JP2009018993A - Uncomfortable taste-masked quinolone-based antibiotic oral administration liquid medicine - Google Patents
Uncomfortable taste-masked quinolone-based antibiotic oral administration liquid medicine Download PDFInfo
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- JP2009018993A JP2009018993A JP2007180790A JP2007180790A JP2009018993A JP 2009018993 A JP2009018993 A JP 2009018993A JP 2007180790 A JP2007180790 A JP 2007180790A JP 2007180790 A JP2007180790 A JP 2007180790A JP 2009018993 A JP2009018993 A JP 2009018993A
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- 239000007788 liquid Substances 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 title claims abstract description 8
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title claims abstract 5
- 230000003115 biocidal effect Effects 0.000 title abstract 5
- 235000019640 taste Nutrition 0.000 claims abstract description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 24
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000001014 amino acid Nutrition 0.000 claims abstract description 11
- 150000001413 amino acids Chemical class 0.000 claims abstract description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 8
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004310 lactic acid Substances 0.000 claims abstract description 8
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 8
- 150000007524 organic acids Chemical class 0.000 claims abstract description 8
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims abstract description 7
- 229960003376 levofloxacin Drugs 0.000 claims abstract description 6
- 229960001180 norfloxacin Drugs 0.000 claims abstract description 5
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 claims abstract description 4
- WUWFMDMBOJLQIV-UHFFFAOYSA-N 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid Chemical compound C1C(N)CCN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1F WUWFMDMBOJLQIV-UHFFFAOYSA-N 0.000 claims abstract description 4
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000004471 Glycine Substances 0.000 claims abstract description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims abstract description 4
- 229930064664 L-arginine Natural products 0.000 claims abstract description 4
- 235000014852 L-arginine Nutrition 0.000 claims abstract description 4
- 229960003405 ciprofloxacin Drugs 0.000 claims abstract description 4
- 229960002549 enoxacin Drugs 0.000 claims abstract description 4
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960003923 gatifloxacin Drugs 0.000 claims abstract description 4
- 229960002422 lomefloxacin Drugs 0.000 claims abstract description 4
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 claims abstract description 4
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 claims abstract description 4
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960001699 ofloxacin Drugs 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 claims abstract description 4
- 229960004954 sparfloxacin Drugs 0.000 claims abstract description 4
- 229950008187 tosufloxacin Drugs 0.000 claims abstract description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 11
- 229940072132 quinolone antibacterials Drugs 0.000 claims description 11
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- 239000004376 Sucralose Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 235000019408 sucralose Nutrition 0.000 claims description 5
- 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 claims description 5
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 230000000873 masking effect Effects 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- 150000007660 quinolones Chemical class 0.000 abstract description 3
- XBJBPGROQZJDOJ-UHFFFAOYSA-N fleroxacin Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(CCF)C2=C1F XBJBPGROQZJDOJ-UHFFFAOYSA-N 0.000 abstract description 2
- 229960003306 fleroxacin Drugs 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 8
- 230000001953 sensory effect Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 235000010356 sorbitol Nutrition 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940100688 oral solution Drugs 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 108010011485 Aspartame Proteins 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 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 1
- 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 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 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 1
- 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 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000019414 erythritol Nutrition 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
- 229940009714 erythritol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- -1 fleloxacin Chemical compound 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 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、キノロン系抗菌剤の不快な味をマスキングした経口投与用液剤に関する。 The present invention relates to a liquid for oral administration in which the unpleasant taste of a quinolone antibacterial agent is masked.
エノキサシン、ロメフロキサシン、オフロキサシン、ガチフロキサシン、シプロフロキサシン、スパルフロキサシン、トスフロキサシン、フレロキサシン、レボフロキサシンおよびノルフロキサシンに代表されるキノロン誘導体抗菌剤は、強烈に苦い不快な味を持っていることが知られている。従ってこれらの薬物の経口用製剤において不快な味をマスキングしなければならない。錠剤、顆粒、粉末のような固形製剤においては、不快な味を感じる口腔内でキノロン系抗菌薬物の溶解を阻止する製剤技術が有効である。そのような製剤技術は薬物または製剤を水不溶性化合物またはポリマーでコーティングすることを含み、特許文献１およびそれに引用されている文献に高級脂肪酸や医薬製剤の分野で使用される化合物およびポリマーが開示されている。 Quinolone derivatives such as enoxacin, lomefloxacin, ofloxacin, gatifloxacin, ciprofloxacin, sparfloxacin, tosufloxacin, fleloxacin, levofloxacin and norfloxacin are known to have an intensely bitter and unpleasant taste. It has been. Therefore, an unpleasant taste must be masked in oral preparations of these drugs. For solid preparations such as tablets, granules, and powders, a preparation technique that prevents dissolution of quinolone antibacterial drugs in the oral cavity that feels an unpleasant taste is effective. Such formulation techniques include coating a drug or formulation with a water-insoluble compound or polymer, and Patent Literature 1 and the literature cited therein disclose compounds and polymers used in the field of higher fatty acids and pharmaceutical formulations. ing.
