US 20140050805A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0050805 A1 Kambayashi et al. (43) Pub. Date: Feb. 20, 2014

(54) COMPOSITION, GLUCOSE (30) Foreign Application Priority Data METABOLISM-IMPROVINGAGENT, AND METHOD FOR IMPROVING GLUCOSE Apr. 15, 2011 (JP) ...... 2011-091461 METABOLISM Publication Classification

(75) Inventors: HiroakiO O Kambayashi, Tokyo (JP); (51) A61E36/67Int. Cl. (2006.01) Murakoshi, Tokyo (JP) A613 L/58 (2006.01) A61E36/258 (2006.01) (73) Assignee:------Lion Corporation, Tokyo (JP) (52) U.S.CPC Cl...... A61K 36/67 (2013.01); A61K 36/258 (21) Appl. No.: 14/111,576 (2013.01); A61 K3I/51 (2013.01); A61 K3I/58 (2013.01) (22) PCT Filed: Apr. 2, 2012 USPC ...... 424/728; 424/734 (57) ABSTRACT (86). PCT No.: PCT/UP2012/058819 A composition, including: (A) Panax notoginseng, and at S371 (c)(1), least one of (B) a Piper longum extract and (C) vitamin B1, a (2), (4) Date: Oct. 14, 2013 salt thereof or a derivative thereof. US 2014/0050805 A1 Feb. 20, 2014

