JP2015117213A - Solid form composition - Google Patents
Solid form composition Download PDFInfo
- Publication number
- JP2015117213A JP2015117213A JP2013262439A JP2013262439A JP2015117213A JP 2015117213 A JP2015117213 A JP 2015117213A JP 2013262439 A JP2013262439 A JP 2013262439A JP 2013262439 A JP2013262439 A JP 2013262439A JP 2015117213 A JP2015117213 A JP 2015117213A
- Authority
- JP
- Japan
- Prior art keywords
- hesperidin
- carbonate
- solid composition
- component
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title abstract description 14
- 239000007787 solid Substances 0.000 title abstract description 5
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims abstract description 84
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims abstract description 71
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims abstract description 69
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims abstract description 69
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims abstract description 69
- 229940025878 hesperidin Drugs 0.000 claims abstract description 69
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims abstract description 69
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims abstract description 69
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 25
- 150000007524 organic acids Chemical class 0.000 claims abstract description 25
- 239000008247 solid mixture Substances 0.000 claims description 30
- GUMSHIGGVOJLBP-SLRPQMTOSA-N methyl hesperidin Chemical compound C1=C(OC)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 GUMSHIGGVOJLBP-SLRPQMTOSA-N 0.000 claims description 18
- 235000000346 sugar Nutrition 0.000 claims description 17
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- 239000000796 flavoring agent Substances 0.000 abstract description 11
- 235000019634 flavors Nutrition 0.000 abstract description 10
- 206010013911 Dysgeusia Diseases 0.000 abstract description 7
- 239000003826 tablet Substances 0.000 description 18
- 235000019658 bitter taste Nutrition 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 235000019606 astringent taste Nutrition 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 8
- 238000005469 granulation Methods 0.000 description 8
- 230000003179 granulation Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 235000001727 glucose Nutrition 0.000 description 6
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- 238000002360 preparation method Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 150000001788 chalcone derivatives Chemical class 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- 229960004106 citric acid Drugs 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 230000001766 physiological effect Effects 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- FDHNLHLOJLLXDH-JIYHLSBYSA-N (e)-3-(3-hydroxy-4-methoxyphenyl)-1-[2-hydroxy-6-methoxy-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-[[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxyphenyl]prop-2-en-1-one Chemical compound C1=C(O)C(OC)=CC=C1\C=C\C(=O)C(C(=C1)OC)=C(O)C=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)O1 FDHNLHLOJLLXDH-JIYHLSBYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007910 chewable tablet Substances 0.000 description 3
- -1 for example Chemical compound 0.000 description 3
- 229930182470 glycoside Natural products 0.000 description 3
- 150000002338 glycosides Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical group C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 description 3
- 229940076640 hesperidin methylchalcone Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000001630 malic acid Substances 0.000 description 3
- 235000011090 malic acid Nutrition 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 235000019643 salty taste Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZONYXWQDUYMKFB-UHFFFAOYSA-N SJ000286395 Chemical class O1C2=CC=CC=C2C(=O)CC1C1=CC=CC=C1 ZONYXWQDUYMKFB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、ヘスペリジンを含有する固形状組成物に関する。 The present invention relates to a solid composition containing hesperidin.
フラボノイドの一種であるヘスペリジンは、ビタミンPとも呼ばれ、柑橘類の皮等に多く含まれることが知られている物質である。ヘスペリジンは、毛細血管の強化、出血予防、血圧調整等の様々な生理作用を有することが報告され、生体への利用が期待されている。
ヘスペリジンの生理機能をより効果的に発現させるには、ヘスペリジンの摂取量を増やすことが大切であり、また、それを簡便に達成可能とする手段として飲料の形態とすることが提案されている(例えば、特許文献1)。
Hesperidin, a kind of flavonoid, is also called vitamin P, and is a substance known to be contained in a large amount in citrus peel and the like. Hesperidin has been reported to have various physiological effects such as strengthening of capillaries, bleeding prevention, blood pressure regulation and the like, and is expected to be used for living bodies.
In order to more effectively express the physiological function of hesperidin, it is important to increase the intake of hesperidin, and it has been proposed to make it in the form of a beverage as a means for easily achieving it ( For example, Patent Document 1).
一方、錠剤や散剤等の固形状組成物は、携帯性や保存性に優れ、1回当たり少量で、簡便且つ手軽に摂取できる経口摂取に適した形態である。とりわけ、炭酸塩と有機酸を配合した発泡剤は、摂取すると口内において唾液との接触により発泡し、独特の清涼感が得られるため好適な形態である。
また、発泡剤は、経口用成分の吸収速度を高める目的で用いられることがあり、例えば、濃縮緑茶植物抽出物と炭酸塩と酸を配合し、身体による吸収を迅速にしてバイオアベイラビリティーを向上させた発泡性組成物を形成する固体水溶性製剤が知られている(特許文献2)。
On the other hand, solid compositions such as tablets and powders are excellent in portability and storage stability, and are in a form suitable for oral intake that can be easily and easily ingested in a small amount per time. In particular, a foaming agent containing a carbonate and an organic acid is a suitable form since it foams by contact with saliva in the mouth when ingested, and a unique refreshing feeling can be obtained.
In addition, foaming agents may be used for the purpose of increasing the absorption rate of oral components. For example, a concentrated green tea plant extract, carbonate, and acid are blended to accelerate absorption by the body and improve bioavailability. A solid water-soluble preparation for forming a foamable composition is known (Patent Document 2).