ところが水不溶性の化合物またはポリマーでコーティングしたり、マイクロカプセル化する技術は経口投与される液剤には適用できない。液剤において薬物の不快な味をマスキングないし軽減するために一般に行われる方法は、甘味剤などの矯味剤を添加することである。キノロン誘導体抗菌薬物の場合、強烈な苦味を有するため、甘味剤や通常使用される矯味剤ではマスキング効果が不十分である。経口投与用液剤は、小児や高齢者にとっても服用が容易であることが意図されるから、小児や高齢者にとっても服用が容易な程度に不快な味がマスキングされたキノロン系抗菌剤の経口投与用液剤の提供が要望されている。 However, the technique of coating with a water-insoluble compound or polymer or microencapsulation cannot be applied to a liquid that is orally administered. A commonly practiced method for masking or reducing the unpleasant taste of a drug in a solution is to add a corrigent such as a sweetener. In the case of a quinolone derivative antibacterial drug, since it has an intense bitter taste, a masking effect is insufficient with a sweetener or a commonly used corrigent. Oral liquids are intended to be easily taken by children and the elderly, so oral administration of quinolone antibacterial agents masked with an unpleasant taste that can be easily taken by children and the elderly There is a demand for providing liquid preparations.
本発明は、エノキサシン、ロメフロキサシン、オフロキサシン、ガチフロキサシン、シプロフロキサシン、スパルフロキサシン、トスフロキサシン、フレロキサシン、レボフロキサシンまたはノルフロキサシンから選ばれたキノロン系抗菌剤と、キノロン系抗菌剤の不快な味をマスキングするのに有効な濃度の酢酸または乳酸から選ばれた有機酸と、グリシン、Ｌ−アルギニンまたはＬ−グルタミン酸モノナトリウムから選ばれたアミノ酸を含有することを特徴とするキノロン系抗菌剤の経口投与用液剤を提供する。 The present invention provides an unpleasant taste of quinolone antibacterial agents selected from enoxacin, lomefloxacin, ofloxacin, gatifloxacin, ciprofloxacin, sparfloxacin, tosufloxacin, fleroxacin, levofloxacin or norfloxacin, and quinolone antibacterial agents. Oral administration of a quinolone antibacterial agent characterized by containing an organic acid selected from acetic acid or lactic acid at a concentration effective for masking and an amino acid selected from glycine, L-arginine or monosodium L-glutamate A liquid preparation is provided.
本発明は、後記の味覚官能試験によって液剤におけるキノロン系抗菌剤の強烈に苦い不快な味は、酢酸または乳酸から選ばれる有機酸と、グリシン、Ｌ−アルギニンまたはＬ−グルタミン酸モノナトリウムから選ばれるアミノ酸の併用によって効果的にマスキングされるとの知見を基礎にしている。 According to the present invention, the intensely bitter and unpleasant taste of the quinolone antibacterial agent in the liquid agent according to the taste sensory test described below is an organic acid selected from acetic acid or lactic acid, and an amino acid selected from glycine, L-arginine, or monosodium L-glutamate. It is based on the knowledge that it is effectively masked by the combined use.
官能試験に使用したキノロン系抗菌剤はレボフロキサシンであるが、他のキノロン系抗菌剤も同様に強烈に苦い不快な味を有するので上の有機酸とアミノ酸の併用はそれらの不快な味のマスキングに効果があることは明らかである。 The quinolone antibacterial agent used in the sensory test is levofloxacin, but other quinolone antibacterial agents also have an intensely bitter and unpleasant taste, so the combination of the above organic acids and amino acids can mask those unpleasant tastes. It is clear that there is an effect.
酢酸または乳酸から選ばれる有機酸の濃度はマスキングに有効な濃度でなければならない。しかしながら過剰に高濃度である必要もなく、却って不適切であろう。従って０．２〜２ｗｔ／ｖ％の濃度が適切である。同様な理由で、アミノ酸またはその塩の濃度も０．５〜２ｗｔ／ｖ％が適切である。有機酸およびアミノ酸の２種類以上を併用する場合の濃度も上記範囲が適切である。 The concentration of the organic acid selected from acetic acid or lactic acid must be a concentration effective for masking. However, it does not have to be excessively high and would be inappropriate. Therefore, a concentration of 0.2 to 2 wt / v% is appropriate. For the same reason, the concentration of amino acid or a salt thereof is suitably 0.5 to 2 wt / v%. The above range is also appropriate for the concentration when two or more of organic acids and amino acids are used in combination.
