JP4929628B2 - Zinc-containing oral solution - Google Patents
Zinc-containing oral solution Download PDFInfo
- Publication number
- JP4929628B2 JP4929628B2 JP2005196923A JP2005196923A JP4929628B2 JP 4929628 B2 JP4929628 B2 JP 4929628B2 JP 2005196923 A JP2005196923 A JP 2005196923A JP 2005196923 A JP2005196923 A JP 2005196923A JP 4929628 B2 JP4929628 B2 JP 4929628B2
- Authority
- JP
- Japan
- Prior art keywords
- zinc
- acid
- solution
- amino acids
- purified water
- 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.)
- Active
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- 239000011701 zinc Substances 0.000 title claims description 11
- 229910052725 zinc Inorganic materials 0.000 title claims description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims description 10
- 229940100688 oral solution Drugs 0.000 title claims description 5
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- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 10
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 7
- 239000011670 zinc gluconate Substances 0.000 claims description 7
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- 229940024606 amino acid Drugs 0.000 description 23
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
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- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960000510 ammonia Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- PLKYGPRDCKGEJH-UHFFFAOYSA-N azane;2-hydroxypropane-1,2,3-tricarboxylic acid;iron Chemical compound N.[Fe].OC(=O)CC(O)(C(O)=O)CC(O)=O PLKYGPRDCKGEJH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 description 1
- 229960000678 carnitine chloride Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- WPUMTJGUQUYPIV-JIZZDEOASA-L disodium (S)-malate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](O)CC([O-])=O WPUMTJGUQUYPIV-JIZZDEOASA-L 0.000 description 1
- 229950010030 dl-alanine Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960003707 glutamic acid hydrochloride Drugs 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000006286 nutrient intake Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
- 235000020957 pantothenol Nutrition 0.000 description 1
- 239000011619 pantothenol Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000019265 sodium DL-malate Nutrition 0.000 description 1
- 239000001394 sodium malate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011667 zinc carbonate Substances 0.000 description 1
- 235000004416 zinc carbonate Nutrition 0.000 description 1
- 229910000010 zinc carbonate Inorganic materials 0.000 description 1
- 229940043825 zinc carbonate Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 229960001939 zinc chloride Drugs 0.000 description 1
- 239000011746 zinc citrate Substances 0.000 description 1
- 235000006076 zinc citrate Nutrition 0.000 description 1
- 229940068475 zinc citrate Drugs 0.000 description 1
- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 description 1
- 229910000165 zinc phosphate Inorganic materials 0.000 description 1
- 229940077935 zinc phosphate Drugs 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、飲用するときの不快な味を低減した亜鉛含有内服液剤に関し、医薬および食品の分野に利用できるものである。 The present invention relates to a zinc-containing internal liquid that has reduced unpleasant taste when taken, and can be used in the fields of medicine and food.
亜鉛化合物を配合した液剤は亜鉛イオンに由来する不快な味のため飲みにくいものであった。この味は、タンニンやミョウバンなどのタンパクと結合する収斂剤を口にしたときの味(収斂味)と共通のものである。これまで、亜鉛化合物のような収斂性を有する化合物を含有する薬剤や食品の不快な味を改善するため、グリシン、アラニン等のアミノ酸を配合する技術が開示されている(特許文献1)。しかしながら、グリシンおよびアラニンでは亜鉛イオンに由来する不快な味を改善する効果は充分ではなかった。 A liquid preparation containing a zinc compound was difficult to drink due to an unpleasant taste derived from zinc ions. This taste is the same as the taste when using an astringent that binds to proteins such as tannin and alum (astringent taste). So far, a technique for blending amino acids such as glycine and alanine has been disclosed in order to improve the unpleasant taste of a drug or food containing a compound having astringency such as a zinc compound (Patent Document 1). However, glycine and alanine are not sufficient in improving the unpleasant taste derived from zinc ions.