しかしながら、本発明者らが、ヘスペリジンを含有する固形状組成物を開発すべく検討したところ、ヘスペリジンを固形状組成物中に配合し、それを高濃度化するに従いヘスペリジン特有の苦味が感じられるだけでなく、苦味とは異質の収斂感が感じられ、後に収斂味が残存することが判明した。
したがって、本発明の課題は、後に残る収斂味、苦味が抑えられ、風味の良好なヘスペリジンを含有する固形状組成物を提供することにある。
However, when the present inventors examined to develop a solid composition containing hesperidin, hesperidin was blended into the solid composition, and only the bitterness peculiar to hesperidin was felt as the concentration was increased. In addition, it was found that an astringent feeling different from the bitter taste was felt and the astringent taste remained later.
Accordingly, an object of the present invention is to provide a solid composition containing hesperidin having a good flavor and suppressing astringency and bitterness remaining thereafter.
本発明者らは、上記課題を解決するため鋭意検討を重ねた結果、ヘスペリジンに所定量の炭酸塩と、更に有機酸を所定の割合で組み合わせ、摂取時に炭酸ガスを発生させることにより、ヘスペリジン特有の後に残る収斂味と苦味が低減されて、風味の良好な固形状組成物とすることができることを見出した。
すなわち、本発明は、次の成分(A)、(B)及び(C):
(A)ヘスペリジン及び/又はヘスペリジン誘導体、
(B)炭酸塩、
(C)有機酸、
を含有し、成分(A)と成分(B)の含有質量比[(B)/(A)]が0.25以上であり、且つ成分(C)と成分(B)の当量比[(C)の当量/(B)の当量]が0.8〜3である固形状組成物を提供するものである。
As a result of intensive studies to solve the above-mentioned problems, the present inventors combined hesperidin with a predetermined amount of carbonate and further an organic acid in a predetermined ratio to generate carbon dioxide gas when ingested, thereby producing hesperidin-specific It has been found that the astringent taste and bitterness remaining after the reduction can be reduced to obtain a solid composition having a good flavor.
That is, the present invention includes the following components (A), (B) and (C):
(A) hesperidin and / or hesperidin derivative,
(B) carbonate,
(C) an organic acid,
The mass ratio of component (A) to component (B) [(B) / (A)] is 0.25 or more, and the equivalent ratio of component (C) to component (B) [(C ) Equivalent / (B) equivalent] is provided in a solid composition of 0.8-3.
本発明によれば、ヘスペリジン特有の後に残る収斂味と苦味が抑えられ、また、炭酸塩由来の塩味や有機酸由来の酸味も少ない、風味の良好なヘスペリジンを含有する固形状組成物を提供することができる。 According to the present invention, there is provided a solid composition containing hesperidin having a good flavor, which can suppress the astringent taste and bitterness remaining after hesperidin, and has little salty taste derived from carbonate or organic acid. be able to.
本発明で用いる(A)ヘスペリジンは、ヘスペレチン(5,7,3'−トリヒドロキシ−4'−メトキシフラバノン)の7位の水酸基にルチノース(L−ラムノシル−(α1→6)−D−グルコース)がβ結合した化合物である。
本発明のヘスペリジン誘導体は、ヘスペリジンに糖が結合した配糖体、ヘスペリジンのメチル化物を用いることができる。
(A) Hesperidin used in the present invention is rutinose (L-rhamnosyl- (α1 → 6) -D-glucose) at the hydroxyl group at the 7-position of hesperetin (5,7,3′-trihydroxy-4′-methoxyflavanone). Is a β-bonded compound.
As the hesperidin derivative of the present invention, a glycoside in which a sugar is bonded to hesperidin, or a methylated product of hesperidin can be used.
ヘスペリジンに糖が結合した配糖体としては、ヘスペリジンに更に1個〜10個の糖が結合した化合物が挙げられる。糖としては、グルコース、マルトース、フルクトース、ラムノース、ラクトース等が挙げられる。なかでも、溶解性及び可溶化力の点から、ヘスペリジンに1個〜10個のグルコースが結合したグルコシルヘスペリジンが好ましく、更にグルコース1個が結合したモノグルコシルヘスペリジンが好ましい。また、グルコースの付加数は分布を持っていてもよく、ヘスペリジン1モルに対するグルコースの平均付加モル数は1〜10が好ましい。なお、ヘスペリジン自身も、上記のとおり、ヘスペレチンをアグリコンとし、これに糖が結合した配糖体である。本発明においてはこれと区別するため、ヘスペリジンに更に糖が結合したものをヘスペリジン糖付加物と表記する。 Examples of glycosides in which sugars are bonded to hesperidin include compounds in which 1 to 10 sugars are further bonded to hesperidin. Examples of the sugar include glucose, maltose, fructose, rhamnose, lactose and the like. Among these, from the viewpoint of solubility and solubilizing power, glucosyl hesperidin in which 1 to 10 glucoses are bonded to hesperidin is preferable, and monoglucosyl hesperidin in which 1 glucose is further bonded is preferable. Moreover, the addition number of glucose may have distribution, and the average addition mole number of glucose with respect to 1 mol of hesperidins is 1-10. As described above, hesperidin itself is a glycoside in which hesperetin is used as an aglycone and a sugar is bound thereto. In the present invention, in order to distinguish from this, a substance in which a sugar is further bonded to hesperidin is referred to as a hesperidin sugar adduct.