COMPOSITION, GLUCOSE SUMMARY OF INVENTION METABOLISM-IMPROVINGAGENT, AND METHOD FOR IMPROVING GLUCOSE Technical Problem METABOLISM 0010. The present invention aims to solve the above exist ing problems and achieve the following objects. Specifically, TECHNICAL FIELD an object of the present invention is to provide: a composition having excellent glucose metabolism-improving effects, hav 0001. The present invention relates to: a composition suit ing high safety, and capable of being conveniently used, a ably used for improving glucose metabolism; a food, a bev erage, a pharmaceutical drug, a glucose metabolism-improv food, a beverage, a pharmaceutical drug, a glucose metabo ing composition and a glucose metabolism-improving agent, lism-improving composition and a glucose metabolism-im each of which contains the composition; and a method for proving agent, each of which contains this composition; and improving glucose metabolism. a method for improving glucose metabolism. Solution to Problem BACKGROUND ART 0011. The present inventors conducted extensive studies 0002. In recent years, Japanese have gradually been obese to solve the above problems and have obtained the following because their dietary habits have been high-fat and high findings. Specifically, they have found that a composition caloric, for example. It has been Suggested that impaired containing: (A) Panax notoginseng and at least one of (B) a glucose tolerance, high blood pressure, and so on are greatly Piper longum extract and (C) vitamin B1, a salt thereof or a related to not only genetic factors but also environmental derivative thereof, has excellent glucose metabolism-improv factors such as obesity. When the metabolic pathway of glu ing effects, has high safety, and is capable of being conve cose in the process using glucose as energy does not work niently used. The present invention has been accomplished on normally due to, for example, obesity and as a result failures the basis of this finding. to metabolize glucose occur Such as inhibition of use of 0012. The present invention is based on the above finding glucose, chronic hyperglycemic condition is caused. Such obtained by the present inventors, and a means for Solving the chronic hyperglycemic condition causes systemic vascular above problems is a composition containing: (A) Panax noto disorders and may further cause complicating diseases Such ginseng, and at least one of (B) a Piper longum extract and (C) as nerve disorders and retinopathy, which is problematic. vitamin B1, a salt thereof or a derivative thereof. 0003. One possible measure to prevent or improve obesity is improving daily habits. However, improving daily habits Advantageous Effects of Invention by themselves are often difficult to continue. Therefore, 0013 The present invention can provide: a composition demand has arisen for simple and effective prevention or having excellent glucose metabolism-improving effects, hav improvement of glucose metabolism. ing high safety, and capable of being conveniently used, a 0004 Proposed means of improving glucose metabolism food, a beverage, a pharmaceutical drug, a glucose metabo include: compositions containing panaxadiol (PD) and/or lism-improving composition and a glucose metabolism-im panaxatriol (PT) contained in Panax notoginseng (see PTLs 1 proving agent, each of which contains this composition; and and 2); a composition containing Panax notoginseng or an a method for improving glucose metabolism. These can solve extract thereof irradiated with microwaves (see PTL 3); and the above existing problems and achieve the above objects. granulated products formed by granulating dry powder of Panax notoginseng, dry powder of lingzhi , and DESCRIPTION OF EMBODIMENTS dry powder of agaricus mushroom (see PTL 4). Composition 0005. However, even use of these proposed compositions does not exhibit sufficient glucose metabolism-improving 0014. A composition of the present invention contains at effects. Hence, at present, there is a need to provide: a com least: (A) Panax notoginseng, and at least one of (B) a Piper position having more excellent glucose metabolism-improv longum extract and (C) vitamin B1, a salt thereof or a deriva ing effects, having high safety, and capable of being conve tive thereof, and, if necessary, further contains other ingredi niently used, a food, a beverage, a pharmaceutical drug, a entS. glucose metabolism-improving composition and a glucose 0015 The state of the above composition is not particu metabolism-improving agent, each of which contains this larly limited and may be appropriately selected depending on composition; and a method for improving glucose metabo the intended purpose. Examples thereof include a liquid state, lism. a solid state and a semi-solid state. <(A) Panax notoginseng> CITATION LIST 0016. The Panax notoginseng (denshichi ninjin, also called sanshichi ninjin) (hereinafter may be referred to as Patent Literature “ingredient (A)) is a plant belonging to the genus Panax of the family Amliaceae. 0006 PTL 1: Japanese Patent Application Laid-Open (JP 0017. The Panax notoginseng may be used as is after it has A) No. 2011-026314 been harvested from the natural world. Alternatively, the 0007 PTL 2: JP-A No. 2011-0263.13 Panax notoginseng may be one obtained after its natural product has been Subjected to treatments such as washing, 0008 PTL3: JP-A No. 2002-114696 drying, cutting, Smashing and milling, which are appropri 0009 PTL 4: JP-A No. 2000-143526 ately combined together, and the thus-treated product has US 2014/0050805 A1 Feb. 20, 2014 been extracted, purified and/or fermented. A commercially selected depending on the intended purpose, but is preferably available product may be used as the Panax notoginseng. 0.04% by mass to 16% by mass, more preferably 2% by mass 00.18 Examples of the commercially available product to 12% by mass. When the concentration of the acid in the include Panax notoginseng powder and Panax notoginseng aqueous acid solution is less than 0.04% by mass, the aqueous extract powder (these products are of MATSUURA hydrolysis is not sufficiently performed and as a result at least YAKUGYO CO.,LTD.). one of panaxadiol and panaxatriol may not be formed. 