本発明の目的は、亜鉛イオンに由来する収斂味を低減し、飲みやすく、しかも不快な後味が残らない亜鉛含有液剤を提供することである。 An object of the present invention is to provide a zinc-containing liquid agent that reduces the astringent taste derived from zinc ions, is easy to drink, and does not leave an unpleasant aftertaste.
上記課題を解決するために、本発明者らは、鋭意検討を重ねた結果、亜鉛化合物に塩基性アミノ酸、分岐鎖アミノ酸、酸性アミノ酸およびそのアミド、トリプトファン並びにこれらの塩からなる群から選ばれる1種又は2種以上のアミノ酸を配合すると、亜鉛イオンによるタンパクの凝集(収斂性)が低減し、収斂味が改善されることを見出し、本発明を完成した。 In order to solve the above problems, the present inventors have made extensive studies and as a result, the zinc compound is selected from the group consisting of basic amino acids, branched chain amino acids, acidic amino acids and amides thereof, tryptophan, and salts thereof. It has been found that when seeds or two or more amino acids are added, protein aggregation (convergence) due to zinc ions is reduced, and the astringent taste is improved, and the present invention has been completed.
すなわち、本発明は、亜鉛化合物に特定のアミノ酸(塩基性アミノ酸、分岐鎖アミノ酸、酸性アミノ酸およびそのアミド、トリプトファン並びにこれらの塩からなる群から選ばれる1種又は2種以上)を配合した亜鉛含有内服液剤である。 That is, the present invention includes a zinc compound containing a specific amino acid (one or more selected from the group consisting of basic amino acids, branched chain amino acids, acidic amino acids and their amides, tryptophan, and salts thereof). It is an internal solution.
本発明における亜鉛化合物とは、亜鉛を含む塩であり、塩を形成する酸は無毒性であれば有機酸又は無機酸のどちらでもかまわず、有機酸としては例えば、乳酸、グルコン酸、クエン酸、リンゴ酸、酒石酸等の有機酸を、また無機酸としては、例えば、硫酸、炭酸、塩酸、リン酸、硝酸等を挙げることができる。好ましい亜鉛化合物としては、例えば、グルコン酸亜鉛、硫酸亜鉛、クエン酸亜鉛、炭酸亜鉛、塩化亜鉛、リン酸亜鉛などが挙げられる。これらは、単独で配合してもよく、2種以上を組み合わせて配合してもよい。 The zinc compound in the present invention is a salt containing zinc, and the acid forming the salt may be either an organic acid or an inorganic acid as long as it is non-toxic. Examples of the organic acid include lactic acid, gluconic acid, and citric acid. Organic acids such as malic acid and tartaric acid, and inorganic acids include sulfuric acid, carbonic acid, hydrochloric acid, phosphoric acid, nitric acid and the like. Preferred zinc compounds include, for example, zinc gluconate, zinc sulfate, zinc citrate, zinc carbonate, zinc chloride, zinc phosphate and the like. These may be blended singly or in combination of two or more.
亜鉛化合物の配合量は、これを配合する内服液剤の使用目的により異なる。栄養摂取量の面からは、亜鉛イオンに換算して、1日当たり1〜50mgが好ましく、1日に100mlの内服液剤として摂取する場合、その亜鉛イオン濃度は、0.001〜0.05W/V%である。 The compounding quantity of a zinc compound changes with the intended purpose of the internal use liquid agent which mix | blends this. In terms of nutrient intake, 1 to 50 mg per day is preferable in terms of zinc ions, and when taken as a 100 ml oral solution per day, the zinc ion concentration is 0.001 to 0.05 W / V. %.