これらのヘスペリジン及びヘスペリジン糖付加物は、化学合成や酵素反応を利用して公知の方法により工業的に製造することができる。また、ヘスペリジンについては、これを含有する天然物、好ましくは植物から抽出することによって得ることもできる。これらの物質はまた、試薬等として製造販売されている。市販されているヘスペリジンの例としては、浜理薬品工業(株)のヘスペリジン「ハマリ」が挙げられる。市販されているヘスペリジン糖付加物の例としては、(株)林原生物科学研究所の「林原ヘスペリジンS」が挙げられる。 These hesperidins and hesperidin sugar adducts can be industrially produced by a known method using chemical synthesis or enzymatic reaction. Hesperidin can also be obtained by extraction from natural products containing it, preferably from plants. These substances are also manufactured and sold as reagents and the like. As an example of commercially available hesperidin, hesperidin “Hamari” manufactured by Hamari Pharmaceutical Co., Ltd. may be mentioned. Examples of commercially available hesperidin sugar adducts include “Hayashibara Hesperidin S” from Hayashibara Bioscience Institute.
メチルヘスペリジンには、主に、カルコン型化合物(1)及びフラバノン型化合物(2)が含まれることが知られており、その構成成分として、例えば以下に示す構造のものが挙げられる。 Methyl hesperidin is known to mainly contain chalcone type compounds (1) and flavanone type compounds (2), and examples of the constituents include those having the structures shown below.
(式中、Rは水素原子又はメチル基を表す。)
ここで、医薬品添加物及び食品添加物としてのメチルヘスペリジンは、主に、化合物(3)及び(4)の混合物として取り扱われている。
(In the formula, R represents a hydrogen atom or a methyl group.)
Here, methyl hesperidin as a pharmaceutical additive and a food additive is mainly handled as a mixture of the compounds (3) and (4).
(式中、Glは、グルコース残基、Rhは、ラムノース残基を表す。また、Gl−2は、グルコース残基の2位((3−1)の場合、3位も含む)、Rh−2は、ラムノース残基の2位を表す。)
また、化粧品原料としてのヘスペリジンメチルカルコンは、(5)で示される化合物として取り扱われている。なお、カルコン型化合物を多く含む組成の場合、ヘスペリジンメチルカルコンとも呼ばれる。
(In the formula, Gl represents a glucose residue, Rh represents a rhamnose residue, and Gl-2 represents the 2-position of the glucose residue (including 3-position in the case of (3-1)), Rh- 2 represents position 2 of the rhamnose residue.)
Hesperidin methyl chalcone as a cosmetic raw material is handled as a compound represented by (5). In the case of a composition containing a large amount of chalcone type compound, it is also called hesperidin methyl chalcone.
(式中、Rは水素原子又はメチル基を表す。)
本発明で用いるメチルヘスペリジンは、上記で示したカルコン型化合物(1)とフラバノン型化合物(2)の両方を含むものでもよいし、また、それぞれの片方のみを含むものでもよい。
本発明において、より好適なメチルヘスペリジンとしては、化合物(3)と化合物(4)の混合物が挙げられる。
メチルヘスペリジンは、公知の方法、例えば、ヘスペリジンを水酸化ナトリウム水溶液に溶かし、そのアルカリ溶液に対応量のジメチル硫酸を作用させ、反応液を硫酸で中和し、n−ブチルアルコールで抽出し、溶媒を留去したのち、イソプロピルアルコールで再結晶することにより製造できるが(崎浴、日本化學雑誌、79、733−6(1958))、その製造法はこれに限るものではない。
メチルヘスペリジンとして市販のメチルヘスペリジン含有製剤を使用してもよく、例えば、「メチルヘスペリジン」(アルプス薬品工業(株))、「ヘスペリジンメチルカルコン」(Sigma社)、「メチルヘスペリジン」(浜理薬品工業(株))が挙げられる。
(In the formula, R represents a hydrogen atom or a methyl group.)
The methyl hesperidin used in the present invention may contain both the chalcone type compound (1) and the flavanone type compound (2) shown above, or may contain only one of them.
In the present invention, more preferred methyl hesperidin includes a mixture of compound (3) and compound (4).
Methyl hesperidin is a known method, for example, hesperidin is dissolved in an aqueous sodium hydroxide solution, a corresponding amount of dimethyl sulfate is allowed to act on the alkaline solution, the reaction solution is neutralized with sulfuric acid, and extracted with n-butyl alcohol. It can be produced by distilling off and then recrystallizing with isopropyl alcohol (Saki Bath, Nippon Kagaku Kagaku, 79, 733-6 (1958)), but the production method is not limited to this.
Commercially available methyl hesperidin-containing preparations may be used as methyl hesperidin, for example, “methyl hesperidin” (Alps Yakuhin Kogyo Co., Ltd.), “hesperidin methyl chalcone” (Sigma), “methyl hesperidin” (Hamari Yakuhin Kogyo) Co., Ltd.).
本発明の固形状組成物中、(A)ヘスペリジン及び/又はヘスペリジン誘導体の含有量は、4〜60質量%(以下、「%」とする)が好ましく、更に9〜60%、更に10〜55%、更に15〜50%、更に15〜40%であることが風味、有効量を摂取するに必要な錠剤数の点から好ましい。
なお、本明細書において「成分(A)の含有量」は、ヘスペリジンとヘスペリジン誘導体の合計量に基づいて定義され、また、ヘスペリジン誘導体がヘスペリジン糖付加物の場合はヘスペリジン糖付加物の含有量とし、また、メチルヘスペリジンの場合はメチルヘスペリジンの含有量とする。
In the solid composition of the present invention, the content of (A) hesperidin and / or hesperidin derivative is preferably 4 to 60% by mass (hereinafter referred to as “%”), more preferably 9 to 60%, and further 10 to 55. %, Further 15 to 50%, and further 15 to 40% is preferable from the viewpoint of the number of tablets necessary for ingesting the flavor and effective amount.