0019. In particular, from the viewpoint of obtaining the Whereas when it is more than 1.6% by mass, the hydrolysis glucose metabolism-improving effects, the Panax notogin may excessively proceed and there may be a disadvantage in seng is preferably an extract obtained by extracting its powder terms of cost. with a solvent, more preferably an acid-treated product 0028. The amount of the aqueous acid solution used is not thereof, particularly preferably an acid-treated product con particularly limited and may be appropriately selected taining at least one of panaxadiol (PD) and panaxatriol (PT) at depending on the intended purpose. It is preferably 2 times by a high concentration. volume to 20 times by volume relative to the Panax notogin 0020. The panaxadiolor panaxatriol is an aglycon formed Seng. When the amount of the aqueous acid solution used is after the Sugar moiety has been removed from Saponin (gly less than 2 times by Volume relative to the Panax notoginseng, coside) of the Panax notoginseng and then the side chain has the Panax notoginseng is not sufficiently immersed in the been ring-closed. It is formed by Subjecting the Panax noto aqueous acid solution and as a result the hydrolysis cannot ginseng to acid treatment. sufficiently be conducted. Whereas when it is more than 20 0021. The acid-treated product containing at least one of times by Volume, there may be a disadvantage in terms of the panaxadiol and the panaxatriolata high concentration can COSt. exhibit excellent metabolism-improving effects. The acid 0029. The lower alcohol is not particularly limited and treated product containing a mixture of the panaxadiol and may be appropriately selected depending on the intended the panaxatriol at a high concentration can exhibit more purpose. Examples thereof include methanol, ethanol and excellent glucose metabolism-improving effects, which is propanol. These may be used alone or in combination of two advantageous. or more thereof. Among them, ethanol is preferred interms of 0022. The total amount of the panaxadiol and the panaxa safety. triol in the ingredient (A) is not particularly limited and may 0030. When the lower alcohol is used as an aqueous solu be appropriately selected depending on the intended purpose, tion containing the lower alcohol, the mixing ratio between but is preferably 0.1% by mass or more, more preferably 0.1% water and the lower alcohol is not particularly limited and by mass to 50% by mass, still more preferably 1% by mass to may be appropriately selected depending on the intended 50% by mass, particularly preferably 10% by mass to 30% by purpose. The mixing ratio by volume of water the lower a SS. alcohol is preferably 9:1 to 2:1, more preferably 3:1. 0023 The amount of the panaxadiol or the panaxatriol in 0031. The amount of the lower alcohol used is not particu the ingredient (A) can be measured through gas chromatog larly limited and may be appropriately selected depending on raphy using commercially available panaxadiol or panaxa the intended purpose. It is preferably 1% by volume to 80% triol as a standard Substance. by volume, more preferably 10% volume to 50% by volume, particularly preferably 20% by volume to 40% by volume, > relative to the total amount of the hydrolyzation liquid. When the amount of the lower alcohol used is less than 1% by 0024. The method for producing the acid-treated product volume relative to the total amount of the hydrolyzation liq is not particularly limited and may be appropriately selected uid, sapogenins may not efficiently beformed. Whereas when depending on the intended purpose. One preferred method it is more than 80% by volume, at least one of panaxadiol and includes: a hydrolyzing step of hydrolyzing the Panax noto panaxatriol may not efficiently be formed and there may be a ginseng with an aqueous acid solution; a neutralizing step of disadvantage in terms of cost. neutralizing the liquid obtained after the hydrolysis; a filtrat 0032. Notably, the “total amount of the hydrolyzation liq ing step of filtrating the neutralized liquid; and a drying step uid refers to the total amount of the reaction liquid contain of drying the residue after the filtration. The method ing the aqueous acid solution and the lower alcohol. described in International Publication No. WO2010/029915 0033. The temperature at which the hydrolysis is per can be employed as the method for producing the acid-treated formed is not particularly limited and may be appropriately product of the Panax notoginseng. selected depending on the intended purpose. It is preferably 60° C. to 100° C., more preferably 70° C. to 90° C. —Hydrolyzing Step— 0034. The time for which the hydrolysis is performed is 0025. The hydrolyzing step is a step of hydrolyzing the not particularly limited and may be appropriately selected Panax notoginseng with an aqueous acid solution, and is depending on the intended purpose. It is preferably 0.5 hours preferably performed in the presence of a lower alcohol. to 24 hours, more preferably 2 hours to 8 hours. 0026. The aqueous acid solution is not particularly limited and may be appropriately selected depending on the intended —Neutralizing Step— purpose. Examples thereof include aqueous Solutions con 0035. The neutralizing step is a step of neutralizing the taining inorganic acids such as hydrochloric acid, phosphoric hydrolyzed liquid obtained from the hydrolysis. acid, Sulfuric acid and nitric acid. These may be used alone or 0036. The method for the neutralization is not particularly in combination of two or more thereof. Among them, an limited and may be a known method. Examples thereof aqueous solution containing hydrochloric acid is preferred. include a method in which an aqueous solution of a base Such 0027. The concentration of the acid in the aqueous acid as Sodium hydroxide or potassium hydroxide is appropriately Solution is not particularly limited and may be appropriately added to the hydrolyzed liquid. US 2014/0050805 A1 Feb. 20, 2014