本発明における特定のアミノ酸とは、塩基性アミノ酸(アルギニン、ヒスチジンおよびリジン)、分岐鎖アミノ酸(バリン、ロイシンおよびイソロイシン)、酸性アミノ酸(アスパラギン酸およびグルタミン酸)およびそのアミド(アスパラギン、グルタミン)、トリプトファン並びにその塩である。該アミノ酸塩には、酸(塩酸、硫酸、メタンスルホン酸など)、塩基(アンモニア、ナトリウム、カリウム、カルシウム、マグネシウムなど)又は他のアミノ酸との塩が挙げられる。本発明においては、これら特定のアミノ酸から1種又は2種以上を選んで配合できるが、特に好ましいアミノ酸は、分岐鎖アミノ酸、酸性アミノ酸のアミドおよびトリプトファンであり、さらに好ましくはトリプトファンである。 Specific amino acids in the present invention include basic amino acids (arginine, histidine and lysine), branched chain amino acids (valine, leucine and isoleucine), acidic amino acids (aspartic acid and glutamic acid) and their amides (asparagine and glutamine), tryptophan and Its salt. The amino acid salts include salts with acids (hydrochloric acid, sulfuric acid, methanesulfonic acid, etc.), bases (ammonia, sodium, potassium, calcium, magnesium, etc.) or other amino acids. In the present invention, one or more of these specific amino acids can be selected and added. Particularly preferred amino acids are branched chain amino acids, amides of acidic amino acids, and tryptophan, and more preferably tryptophan.
亜鉛化合物と特定のアミノ酸との配合比は、その亜鉛イオン1質量部に対し0.1質量部以上であり、好ましくは1〜4000質量部、さらに好ましくは2.5〜2000質量部である。 The compounding ratio of the zinc compound and the specific amino acid is 0.1 parts by mass or more with respect to 1 part by mass of the zinc ions, preferably 1 to 4000 parts by mass, and more preferably 2.5 to 2000 parts by mass.
本発明の亜鉛含有内服液剤のpHは、2.5〜7.0であり、好ましくは3.0〜5.5である。この内服液剤のpHは、例えば、クエン酸、リンゴ酸、フマル酸、酒石酸、乳酸、コハク酸などの有機酸、これら有機酸の塩、リン酸、塩酸などの無機酸、水酸化ナトリウムなどの無機塩基を添加して調整できる。 The pH of the zinc-containing oral solution of the present invention is 2.5 to 7.0, preferably 3.0 to 5.5. The pH of the internal solution is, for example, organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid, succinic acid, salts of these organic acids, inorganic acids such as phosphoric acid and hydrochloric acid, inorganic acids such as sodium hydroxide, etc. It can be adjusted by adding a base.
本発明の亜鉛含有内服液剤には、ビタミン類、ミネラル類、他のアミノ酸類、生薬、生薬抽出物、カフェイン、ローヤルゼリーなどを本発明の効果を損なわない範囲で適宜に配合できる。また、必要に応じて抗酸化剤、着色剤、香料、矯味剤、界面活性剤、溶解補助剤、保存剤、甘味料などの添加物を本発明の効果を損なわない範囲で適宜に配合できる。 Vitamins, minerals, other amino acids, herbal medicines, herbal extracts, caffeine, royal jelly, and the like can be appropriately added to the zinc-containing internal liquid of the present invention as long as the effects of the present invention are not impaired. Moreover, additives such as antioxidants, colorants, flavors, flavoring agents, surfactants, solubilizers, preservatives, sweeteners, and the like can be appropriately blended as necessary so long as the effects of the present invention are not impaired.
本発明の亜鉛含有内服液剤を調製する方法は特に限定されるものではない。通常、各成分を適量の精製水で溶解した後、pHを調整し、残りの精製水を加えて容量調整し、必要に応じて濾過、滅菌処理することにより目的の亜鉛含有内服液剤が得られる。 The method for preparing the zinc-containing internal solution of the present invention is not particularly limited. Usually, after dissolving each component with an appropriate amount of purified water, the pH is adjusted, the remaining purified water is added to adjust the volume, and if necessary, filtration and sterilization are performed to obtain the desired zinc-containing internal solution. .