In the present specification, “content of component (A)” is defined based on the total amount of hesperidin and hesperidin derivative, and when the hesperidin derivative is a hesperidin sugar adduct, the content of hesperidin sugar adduct is defined as the content of hesperidin sugar adduct. In the case of methyl hesperidin, the content is methyl hesperidin.
本発明で用いる(B)炭酸塩としては、例えば、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸水素カリウム、炭酸カルシウム、炭酸マグネシウム、セスキ炭酸ナトリウム等が挙げられ、これらは単独で又は2種以上を組み合わせて用いることができる。 Examples of the carbonate (B) used in the present invention include sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, calcium carbonate, magnesium carbonate, sodium sesquicarbonate, and the like. These may be used alone or in combination of two or more. Can be used in combination.
本発明の固形状組成物中、(B)炭酸塩の含有量は、3〜40%であるのが好ましく、更に5〜35%、更に10〜20%であることが、風味、物性の点、(A)成分を多く含有させ生理効果を高める点から好ましい。 In the solid composition of the present invention, the content of (B) carbonate is preferably 3 to 40%, more preferably 5 to 35%, and further 10 to 20%, in terms of flavor and physical properties. (A) It is preferable from the point which contains many components and raises a physiological effect.
本発明の固形状組成物においては、(A)ヘスペリジン及び/又はヘスペリジン誘導体と(B)炭酸塩の含有質量比[(B)/(A)]を0.25以上とする。(A)ヘスペリジン及び/又はヘスペリジン誘導体と(B)炭酸塩の含有質量比[(B)/(A)]は、収斂味、苦味抑制の点から、更に0.27以上、更に0.3以上、更に0.35以上、更に0.4以上、更に0.5以上、更に0.7以上が好ましい。また、(A)ヘスペリジン及び/又はヘスペリジン誘導体と(B)炭酸塩の含有質量比[(B)/(A)]は、(A)成分を多く含有させ生理効果を高める点から、7以下が好ましく、更に6以下、更に5以下、更に4以下、更に3以下、更に2以下が好ましい。 In the solid composition of the present invention, the mass ratio [(B) / (A)] of (A) hesperidin and / or hesperidin derivative and (B) carbonate is set to 0.25 or more. (A) Hesperidin and / or hesperidin derivative and (B) carbonate content mass ratio [(B) / (A)] is 0.27 or more, more 0.3 or more from the viewpoint of astringency and bitterness suppression. Further, 0.35 or more, further 0.4 or more, further 0.5 or more, and further 0.7 or more are preferable. Further, the mass ratio [(B) / (A)] of (A) hesperidin and / or hesperidin derivative and (B) carbonate is 7 or less from the viewpoint of increasing the physiological effect by containing a large amount of component (A). More preferably, it is 6 or less, further 5 or less, further 4 or less, further 3 or less, and further 2 or less.
また、本発明で用いる(C)有機酸としては、可食性の酸を使用することができる。例えば、クエン酸、コハク酸、アスコルビン酸、酢酸、グルコン酸、リンゴ酸、酒石酸、フマル酸、アジピン酸等の有機酸が挙げられ、これらは単独で又は2種以上を組み合わせて用いることができる。なかでも、有機酸の味の点、発生する泡の食感が良好な点から、クエン酸又はリンゴ酸が好ましく、更にクエン酸が好ましい。 In addition, as the organic acid (C) used in the present invention, an edible acid can be used. Examples thereof include organic acids such as citric acid, succinic acid, ascorbic acid, acetic acid, gluconic acid, malic acid, tartaric acid, fumaric acid and adipic acid, and these can be used alone or in combination of two or more. Of these, citric acid or malic acid is preferable, and citric acid is more preferable because of the taste of the organic acid and the texture of the foam generated.
本発明の固形状組成物中、(C)有機酸の含有量は、5.5〜50%、更に8〜30%、更に10〜25%であることが風味、物性の点、(A)成分を多く含有させ生理効果を高める点から好ましい。 In the solid composition of the present invention, the content of (C) the organic acid is 5.5 to 50%, more preferably 8 to 30%, and further 10 to 25%. This is preferable from the viewpoint of increasing the physiological effect by containing many components.
本発明の固形状組成物においては、(C)有機酸と(B)炭酸塩の当量比[(C)の当量/(B)の当量]を、0.8〜3の範囲とする。炭酸塩由来の塩味や有機酸の酸味が突出せず、風味のバランスが良好となる。(C)有機酸と(B)炭酸塩の当量比は、上記と同様の点から、更に0.9〜3.0、更に0.9〜2.7、更に0.95〜2.0、更に0.95〜1.8が好ましい。
なお、本発明において、前記「当量比」とは、固形状組成物に含まれる(C)有機酸の当量を(B)炭酸塩の当量で除した値である。
In the solid composition of the present invention, the equivalent ratio of (C) organic acid and (B) carbonate [equivalent of (C) / equivalent of (B)] is in the range of 0.8 to 3. The salty taste derived from carbonates and the sourness of organic acids do not protrude, and the flavor balance is good. The equivalent ratio of (C) organic acid to (B) carbonate is 0.9 to 3.0, 0.9 to 2.7, 0.95 to 2.0, Furthermore, 0.95-1.8 is preferable.
In the present invention, the “equivalent ratio” is a value obtained by dividing the equivalent of (C) the organic acid contained in the solid composition by the equivalent of (B) carbonate.