0037. Notably, the pH of the liquid after the neutralization 0047. The solvent used for the extraction is not particu is not particularly limited and may be appropriately selected larly limited and may be appropriately selected depending on depending on the intended purpose. The pH thereof is pref the intended purpose. Examples thereof include water, etha erably 5 to 8. nol and a mixture thereof. 0048. The extraction temperature at which the above —Filtrating Step— extraction is performed is not particularly limited and may be appropriately selected depending on the intended purpose, 0038. The filtrating step is a step of filtrating the hydro but is preferably 25° C. to 95°C., more preferably 40° C. to lyzed liquid after the neutralizing step, to thereby be sepa 800 C. rated into a filtrate and a residue. 0049. The extraction time for which the above extraction 0039. The method for the filtration is not particularly lim is performed is preferably 0.1 hours to 12 hours, more pref ited and may be appropriately selected from known methods. erably 0.5 hours to 4 hours. Notably, after the filtration, the obtained product may be 0050. Among them, the ingredient (B) is particularly pref repeatedly washed with water until the salts are completely erably a hot water extract of Piper longum. removed. The washing with water is preferred also interms of 0051 Specific examples of the commercially available being able to reduce the concentration of ethanol. product of the ingredient (B) include LONG PEPPER EXTRACT POWDERMF (trade name) (composition: 10% —Drying Step— by mass of a hot water extract of Piper longum, 90% by mass of dextrin, product of MARUZEN PHARMACEUTICALS 0040. The drying step is a step of drying the residue after CO.,LTD.). the filtration. 0.052 The amount of the ingredient (B) in the above com 0041. The method for the drying is not particularly limited position is not particularly limited and may be appropriately and may be appropriately selected from known methods. selected depending on the intended purpose, but is preferably Examples thereof include freeze drying, air-circulation dry 0.1% by mass to 20% by mass, more preferably 1% by mass ing, reduced-pressure drying, spray drying and heating dry to 10% by mass. 1ng. 0053. The mass ratio ((A):(B)) of the ingredient (A) and 0042. The amount of the ingredient (A) in the above com the ingredient (B) in the above composition is not particularly position is not particularly limited and may be appropriately limited and may be appropriately selected depending on the selected depending on the intended purpose, but is preferably intended purpose, but is preferably 1:100 to 1,000:1, more 3% by mass or more, more preferably 3% by mass to 70% by preferably 1:10 to 100:1, particularly preferably 1:2 to 20:1. mass, particularly preferably 6% by mass to 64% by mass. 0054 When the mass ratio (A):(B)) falls within the above When the amount of the ingredient (A) is less than 3% by preferred range, advantageously, more excellent glucose mass, the glucose metabolism-improving effects may not be metabolism-improving effects can be obtained. obtained. <(B) Piper longum Extract <(C)Vitamin B1, a Salt Thereof, or a Derivative Thereof) 0043. The Piper longum extract (hereinafter may be 0055. The vitamin B1, salt thereof or derivative thereof referred to as “ingredient (B)') is not particularly limited and (hereinafter may be referred to as “ingredient (C)") is a com may be appropriately selected depending on the intended pound called thiamine having a molecular formula of purpose so long as it is an extract of Piper longum. CHNOS, a salt thereof, or a derivative thereof. 0056. The salt of the vitamin B1 is not particularly limited 0044 Piper longum is an evergreen vine distributed in the and may be appropriately selected depending on the intended Southeast Asia and belonging to the genus Piper of the family purpose. Examples thereof include thiamine hydrochloride, Piperaceae. Its spike becomes a fleshy, thick, cylindrical thiamine nitrate, thiamine dicetylsulfate, thiamine thiocyan shape, and is used as a condiment. The part of the Piper ate, thiamine naphthalene-1,5-disulfonate, thiamine dilauryl longum used for the extraction in the present invention is not sulfate, thiamine disulfide, bisthiamine nitrate, and salts of particularly limited and may be appropriately selected thiamine dicetylsulfate esters. depending on the intended purpose. Examples thereof 0057 The derivative of the vitamin B1 is not particularly include spike, roots, leaf, stem, flower, and parts containing limited and may be appropriately selected depending on the these in combination. Among them, spike is particularly pre intended purpose. Examples thereof include fursultiamine ferred. hydrochloride, dibenzoylthiamine, octothiamine, bisibuthia 0045. The ingredient (B) does not exhibit the glucose mine, bisbentiamine, benfothiamine, dicethiamine hydro metabolism-improving effects alone. However, when the chloride and cycotiamine. ingredient (B) and the ingredient (A) are used in combination, 0058. These may be used alone or in combination of two or advantageously, the glucose metabolism-improving effects more thereof. Among them, thiamine nitrate and thiamine of the ingredient (A) can be further improved, although its hydrochloride are preferred. mechanism is not known. 0059. When the ingredient (C) and the ingredient (A) are 0046. The method for extracting the ingredient (B) is not used in combination, advantageously, the glucose metabo particularly limited and may be appropriately selected lism-improving effects of the ingredient (A) can be further depending on the intended purpose. Examples thereof improved, although its mechanism is not known. include a method of extracting it with a solvent. The extract 0060. The method for obtaining the ingredient (C) is not may be subjected to treatments such as purification and fer particularly limited and may be appropriately selected mentation, or may be dried. Also, a commercially available depending on the intended purpose. Examples thereof product may be used as the ingredient (B). include: a method of extracting it from vitamin B1, a salt US 2014/0050805 A1 Feb. 20, 2014