以下に実施例及び試験例を挙げ、本発明をより詳しく説明する。 Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples.
実施例1
グルコン酸亜鉛 0.04g
トリプトファン 0.20g
塩酸アルギニン 0.20g
グルコン酸カルシウム 2.00g
アスパラギン酸マグネシウム 1.00g
硝酸チアミン 0.01g
リボフラビン 0.01g
塩酸ピリドキシン 0.10g
アスコルビン酸 1.00g
アミノエチルスルホン酸 1.00g
ソルビトール 4.00g
トレハロース 5.00g
キシリトール 4.00g
ステビア抽出物 0.03g
アセスルファムカリウム 0.03g
リンゴ酸 0.10g
クエン酸 0.40g
クエン酸ナトリウム 適量
安息香酸 0.06g
パラオキシ安息香酸ブチル 0.006g
パラオキシ安息香酸プロピル 0.006g
アップルフレーバー 0.10g
上記成分を精製水に溶解した後、pHを4.0に調整し、精製水を加えて全量を100mLとした。この液をろ紙でろ過し、滅菌装置を用いて、ろ液を80℃で25分間加熱滅菌した後、ガラス瓶に充填しキャップを施して内服液剤を得た。
Example 1
Zinc gluconate 0.04g
Tryptophan 0.20g
Arginine hydrochloride 0.20g
Calcium gluconate 2.00g
Magnesium aspartate 1.00 g
0.01 g of thiamine nitrate
Riboflavin 0.01g
0.10 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Aminoethylsulfonic acid 1.00g
Sorbitol 4.00g
Trehalose 5.00g
Xylitol 4.00g
Stevia extract 0.03g
Acesulfame potassium 0.03g
Malic acid 0.10g
Citric acid 0.40g
Sodium citrate appropriate amount Benzoic acid 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
Apple flavor 0.10g
After dissolving the above components in purified water, the pH was adjusted to 4.0, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.
実施例2
グルコン酸亜鉛 0.08g
グルタミン塩酸塩 0.10g
ロイシン 0.20g
イソロイシン 0.20g
バリン 0.20g
リボフラビン 0.01g
塩酸ピリドキシン 0.01g
アスコルビン酸 1.00g
シアノコバラミン 120μg
パンテノール 0.01g
ニコチン酸アミド 0.05g
アミノエチルスルホン酸 1.00g
ソルビトール 5.00g
トレハロース 2.00g
マルチトール 2.00g
クエン酸 0.40g
リンゴ酸ナトリウム 適量
安息香酸 0.06g
パラオキシ安息香酸ブチル 0.006g
パラオキシ安息香酸プロピル 0.006g
ミックスフルーツフレーバー 0.10g
上記成分を精製水に溶解した後、pHを4.5に調整し、精製水を加えて全量を100mLとした。この液をろ紙でろ過し、滅菌装置を用いて、ろ液を80℃で25分間加熱滅菌した後、ガラス瓶に充填しキャップを施して内服液剤を得た。
Example 2
Zinc gluconate 0.08g
Glutamine hydrochloride 0.10g
Leucine 0.20g
Isoleucine 0.20g
Valine 0.20g
Riboflavin 0.01g
0.01 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Cyanocobalamin 120μg
Panthenol 0.01g
Nicotinamide 0.05g
Aminoethylsulfonic acid 1.00g
Sorbitol 5.00g
Trehalose 2.00g
Maltitol 2.00g
Citric acid 0.40g
Sodium malate appropriate amount Benzoic acid 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 4.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.