また、本発明の固形状組成物においては、固形状組成物中の(A)ヘスペリジンの含有量に対する(B)炭酸塩と(C)有機酸の合計含有量の比(質量比)[(B)+(C)/(A)]を、0.3〜10、更に0.5〜5、更に0.7〜3、更に0.8〜2の範囲とするのが風味、錠数を少なくし、効率的にヘスペリジンを摂取する1錠当たりのヘスペリジン含有量の点から好ましい。 Further, in the solid composition of the present invention, the ratio (mass ratio) of the total content of (B) carbonate and (C) organic acid to the content of (A) hesperidin in the solid composition [(B ) + (C) / (A)] is in the range of 0.3 to 10, more preferably 0.5 to 5, more preferably 0.7 to 3, and more preferably 0.8 to 2, to reduce the flavor and the number of tablets. From the viewpoint of the content of hesperidin per tablet for efficiently ingesting hesperidin.
本発明の固形状組成物には、上記成分の他に、本発明の効果を損なわない範囲において、ミネラル(例えば、カルシウム、マグネシウム、鉄、亜鉛、クロム、セレン、マンガン、モリブデン、銅、ヨウ素、リン、カリウム、ナトリウム)、ビタミン(例えば、ビタミンA、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12、ビタミンC、ビタミンE、葉酸及びそれらの塩、又はそれらのエステル)、甘味料(例えば、フルクトース、グルコース、ガラクトース、キシロース、タガトース等の単糖、例えば、ショ糖、乳糖、麦芽糖、トレハロース、イソマルトオリゴ糖、ガラクトオリゴ糖、フラクトオリゴ糖、乳果オリゴ糖、大豆オリゴ糖、イソマルツロース、カップリングシュガー等の少糖、炭素数6〜12の糖アルコール、サッカリン、スクラロース、アセスルファムカリウム等の合成甘味料)、前記「(C)有機酸」以外の酸味料、香料、着色料、保存料等が適宜配合されていてもよい。 In the solid composition of the present invention, in addition to the above components, minerals (for example, calcium, magnesium, iron, zinc, chromium, selenium, manganese, molybdenum, copper, iodine, Phosphorus, potassium, sodium), vitamins (eg, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin E, folic acid and their salts, or esters thereof), sweeteners (eg, fructose) Monosaccharides such as glucose, galactose, xylose, tagatose, for example, sucrose, lactose, maltose, trehalose, isomaltoligosaccharide, galactooligosaccharide, fructooligosaccharide, whey oligosaccharide, soybean oligosaccharide, isomaltulose, coupling sugar Such as oligosaccharides, sugar alcohols having 6 to 12 carbon atoms, Karin, sucralose, synthetic sweeteners such as acesulfame potassium), the "(C) an organic acid" other than the acidulant, flavoring, coloring, preservatives, etc. may be appropriately blended.
本発明の固形状組成物は、口内又は水の存在下で炭酸ガスを発生するものである。その形態としては、例えば、室温(15〜25℃)で固形状のものであれば特に限定されないが、例えば、カプセル剤、顆粒剤、散剤、錠剤、丸剤等が挙げられる。なかでも、1回あたり少量で摂取可能な点、摂取が簡便な点から、発泡錠である錠剤、散剤が好ましく、チュアブル錠であることが更に好ましい。
このような剤型の組成物を調製するには、必要に応じて、乳糖、デンプン類、結晶セルロース、蔗糖、マンニトール、軽質無水ケイ酸、リン酸水素カルシウム等の賦形剤;ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、ゼラチン、アルファー化デンプン、ポリビニルピロリドン、ポリビニルアルコール、プルラン、メチルセルロース、硬化油等の結合剤;カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、クロスポピドン、トウモロコシデンプン、低置換度ヒドロキシプロピルセルロース等の崩壊剤;ステアリン酸カルシウム、ステアリン酸マグネシウム、ショ糖脂肪酸エステル、フマル酸ステアリルナトリウム、タルク、二酸化ケイ素等の滑沢剤;ステビア、アスパルテーム等の嬌味剤;香料、増量剤、界面活性剤、分散剤、緩衝剤、保存剤、被膜剤、希釈剤等を適宜組み合わせて用いることができる。
The solid composition of the present invention generates carbon dioxide in the mouth or in the presence of water. The form is not particularly limited as long as it is solid at room temperature (15 to 25 ° C.), and examples thereof include capsules, granules, powders, tablets, and pills. Among these, tablets and powders that are effervescent tablets are preferable, and chewable tablets are more preferable because they can be taken in a small amount per time and are easy to ingest.
In order to prepare a composition of such a dosage form, if necessary, excipients such as lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, calcium hydrogen phosphate; hydroxypropyl methylcellulose, Binding agents such as hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, methylcellulose, hydrogenated oil; carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, low-substituted hydroxypropylcellulose Disintegrating agents such as calcium stearate, magnesium stearate, sucrose fatty acid ester, sodium stearyl fumarate, talc, silicon dioxide, etc .; flavoring agents such as stevia, aspartame; Fee, bulking agents, surfactants, dispersants, buffers, preservatives, coating agents, may be combined as appropriate diluents and the like.