thereof, or a derivative thereof; and a method of synthesizing 0070 The preserving agent is not particularly limited and it. Alternatively, a commercially available product may be may be appropriately selected depending on the intended used as the ingredient (C). purpose. Examples thereof include p-hydroxybenzoate 0061 Specific examples of the commercially available esters, chlorobutanol and clesol. product of the ingredient (C) include vitamin B1 nitrate (trade 0071. The binding agent, thickener and adhesive agent are name) (product of Wako Pure Chemical Industries, Ltd.), not particularly limited and may be appropriately selected vitamin B1 hydrochloride (trade name) (product of depending on the intended purpose. Examples thereof AccuStandard Inc.) and thiamine disulfide (trade name) include starch, dextrin, maltitol, cellulose, methyl cellulose, (product of JUNSEI CHEMICAL CO.,LTD.). ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cel 0062. The amount of the ingredient (C) in the above com lulose, hydroxypropyol cellulose, hydroxypropyolmethyl position is not particularly limited and may be appropriately cellulose, carboxymethyl starch, pullulan, Sodium alginate, selected depending on the intended purpose, but is preferably ammonium alginate, propylene glycol alginic acid esters, 0.05% by mass to 10% by mass, more preferably 0.1% by guar gum, locust bean gum, gum Arabic, Xanthane gum, mass to 5% by mass. gelatin, casein, polyvinyl alcohol, polyethylene oxide, poly 0063. The mass ratio ((A):(C)) of the ingredient (A) and ethylene glycol, ethylene/propylene block polymers, sodium the ingredient (C) in the above composition is not particularly polyacrylates and polyvinylpyrrolidone. limited and may be appropriately selected depending on the 0072 The integrating agent is not particularly limited and intended purpose, but is preferably 1:100 to 10,000:1, more may be appropriately selected depending on the intended preferably 1:10 to 1,000:1, particularly preferably 1:1 to 300: purpose. Examples of the integrating agent include water, 1. ethanol, propanol, simple syrup, glucose liquid, starch liquid, 0064. When the mass ratio (A):(C)) falls within the above gelatin liquid, carboxymethyl cellulose, hydroxypropyl cel preferred range, advantageously, more excellent glucose lulose, hydroxypropyl starch, methyl cellulose, ethyl cellu metabolism-improving effects can be obtained. lose, shellac, calcium phosphate, calcium Stearate and poly 0065. The composition of the present invention is not par vinylpyrrolidone. ticularly limited and may be appropriately selected depend 0073. The colorant is not particularly limited and may be ing on the intended purpose so long as it contains: the ingre appropriately selected depending on the intended purpose. dient (A); and at least one of the ingredient (B) and the Examples thereof include titanium oxide and iron oxide. ingredient (C). The composition of the present invention pref 0074 The stabilizer is not particularly limited and may be erably contains at least the ingredient (A) and the ingredient appropriately selected depending on the intended purpose. (B). Particularly preferably, the composition of the present Examples thereof include tragacanth, gum Arabic, gelatin, invention contains all of the ingredient (A), the ingredient (B) sodium pyrosulfite, EDTA, thioglycolic acid and thiolactic and the ingredient (C), since more excellent glucose metabo acid. lism-improving effects can be obtained. (0075. The pH adjuster and the buffer are not particularly 0066. When the above composition contains all of the limited and may be appropriately selected depending on the ingredient (A), the ingredient (B) and the ingredient (C), the intended purpose. Examples thereof include sodium citrate, mass ratio ((B):(C)) of the ingredient (B) and the ingredient Sodium acetate and sodium phosphate. (C) is not particularly limited and may be appropriately 0076. The tonicity agent is not particularly limited and selected depending on the intended purpose, but is preferably may be appropriately selected depending on the intended 1:0.01 to 1:100, more preferably 1:0.1 to 1:10. When the mass purpose. Examples thereof include Sodium chloride and glu ratio ((B):(C)) falls within the above preferred range, advan COSC. tageously, more excellent glucose metabolism-improving 0077. The amount of the other ingredients in the compo effects of the ingredient (A) can be obtained. sition is not particularly limited and may be appropriately lism-improving agent, and method for improving glucose I0089. The amount of the composition in the food, bever metabolism of the present invention. age or pharmaceutical drug is not particularly limited and may be appropriately selected depending on the type of the (Glucose Metabolism-Improving Composition) food or beverage so long as the effects of the present invention 0081. A glucose metabolism-improving composition of are not impaired. Also, the food or beverage may be the the present invention contains at least the composition of the composition itself. present invention; and, if necessary, further contains other ingredients. maceutical drug are not particularly limited and may be 0082. The amount of the above composition in the glucose appropriately selected depending on, for example, the type of metabolism-improving composition is not particularly lim foods or beverages to which the composition is to be incor ited and may be appropriately selected depending on the porated. Examples thereof include Supplemental materials or intended purpose so long as the effects of the present inven additives commonly used for the production of foods, bever tion are not impaired. The glucose metabolism-improving ages or pharmaceutical drugs. composition may be the above composition itself. 0091 Examples of the supplemental materials or additives include glucose, fructose, Sucrose, maltose, Sorbitol, Stevio