実施例3
グルコン酸亜鉛 0.08g
ヒスチジン塩酸塩 0.30g
塩酸アルギニン 0.20g
グルコン酸カルシウム 0.80g
アスパラギン酸マグネシウム 0.40g
アスパラギン酸ナトリウム 0.30g
硝酸チアミン 0.01g
リン酸リボフラビンナトリウム 0.01g
塩酸ピリドキシン 0.01g
ニコチン酸アミド 0.10g
無水カフェイン 0.10g
アミノエチルスルホン酸 2.00g
ヨクイニン流エキス 2.00mL
ブドウ糖 5.00g
難消化性デキストリン 4.00g
エリスリトール 5.00g
キシリトール 2.00g
ステビア抽出物 0.02g
アセスルファムカリウム 0.03g
スクラロース 0.05g
クエン酸 0.80g
クエン酸ナトリウム 適量
安息香酸ナトリウム 0.06g
パラオキシ安息香酸ブチル 0.006g
パラオキシ安息香酸プロピル 0.006g
ミックスフルーツフレーバー 0.10g
上記成分を精製水に溶解した後、pHを3.5に調整し、精製水を加え全量を100mLとした。この液をろ紙でろ過し、滅菌装置を用いて、ろ液を80℃で25分間加熱滅菌した後、ガラス瓶に充填しキャップを施して内服液剤を得た。
Example 3
Zinc gluconate 0.08g
Histidine hydrochloride 0.30g
Arginine hydrochloride 0.20g
Calcium gluconate 0.80 g
Magnesium aspartate 0.40 g
Sodium aspartate 0.30g
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.01 g
0.01 g of pyridoxine hydrochloride
Nicotinamide 0.10g
Anhydrous caffeine 0.10g
Aminoethylsulfonic acid 2.00g
Yokuinin style extract 2.00mL
Glucose 5.00g
Indigestible dextrin 4.00 g
Erythritol 5.00g
Xylitol 2.00g
Stevia extract 0.02g
Acesulfame potassium 0.03g
Sucralose 0.05g
Citric acid 0.80 g
Sodium citrate appropriate amount Sodium benzoate 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 3.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.
実施例4
グルコン酸亜鉛 0.01g
ヒスチジン塩酸塩 0.20g
塩化カルニチン 0.20g
グリシン 0.20g
グルコン酸カルシウム 0.20g
乳酸カルシウム 0.20g
アスパラギン酸ナトリウム 0.10g
塩化マグネシウム 0.06g
クエン酸鉄アンモニウム 0.04g
硝酸チアミン 0.01g
リン酸リボフラビンナトリウム 0.02g
塩酸ピリドキシン 0.03g
ニコチン酸アミド 0.05g
無水カフェイン 0.10g
アミノエチルスルホン酸 2.00g
ヨクイニン流エキス 2.00mL
ローヤルゼリー 0.60g
ブドウ糖 5.00g
ソルビトール 5.00g
キシリトール 5.00g
ステビア抽出物 0.02g
アセスルファムカリウム 0.03g
クエン酸 0.80g
クエン酸ナトリウム 0.10g
リン酸 0.30g
塩酸 適量
安息香酸ナトリウム 0.06g
パラオキシ安息香酸ブチル 0.006g
パラオキシ安息香酸プロピル 0.006g
ミックスフルーツフレーバー 0.10g
上記成分を精製水に溶解した後、pHを3.5に調整し、精製水を加え全量を100mLとした。この液をろ紙でろ過し、滅菌装置を用いて、ろ液を80℃で25分間加熱滅菌した後、ガラス瓶に充填しキャップを施して内服液剤を得た。
Example 4
Zinc gluconate 0.01g
Histidine hydrochloride 0.20g
Carnitine chloride 0.20g
Glycine 0.20g
Calcium gluconate 0.20g
Calcium lactate 0.20g
Sodium aspartate 0.10g
Magnesium chloride 0.06g
0.04 g of ammonium iron citrate
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.02g
0.03 g of pyridoxine hydrochloride
Nicotinamide 0.05g
Anhydrous caffeine 0.10g
Aminoethylsulfonic acid 2.00g
Yokuinin style extract 2.00mL
Royal jelly 0.60g
Glucose 5.00g
Sorbitol 5.00g
Xylitol 5.00g
Stevia extract 0.02g
Acesulfame potassium 0.03g
Citric acid 0.80 g
Sodium citrate 0.10g
Phosphoric acid 0.30 g
Hydrochloric acid appropriate amount Sodium benzoate 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 3.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.