本発明の固形状組成物は、特に制限はなく常法に従い製造される。例えば、(A)ヘスペリジン及び/又はヘスペリジン誘導体、(B)炭酸塩、(C)有機酸及び必要に応じて添加される添加剤の混合物を調製後、圧縮成形することによって製造することができる。
例えば、散剤を製造する場合、(A)ヘスペリジン及び/又はヘスペリジン誘導体、(B)炭酸塩、(C)有機酸及び必要に応じて添加される添加剤の混合物をそのまま用いてもよいし、混合物を粉砕して用いてもよい。散剤は、18号(850μm)ふるいを全量通過することが好ましく、300号(500μm)ふるいに残留するものが全量の5%以下であることがより好ましい。
顆粒剤は、(A)ヘスペリジン及び/又はヘスペリジン誘導体、(B)炭酸塩、(C)有機酸及び必要に応じて添加される添加剤の混合物を乾式造粒法、湿式造粒法等を用いて造粒することにより得ることができる。
錠剤を製造する場合は、原料粉末を直接圧縮して成形(直接粉末圧縮法)しても、乾式造粒法、湿式造粒法等を用いて造粒してから圧縮して成形(顆粒圧縮法)しても良い。なかでも、工程の簡便性の点から、直接粉末圧縮法を用いて錠剤とするのが好ましい。
直接圧縮して成形して錠剤を製造する場合、打錠成形機としてはロータリー式打錠機や単発式打錠機等通常使用されるものを用いることができる。
また、造粒法より造粒してから錠剤とする場合、円筒造粒機、球形整粒機、ペレッター等を使用する押し出し造粒法、スピードミル、パワーミル等を使用する破砕造粒法、転動造粒法、攪拌造粒法、流動層造粒法等により造粒物を製造し、乾燥・整粒した後、得られた造粒物を前記打錠成形機で圧縮して錠剤を形成できる。造粒物の平均粒子径は、45μm〜850μmとするのが好ましく、100μm〜500μmとするのが更に好ましい。
錠剤の形状としては、円形錠もしくは楕円形、長円形、四角形等の面形を有する各種異形錠であってもよい。
また、打錠時の圧縮成型圧は、成型物の硬度維持、崩壊性等の点から、例えば100〜4000kg/cm2である。
The solid composition of the present invention is produced according to a conventional method without any particular limitation. For example, it can be produced by preparing a mixture of (A) hesperidin and / or a hesperidin derivative, (B) carbonate, (C) an organic acid and additives to be added as necessary, and then compression-molding the mixture.
For example, in the case of producing a powder, a mixture of (A) hesperidin and / or hesperidin derivative, (B) carbonate, (C) organic acid and additives added as necessary may be used as it is. May be used after being crushed. The powder preferably passes through the entire size of No. 18 (850 μm) sieve, and the amount remaining on the No. 300 (500 μm) sieve is more preferably 5% or less of the total amount.
For the granule, a dry granulation method, a wet granulation method, or the like is used by mixing a mixture of (A) hesperidin and / or hesperidin derivative, (B) carbonate, (C) organic acid and additives added as necessary. And can be obtained by granulation.
When manufacturing tablets, the raw material powder can be directly compressed and molded (direct powder compression method), or granulated using dry granulation method, wet granulation method, etc. and then compressed (granule compression) Act). Especially, it is preferable to use a direct powder compression method to make a tablet from the point of simplicity of the process.
When a tablet is produced by direct compression and molding, a conventional tableting machine such as a rotary tableting machine or a single-shot tableting machine can be used.
In addition, when a tablet is formed after granulation by a granulation method, an extrusion granulation method using a cylindrical granulator, a spherical granulator, a pelleter, etc., a crushing granulation method using a speed mill, a power mill, etc. A granulated product is produced by dynamic granulation method, stirring granulation method, fluidized bed granulation method, etc., dried and sized, and then the obtained granulated product is compressed by the tableting machine to form tablets. it can. The average particle diameter of the granulated product is preferably 45 μm to 850 μm, and more preferably 100 μm to 500 μm.
The shape of the tablet may be a round tablet or various deformed tablets having a surface shape such as an oval, an oval, or a square.
Moreover, the compression molding pressure at the time of tableting is 100-4000 kg / cm < 2 > from points, such as hardness maintenance of a molding, disintegration, etc., for example.
また、本発明の錠剤の1錠当りの重量は、0.1g以上とするのが簡便性及び有効性の点で好ましい。 Further, the weight per tablet of the tablet of the present invention is preferably 0.1 g or more from the viewpoint of simplicity and effectiveness.
[原料]
ヘスペリジン製剤:ヘスペリジン「ハマリ」、浜理薬品工業(株)製、ヘスペリジン含有量92%
グルコシルヘスペリジン製剤:林原ヘスペリジンS、(株)林原生物化学研究所製、ヘスペリジン含有量17%、モノグルコシルヘスペリジン含有量74%
メチルヘスペリジン製剤:メチルヘスペリジン、アルプス薬品工業(株)製、メチルヘスペリジン含有量100%
炭酸水素ナトリウム:炭酸水素ナトリウム、和光純薬(株)
クエン酸:無水クエン酸MS、扶桑化学工業(株)
リンゴ酸:フソウS、扶桑化学工業(株)
デキストリン:デキストリンM−SPD、昭和産業(株)
ステアリン酸カルシウム:オーラブライトCA−65、日油(株)
[material]
Hesperidin preparation: Hesperidin "Hamari", manufactured by Hamari Pharmaceutical Co., Ltd., Hesperidin content 92%
Glucosyl hesperidin preparation: Hayashibara Hesperidin S, manufactured by Hayashibara Biochemical Laboratory, hesperidin content 17%, monoglucosyl hesperidin content 74%
Methyl hesperidin preparation: methyl hesperidin, manufactured by Alps Pharmaceutical Co., Ltd., methyl hesperidin content 100%
Sodium bicarbonate: Sodium bicarbonate, Wako Pure Chemical Industries, Ltd.
Citric acid: anhydrous citric acid MS, Fuso Chemical Industry Co., Ltd.
Malic acid: Fuso S, Fuso Chemical Industry Co., Ltd.
Dextrin: Dextrin M-SPD, Showa Sangyo Co., Ltd.