(Method for Improving Glucose Metabolism) I0123. The animal species serving as the target of the 0112 A method for improving glucose metabolism of the method for improving glucose metabolism is not particularly present invention includes simultaneously giving (A) Panax limited and may be appropriately selected depending on the notoginseng, and at least one of (B) a Piper longum extract intended purpose. Examples thereof include human, monkey, and (C) vitamin B1, a salt thereof or a derivative thereof. pig, bovine, sheep, goat, dog, cat, mouse, rat and bird, with 0113. The ingredient (A), the ingredient (B) and the ingre human being Suitably used. dient (C) used may be the same as those described for the

A Blood glucose level (mg/dL)=Blood glucose level (0145. From the results of Table 1, it is found that after the before the start of breeding with the mixed feed (mg/dL)-Blood glucose level after the breeding breeding with the mixed feed for 5 days. Examples 1 to 3 with the mixed feed (mg/dL) where the Panax notoginseng (ingredient (A)) was given in combination with at least one of the Piper longum extract (ingredient (B)) and the vitamin B1 nitrate (ingredient (C))

Ex. 1 1 O.083 O.1 375.6 144.4 231.2 Ex. 2 1 O.083 373.8 157.0 216.8 Ex. 3 1 O.1 376.4 201.8 1746 Comp. 1 353.8 287.4 66.4 Ex. 1 Comp. O.1 389.2 345.3 43.9 Ex. 2 Comp. O.83 391.7 3S4.2 37.5 Ex. 3 Comp, 399.4 451.8 -52.4 Ex. 4 US 2014/0050805 A1 Feb. 20, 2014