試験例
Hagermanらは、溶液中のタンパク(ウシ血清アルブミン:BSA)がタンニンにより凝集し、その沈澱量はタンニンの量に比例することを報告した(J.Agric.Food.Chem.,1978,Vol.26,809-812)。本発明者らは、亜鉛イオン溶液にBSA溶液を加えると、この溶液が懸濁し、吸光度が上昇すること、この吸光度の上昇が、亜鉛イオンの濃度に相関することを見出した。これは、ある物質を添加した亜鉛イオン溶液をBSA溶液に混合したときの吸光度が無添加の場合と比較して減少すると、その物質の添加により、タンパク−亜鉛イオン相互作用による凝集(収斂性)が減少したこと、すなわち収斂味が減少したことを意味すると考えられる。
Test example
Hagerman et al. Reported that protein (bovine serum albumin: BSA) in solution was aggregated by tannin, and the amount of precipitation was proportional to the amount of tannin ( J. Agric . Food . Chem ., 1978, Vol. 26 , 809) . -812). The present inventors have found that the addition of BSA solution to a zinc ion solution, the solution was suspended, the absorbance increases, increase in absorbance was found to correlate with the concentration of zinc ions. This is because, when the absorbance when a zinc ion solution containing a certain substance is mixed with a BSA solution decreases compared to the case where no addition is made, the addition of that substance causes aggregation due to protein-zinc ion interaction (convergence). Is considered to mean that the astringent taste has decreased.
試験方法
1)BSA溶液の調製
BSA(Sigma Chemical Co.;fraction V,fatty acid free)10gを適量の精製水に溶解し、クエン酸100mgを加え、NaOH溶液(1mol/L)でpHを4.8に調整し、精製水で100mLとした。
2)希釈液の調製
クエン酸100mgを適量の水に溶解し、NaOH溶液(1mol/L)でpHを4.8に調整し、精製水で100mLとした。
3)亜鉛イオン溶液の調製
グルコン酸亜鉛0.04g、0.19gおよび0.39gにクエン酸0.10gを加えた。それぞれを適量の精製水に溶解し、NaOH溶液(1mol/L)でpHを4.8に調整し、精製水で100mLとした。
4)タンパク−亜鉛イオン相互作用(収斂性)の評価
各亜鉛イオン溶液2mLにBSA溶液6mLを加え、希釈液でそれぞれ全量を10mLとした。これを40℃で30分間振とうした。石英セル(L=1cm)を使用し、分光光度計(日立製作所製:U−3300)により、各透明溶液では吸収されない波長である500nmにおける吸光度を測定した。結果を図1に示す。
Test method 1) Preparation of BSA solution
Dissolve 10 g of BSA (Sigma Chemical Co .; fraction V, fatty acid free) in a suitable amount of purified water, add 100 mg of citric acid, adjust the pH to 4.8 with NaOH solution (1 mol / L), and use purified water. 100 mL.
2) Preparation of diluent
100 mg of citric acid was dissolved in an appropriate amount of water, the pH was adjusted to 4.8 with NaOH solution (1 mol / L), and adjusted to 100 mL with purified water.
3) Preparation of zinc ion solution
To 0.04 g, 0.19 g, and 0.39 g of zinc gluconate was added 0.10 g of citric acid. Each was dissolved in an appropriate amount of purified water, adjusted to pH 4.8 with NaOH solution (1 mol / L), and made up to 100 mL with purified water.