Calcium stearate: Orlabrite CA-65, NOF Corporation
[ヘスペリジン、メチルヘスペリジン及びヘスペリジン糖付加物の分析]
ヘスペリジン、メチルヘスペリジン及びヘスペリジン糖付加物の定量は、日立製作所製高速液体クロマトグラフを用い、インタクト社製カラムCadenza CD−C18 (4.6mmφ×150mm、3μm)を装着し、カラム温度40℃でグラジエント法により行った。移動相A液は0.05mol/L酢酸水溶液、B液はアセトニトリルとし、1.0mL/分で送液した。グラジエント条件は以下のとおりである。
時間(分) A液(%) B液(%)
0 85 15
20 80 20
35 10 90
50 10 90
50.1 85 15
60 85 15
試料注入量は10μL、検出はメチルヘスペリジンは波長360nm、ヘスペリジンとヘスペリジン糖付加物は波長283nmの吸光度により定量した。
[Analysis of hesperidin, methyl hesperidin and hesperidin sugar adducts]
Hesperidin, methyl hesperidin, and hesperidin sugar adducts were quantified using a Hitachi high-performance liquid chromatograph, equipped with an intact Cadenza CD-C18 (4.6 mmφ × 150 mm, 3 μm) gradient at a column temperature of 40 ° C. Done by law. The mobile phase A solution was 0.05 mol / L acetic acid aqueous solution, the B solution was acetonitrile, and the solution was fed at 1.0 mL / min. The gradient conditions are as follows.
Time (min) A liquid (%) B liquid (%)
0 85 15
20 80 20
35 10 90
50 10 90
50.1 85 15
60 85 15
The sample injection amount was 10 μL, detection was methyl hesperidin with a wavelength of 360 nm, and hesperidin and hesperidin sugar adduct were quantified with absorbance at a wavelength of 283 nm.
[炭酸塩の分析]
固形状組成物中の炭酸塩の含有量の分析方法は以下の通りである。
固形状組成物を0.1〜0.2g採取し、水10mLと50%りん酸2mLを加え密栓した。10分間超音波処理を行った後、1時間放置しヘッドスペースガスをガスクロマトグラフに供してCO2量を求め、発生したCO2量から算出した。
<ガスクロマトグラフ操作条件>
機種:GC−14B[島津製作所]
検出器:TCD
カラム:Chromosorb101,80〜100mesh
ガラス管,φ3.2mm×2m
温度:カラム50℃,注入口及び検出器100℃
セル電流75mA
ガス圧力:ヘリウム(キャリヤーガス)100kPa
注入量:ヘッドスペースガス0.2mL
[Analysis of carbonate]
The method for analyzing the content of carbonate in the solid composition is as follows.
0.1 to 0.2 g of a solid composition was sampled, and 10 mL of water and 2 mL of 50% phosphoric acid were added and sealed. After sonication for 10 minutes, the sample was left for 1 hour, the head space gas was subjected to a gas chromatograph, the amount of CO 2 was determined, and the amount of CO 2 generated was calculated.
<Gas chromatograph operating conditions>
Model: GC-14B [Shimadzu Corporation]
Detector: TCD
Column: Chromosorb 101, 80-100 mesh
Glass tube, φ3.2mm × 2m
Temperature: Column 50 ° C, inlet and detector 100 ° C
Cell current 75mA
Gas pressure: Helium (carrier gas) 100 kPa
Injection volume: 0.2 mL of headspace gas
[有機酸の分析]
固形状組成物中の有機酸の含有量の分析方法は以下の通りである。
固形状組成物を1g採取し5%過塩素酸20mLを加え、10分間振とうすることで抽出した。これを水で200mLに定容し10分間超音波処理を行った。ろ過後高速液体クロマトグラフに供した。
<高速液体クロマトグラフ操作条件>
機種:LC−20AD[株式会社島津製作所]
検出器:紫外可視吸光光度計SPD−20AV[島津製作所]
カラム温度:40℃
移動相:3mmоl/L過塩素酸
反応液:0.2mmоl/Lブロムチモールブルー含有
15mmоl/Lりん酸水素二ナトリウム溶液
流量:移動相1.0mL/min、反応液1.4mL/min
測定波長:445nm
[Analysis of organic acids]
The analysis method of the content of the organic acid in the solid composition is as follows.
1 g of the solid composition was sampled, 20 mL of 5% perchloric acid was added, and the mixture was extracted by shaking for 10 minutes. This was made up to 200 mL with water and sonicated for 10 minutes. It used for the high performance liquid chromatograph after filtration.
<High-performance liquid chromatograph operating conditions>
Model: LC-20AD [Shimadzu Corporation]
Detector: UV-visible spectrophotometer SPD-20AV [Shimadzu Corporation]
Column temperature: 40 ° C
Mobile phase: 3 mmol / L perchloric acid reaction solution: 0.2 mmol / L bromthymol blue-containing 15 mmol / L disodium hydrogen phosphate solution Flow rate: mobile phase 1.0 mL / min, reaction solution 1.4 mL / min
Measurement wavelength: 445 nm
〔チュアブル錠の調製〕
実施例1〜実施例11及び比較例1〜比較例7
表1に記載の配合組成で各原料成分を混合した。次に単発式打錠機(RIKEN社製)を用いて、穴径7mmのリング状杵で、錠剤重量100mgで打錠し、チュアブル錠を得た。
[Preparation of chewable tablets]
Examples 1 to 11 and Comparative Examples 1 to 7
Each raw material component was mixed with the composition shown in Table 1. Next, using a single-type tableting machine (manufactured by RIKEN), the tablet was tableted with a tablet weight of 100 mg with a ring-shaped punch having a hole diameter of 7 mm to obtain chewable tablets.