Examples 4 to 8 and Comparative Examples 5 to 8 notoginseng powder instead of the acid-treated Panax noto 0149 Mixed feeds of Examples 4 to 7 and Comparative ginseng product exhibit significant blood-glucose-level Examples 6 to 8 were prepared by mixing a commercially reducing effects at a significance level of lower than 5% as available high fat diet (trade name: Quick Fat, product of compared with Comparative Example 5 (control) using none CLEA , Inc.) with the acid-treated Panax notoginseng of the ingredients (A), (B) and (C). product produced in Production Example 1 and at least one of 0153. Also, as compared with Comparative Example 6 Piper longum extract (trade name, LONG PEPPER where the acid-treated Panax notoginseng product only was EXTRACT POWDERMF, composition: 10% by mass of a mixed. Examples 4 to 7 exhibit significant blood-glucose hot water extract of Piper longum, 90% by mass of dextrin, level reducing effects at a significance level of lower than 5%. product of MARUZEN PHARMACEUTICALS CO.,LTD.) 0154) In addition, as compared with Example 5 where the and vitamin B1 nitrate (product of Wako Pure Chemical Piper longum extract (ingredient (B)) only was added to the Industries, Ltd.) in respective amounts shown in the following acid-treated Panax notoginseng product (ingredient (A)) and Table 2. The mixed feed of Example 8 was prepared by using Example 6 where the vitamin B1 nitrate (ingredient (C)) only Panax notoginseng powder (product of MATSUURA was added to the acid-treated Panax notoginseng product YAKUGYO CO., LTD.) instead of the acid-treated Panax (ingredient (A)). Example 4 where both the Piper longum notoginseng product of Example 4. The above commercially extract (ingredient (B)) and the vitamin B1 nitrate (ingredient available high fat diet only was used in Comparative Example (C)) were added to the acid-treated Panax notoginseng prod 5. uct (ingredient (A)) exhibits higher blood-glucose-level 0150 Hyperglycemia model mice (KKAy mice (obtained reducing effects and confirms more excellent glucose from CLEA Japan, Inc.), 20 weeks old, 5 mice/group) were metabolism-improving effects. given ad libitum each of the mixed feeds of Examples 4 to 8 and Comparative Examples 5 to 8 to breed them for 5 days. 0155 The composition of the present invention is prefer 0151. The blood glucose levels at 10 a.m. were measured ably used as a drinkable preparation or a solid preparation. in the same manner as in Example 1, before giving the mixed Formulation Examples (2 examples) will next be given. feed to the hyperglycemia model mice (before the start of breeding with the mixed feed) and after giving the mixed feed Formulation Example 1 to the hyperglycemia model mice for 5 days (after the breed ing with the mixed feed). Averages of the measured blood Drinkable Preparation glucose levels are shown in the following Table 2. A signifi cance test was performed using the Dunnett's multiple test. 0156 The following ingredients of a drinkable prepara Also, the A blood glucose levels calculated in the same man tion were mixed with and dissolved in purified water to obtain ner as in Example 1 are also given in the following Table 2. 100 mL of a drinkable preparation (pH-4.5). TABLE 2

Amounts (% by mass) (A) Blood glucose levels (mg/dL)

Acid- Before the treated (B) start of After the A Blood Panax Panax Piper (C) breeding with breeding glucose notoginseng notoginseng longum Vitamin the mixed with the level product powder extract B1 nitrate feed mixed feed (mg/dL)

Ex. 4 1 O.083 O.1 582 246 336 Ex. S 1 O.083 555 276 279 Ex. 6 1 O.1 565 328 237 Ex. 7 7 O.83 O.1 573 251 322 Ex. 8 1 O.83 O.1 553 387 166 Comp. S46 590 -44 Ex. S Comp. 1 550 4O6 144 Ex. 6 Comp. O.083 S49 486 63 Ex. 7 Comp. O.1 551 5O1 50 Ex. 8

0152. From the results of Table 2, it is found that after the Ingredients of Drinkable Preparation breeding with the mixed feed for 5 days. Examples 4 to 7 where the acid-treated Panax notoginseng product (ingredi 0157 Acid-treated Panax notoginseng product of Produc ent (A)) was given in combination with at least one of the tion Example 1 (ingredient (A)): 1,000 mg Piper longum extract (ingredient (B)) and the vitamin B1 LONG PEPPER EXTRACT POWDER MF (composition: nitrate (ingredient (C)) and Example 8 containing the Panax 10% by mass of a hot water extract of Piper longum (ingre US 2014/0050805 A1 Feb. 20, 2014

