, and toki are included, or all of the herbal ingredients are included, and The pharmaceutical composition according to claim 1 or 2, comprising a step of preparing an extract of the herbal medicine component so that it is less than 100 ppm or 11 ppm or less in terms of the aluminum content derived from Kasseki per 100% by weight of the pharmaceutical composition. Manufacturing method. Of the herbal medicine components that make up Feng Shui Sansou (licorice, daiou, sanshishi, maou, bowsho, forsythia, ginger, ogon, keigai, kyoto, mint, peonies, peacock, senkyu, gypsum, boufu, touki, caseki) Including at least one herbal ingredient other than at least one herbal ingredient selected from the group consisting of boufu, senkyu, gypsum, and touki, and the blended amount of casseki is derived from Kasseki per 100% by weight of the pharmaceutical composition The manufacturing method of the pharmaceutical composition of Claim 3 or 4 including the process of preparing the extract of the said herbal medicine component so that it may become less than 100 ppm or 11 ppm or less in conversion of aluminum content.