上記で得た本発明品と比較品を専門パネル3名による官能評価を行なった。評価は、ヘスペリジン特有の後味の収斂味、ヘスペリジン特有の苦味、酸味と塩味のバランスについて、下記に示す判断基準に従って行い、協議により評点を決定した。結果を表1に示す。
〔後味の収斂味〕
5:後味の収斂味が弱い
4:後味の収斂味がやや弱い
3:後味の収斂味がやや強い
2:後味の収斂味が強い
1:後味の収斂味がとても強い
〔苦味〕
5:苦味が弱い
4:苦味がやや弱い
3:苦味がやや強い
2:苦味がが強い
1:苦味がとても強い
〔酸味と塩味のバランス〕
5:酸味と塩味が突出せずにバランスが非常に良い
4:酸味と塩味が突出せずにバランスが良い
3:酸味と塩味が突出せずにバランスがやや良い
2:塩味及び/又は酸味がやや強くバランスが悪い
1:塩味及び/又は酸味が強くバランスが非常に悪い
Sensory evaluation was performed by three specialist panels on the products of the present invention and comparative products obtained above. The evaluation was carried out according to the criteria shown below for the astringent taste specific to hesperidin, the bitter taste specific to hesperidin, and the balance between acidity and saltiness, and the score was determined through consultation. The results are shown in Table 1.
[Astringent taste of aftertaste]
5: Astringent taste of aftertaste is weak 4: Astringent taste of aftertaste is slightly weak 3: Astringent taste of aftertaste is slightly strong 2: Astringent taste of aftertaste is strong 1: Astringent taste of aftertaste is very strong [bitter taste]
5: The bitterness is weak 4: The bitterness is slightly weak 3: The bitterness is slightly strong 2: The bitterness is strong 1: The bitterness is very strong [balance between acidity and salty]
5: Very good balance without protruding sour and salty 4: Good balance without protruding sour and salty 3: Slightly balanced without protruding sour and salty 2: Salty and / or sour Slightly strong and unbalanced 1: Strong salty and / or sour, very poor balance
表1から明らかなように、ヘスペリジンを配合した固形状組成物は、ヘスペリジン特有の後に残る収斂味と苦味が感じられた(比較例6と7)。これに対し、本発明品は、比較品と比べ、ヘスペリジン特有の後に残る収斂味と苦味が低減されて、また、炭酸塩由来の塩味や有機酸由来の酸味が突出せず、風味のバランスが良好であった。
ヘスペリジンに対する炭酸塩の割合が一定範囲外の比較例1〜3は、ヘスペリジンの後に残る収斂味と苦味の低減効果が低く、有機酸と炭酸塩の当量比が一定範囲外の比較例4と5では、炭酸塩由来の塩味や有機酸由来の酸味が強く、風味のバランスが悪かった。
As is apparent from Table 1, the solid composition containing hesperidin felt the astringent taste and bitterness remaining after hesperidin (Comparative Examples 6 and 7). On the other hand, compared with the comparative product, the astringent taste and bitterness remaining after hesperidin is reduced in the present invention product, and the salty taste derived from carbonate and the sour taste derived from organic acid do not protrude, and the balance of flavor is It was good.
Comparative Examples 1 to 3 in which the ratio of carbonate to hesperidin is outside a certain range have a low effect of reducing the astringency and bitterness remaining after hesperidin, and Comparative Examples 4 and 5 in which the equivalent ratio of organic acid to carbonate is outside the certain range. Then, the saltiness derived from carbonate and the acidity derived from organic acid were strong, and the balance of flavor was bad.
Claims (5)
(A)ヘスペリジン及び/又はヘスペリジン誘導体、
(B)炭酸塩、
(C)有機酸、
を含有し、成分(A)と成分(B)の含有質量比[(B)/(A)]が0.25以上であり、且つ成分(C)と成分(B)の当量比[(C)の当量/(B)の当量]が0.8〜3である固形状組成物。 The following components (A), (B) and (C):
(A) hesperidin and / or hesperidin derivative,
(B) carbonate,
(C) an organic acid,
The mass ratio of component (A) to component (B) [(B) / (A)] is 0.25 or more, and the equivalent ratio of component (C) to component (B) [(C ) Equivalent / (B) equivalent] is 0.8-3.
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02295919A (en) * | 1989-04-28 | 1990-12-06 | Beecham Group Plc | Medical remedy |
JPH04327526A (en) * | 1991-04-26 | 1992-11-17 | Lion Corp | Solid pharmaceutical for oral use |
JP2004275089A (en) * | 2003-03-17 | 2004-10-07 | Ezaki Glico Co Ltd | Foaming roux |
JP2005053861A (en) * | 2003-08-06 | 2005-03-03 | Kao Corp | Solid composition |
JP2011126849A (en) * | 2009-12-21 | 2011-06-30 | Ito En Ltd | Hesperidin-containing beverage |
-
2013
- 2013-12-19 JP JP2013262439A patent/JP6253393B2/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02295919A (en) * | 1989-04-28 | 1990-12-06 | Beecham Group Plc | Medical remedy |
JPH04327526A (en) * | 1991-04-26 | 1992-11-17 | Lion Corp | Solid pharmaceutical for oral use |
JP2004275089A (en) * | 2003-03-17 | 2004-10-07 | Ezaki Glico Co Ltd | Foaming roux |
JP2005053861A (en) * | 2003-08-06 | 2005-03-03 | Kao Corp | Solid composition |
JP2011126849A (en) * | 2009-12-21 | 2011-06-30 | Ito En Ltd | Hesperidin-containing beverage |
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