dient (B)), 90% by mass of dextrin, product of MARUZEN LONG PEPPEREXTRACT POWDERMF (ingredient (B)): PHARMACEUTICALS CO.,LTD.): 1,000 mg 10 mg Vitamin B1 nitrate (product of Wako Pure Chemical Indus Acid-treated Panax notoginseng product of Production tries, Ltd.) (ingredient (C)): 10 mg Example 1 (ingredient (A)): 20 mg Ascorbic acid: 500 mg 0.167 Aspects of the present invention are as follows. 0168 <1> A composition, including: Maltitol: 15,000 mg 0169 (A) Panax notoginseng; and 0170 at least one of (B) a Piper longum extract and (C) Vitamin B6: 10 mg vitamin B1, a salt thereof or a derivative thereof. 0171 <2> The composition according to <1>, wherein the Inositol 50 mg (A) Panax notoginseng is an acid-treated product of the 0158 Anhydrous caffeine: 20 mg Panax notoginseng: Malic acid: 150 mg 0172 <3> The composition according to <1> or <2>. Citric acid: 700 mg wherein the (A) Panax notoginseng contains at least one of Sodium citrate: appropriate amount (pH adjuster) panaxadiol and panaxatriol, and a total amount of the panaxa diol and the panaxatriol is 0.1% by mass to 50% by mass. Glycerin: 60 mg 0173 <4> A food, a beverage or a pharmaceutical drug, including: 0159 Sodium benzoate: 70 mg 0.174 the composition according to any one of <1> to <3>. Perfume: appropriate amount 0.175 <5> A glucose metabolism-improving composition, Formulation Example 2 including: 0176 the composition according to any one of <1> to <3>. Tablet 0177 <6> A glucose metabolism-improving agent, including: 0160 Gelatin (130 g), glycerin (70 g), water (100 g) and ethyl p-hydroxybenzoate (0.5 g) were stirred under heating to 0.178 the composition according to any one of <1> to <3>. obtain a homogeneous gelatin dispersion liquid (L1). 0179 <7> A method for improving glucose metabolism, 0161 Separately, enzymatically decomposed lecithin the method including: (100g), dipotassium glycyrrhizate (0.4 g), vitamin B1 nitrate 0180 simultaneously giving (A) Panax notoginseng, and (product of Wako Pure Chemical Industries, Ltd.) (ingredient at least one of (B) a Piper longum extract and (C) vitamin B1, (C)) (1 g), LONG PEPPEREXTRACT POWDERMF (com a salt thereof or a derivative thereof. position: 10% by mass of a hot water extract of Piper longum (ingredient (B)), 90% by mass of dextrin, product of INDUSTRIAL APPLICABILITY MARUZEN PHARMACEUTICALS CO.,LTD.) (10 g) and 0181. The composition of the present invention, the food, the acid-treated Panax notoginseng product of Production beverage, pharmaceutical drug, glucose metabolism-improv Example 1 (ingredient (A)) (20g) were dispersed in wheat ing composition, and glucose metabolism-improving agent, germ oil (200 g) using HOMOMIXER to prepare wheat germ each of which contains the composition, and the method for oil liquid (L2) in the form of homogeneous solution. improving glucose metabolism have excellent glucose 0162 The gelatin dispersion liquid (L1) was extruded into metabolism-improving effects, have high safety, and are a 12 mm-diameter aluminum mold for capsule, to obtain a capable of being conveniently used, and thus can Suitably be gelatin capsule. used for treatment or prevention of abnormal glucose metabo 0163 Next, the wheat germ oil liquid (L2) was extruded lism. with a nozzle to be injected and charged into the gelatin 1. A composition, comprising: capsule, followed by cooling and drying, to thereby obtain a (A) Panax notoginseng; and Solid preparation having a gel outer layer of gelatin charged at least one of (B) a Piper longum extract and (C) vitamin with the wheat germ oil liquid (L2) in the form of liquid B1, a salt thereof or a derivative thereof. (tablet oral drug:gel composition). 2. The composition according to claim 1, wherein the (A) 0164. The composition per one piece of the above solid Panax notoginseng is an acid-treated product of the Panax preparation is given below. notoginSeng. 3. The composition according to claim 1, wherein the (A) Solid Preparation/1 Piece Panax notoginseng contains at least one of panaxadiol and panaxatriol, and a total amount of the panaxadiol and the —Outer Layer— panaxatriol is 0.1% by mass to 50% by mass. 4. The composition according to claim 1, wherein the com Gelatin: 130 mg position is used in a food, a beverage or a pharmaceutical Glycerin: 70 mg drug. 5. The composition according to claim 1, wherein the com 0.165 Ethyl p-hydroxybenzoate: 0.5 mg position is used in a glucose metabolism-improving compo sition. —Inner Layer— 6. A glucose metabolism-improving agent, comprising: 0166 Enzymatically decomposed lecithin: 50 mg a composition which comprises: Dipotassium glycyrrhizate: 0.4 mg (A) Panax notoginseng; and Wheat germ oil: 100 mg at least one of (B) a Piper longum extract and (C) vitamin Vitamin B1 nitrate (ingredient (C)): 1.0 mg B1, a salt thereof or a derivative thereof. US 2014/0050805 A1 Feb. 20, 2014 11

7. A method for improving glucose metabolism, the method comprising: simultaneously giving (A) Panax notoginseng, and at least one of (B) a Piper longum extract and (C) vitamin B1, a salt thereof or a derivative thereof.

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