4) Evaluation of protein-zinc ion interaction (convergence) 6 mL of BSA solution was added to 2 mL of each zinc ion solution, and the total volume was adjusted to 10 mL with a diluting solution. This was shaken at 40 ° C. for 30 minutes. Using a quartz cell (L = 1 cm), the absorbance at 500 nm, which is a wavelength that is not absorbed by each transparent solution, was measured with a spectrophotometer (manufactured by Hitachi, Ltd .: U-3300). The results are shown in FIG.
次に、各種濃度の亜鉛イオン溶液と収斂味(官能評価)との相関を調べた。官能評価は、収斂味が強くて許容できない場合をB、許容することができる範囲をその収斂味の強さに応じてA4〜A1とし、収斂味を全く感じない場合をAとして評価を行った。その結果を図2に示す。図2より、吸光度が約0.4以下であれば、亜鉛イオン由来の収斂味が十分抑制されていると判断した。 Next, the correlation between various concentrations of zinc ion solution and astringency (sensory evaluation) was examined. The sensory evaluation was evaluated as B when the astringent taste was strong and unacceptable, A4 to A1 depending on the strength of the astringent taste, and A when the astringent taste was not felt at all. . The result is shown in FIG. From FIG. 2, it was determined that the astringent taste derived from zinc ions was sufficiently suppressed when the absorbance was about 0.4 or less.
5)各種アミノ酸のタンパク凝集性
表1に示す処方の液剤を調製した後、塩基性アミノ酸(アルギニン塩酸塩、ヒスチジン塩酸塩およびリジン塩酸塩)、中性アミノ酸(トリプトファン、DL−アラニン、グリシン)、酸性アミノ酸(グルタミン酸塩酸塩、アスパラギン酸ナトリウム)およびそのアミド(グルタミン)、分岐鎖アミノ酸(バリン、ロイシン、イソロイシン)の各種アミノ酸を測定時の濃度がそれぞれ100mg、500mg/100mLとなるように添加して、4)に記載の方法により各種アミノ酸のタンパク凝集性を評価した。結果を表2に示す。表2より、分岐鎖アミノ酸、酸性アミノ酸およびそのアミド、トリプトファンにタンパク凝集の抑制作用が確認された。また、トリプトファン、ロイシン、イソロイシンおよびグルタミンは、特に優れたタンパク凝集の抑制作用、すなわち収斂味の改善に優れていることが明らかとなった。
5) Protein aggregation of various amino acids
After preparing the liquid formulation of the formulation shown in Table 1, basic amino acids (arginine hydrochloride, histidine hydrochloride and lysine hydrochloride), neutral amino acids (tryptophan, DL-alanine, glycine), acidic amino acids (glutamic acid hydrochloride, asparagine) Acid) and its amide (glutamine) and branched chain amino acids (valine, leucine, isoleucine) were added so that the concentrations at the time of measurement were 100 mg and 500 mg / 100 mL, respectively, and the method described in 4) The protein aggregation property of various amino acids was evaluated. The results are shown in Table 2. From Table 2, it was confirmed that branched chain amino acids, acidic amino acids and their amides, and tryptophan have an inhibitory effect on protein aggregation. In addition, it was revealed that tryptophan, leucine, isoleucine and glutamine are particularly excellent in suppressing the protein aggregation, that is, in improving the astringent taste.
本発明により、亜鉛イオンに由来する収斂味を低減し、飲みやすく、しかも不快な後味が残らない亜鉛含有内服液剤を提供することができた。
この亜鉛含有内服液剤は、例えば、シロップ剤、ドリンク剤などの医薬品や医薬部外品を含む各種製剤及び栄養機能食品などの各種飲料に適用できる。
According to the present invention, an astringent taste derived from zinc ions can be reduced, an easy-to-drink zinc-containing oral solution that does not leave an unpleasant aftertaste can be provided.
This zinc-containing internal solution can be applied to, for example, various preparations including pharmaceuticals such as syrups and drinks and quasi-drugs, and various beverages such as nutritional functional foods.
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