本発明の経口液剤は、ポビドン、グリセリン、ヒドロキシエチルセルロース等の粘稠剤、安息香酸ナトリウム、ソルビン酸カリウム、エデト酸ナトリウム等の保存剤、アスパルテーム、還元麦芽糖水アメ、果糖、エリスリトール、ソルビトール、キシリトール、サッカリンナトリウム、スクラロース、乳糖、白糖、ブドウ糖等の甘味剤、着色剤、香料等の慣用の添加剤を含むことができる。 The oral solution of the present invention is a thickener such as povidone, glycerin, hydroxyethyl cellulose, preservatives such as sodium benzoate, potassium sorbate, sodium edetate, aspartame, reduced maltose water candy, fructose, erythritol, sorbitol, xylitol, Conventional additives such as sweeteners such as saccharin sodium, sucralose, lactose, sucrose, and glucose, colorants, and flavors can be included.
甘味剤としてはソルビトールまたはスクラロースが好ましく、特にソルビトールおよびスクラロースの組み合わせが好ましい。 As the sweetening agent, sorbitol or sucralose is preferable, and a combination of sorbitol and sucralose is particularly preferable.
ソルビトールの配合量としては、経口液剤全量に対し、好ましくは１０〜６０（Ｗ／Ｖ）％、特に好ましくは１５〜３０（Ｗ／Ｖ）％である。 The blending amount of sorbitol is preferably 10 to 60 (W / V)%, particularly preferably 15 to 30 (W / V)%, based on the total amount of the oral solution.
スクラロースの配合量としては、経口液剤全量に対し、好ましくは０．０１〜２（Ｗ／Ｖ）％、特に好ましくは０．１〜１（Ｗ／Ｖ）％である。 The blending amount of sucralose is preferably 0.01 to 2 (W / V)%, particularly preferably 0.1 to 1 (W / V)%, based on the total amount of the oral solution.
実施例１（乳酸及び酢酸による不快な味の遮蔽効果）
表１に示した各成分を適当な量の精製水に投入し、完全に溶解が確認されるまで十分に攪拌後、精製水を加えて全量を１００ｍＬとした液を味覚官能試験に用いた。
Example 1 (shielding effect of unpleasant taste by lactic acid and acetic acid)
Each component shown in Table 1 was put into an appropriate amount of purified water, stirred sufficiently until complete dissolution was confirmed, and then purified water was added to make a total volume of 100 mL for the taste sensory test.
５人のパネラーを対象として味覚官能試験を実施し、不快な味の遮蔽効果を検証した。評価方法としては、各液剤を口に含んだ直後と約１０秒後に吐き出した後の各時点での「甘さ」や「苦さ」から総合的に判断して、好ましい（５点）、やや好ましい（４点）、普通（３点）、やや不快（２点）、不快（１点）、非常に不快（０点）の６段階で回答してもらい、対照との差を改善度として評価し表２に示した。 A taste sensory test was conducted on five panelists to verify the shielding effect of unpleasant taste. As an evaluation method, it is preferable to judge comprehensively from “sweetness” and “bitterness” at each time point immediately after each liquid agent is contained in the mouth and after about 10 seconds after it is discharged (five points). 6 levels of answers (preferable (4 points), normal (3 points), slightly uncomfortable (2 points), uncomfortable (1 point), and very uncomfortable (0 points), and the difference from the control is evaluated as the improvement. It is shown in Table 2.
表２に示すように、乳酸及び酢酸による不快な味の遮蔽効果が確認された。 As shown in Table 2, an unpleasant taste shielding effect by lactic acid and acetic acid was confirmed.
実施例２（アミノ酸による不快な味の遮蔽効果）
表３に示した各成分を用い、実施例１と同様にして製造した液の味覚官能試験を行った。
Example 2 (shielding effect of unpleasant taste by amino acids)
Using each component shown in Table 3, a taste sensory test of the liquid produced in the same manner as in Example 1 was performed.
処方例１〜３と同様に味覚官能試験を実施し、改善度を表４に示した。 A taste sensory test was performed in the same manner as in Formulation Examples 1 to 3, and the degree of improvement is shown in Table 4.
表４に示すように、アミノ酸による不快な味の遮蔽効果が確認された。 As shown in Table 4, an unpleasant taste shielding effect by amino acids was confirmed.
実施例３（組合せによる不快な味の遮蔽効果）
表５に示した各成分を用い、実施例１と同様にして製造した液の味覚官能試験を行った。
Example 3 (shielding effect of unpleasant taste by combination)
Using each component shown in Table 5, a taste sensory test was performed on the liquid produced in the same manner as in Example 1.
処方例１〜３と同様に味覚官能試験を実施し、改善度を表６に示した。 A taste sensory test was performed in the same manner as in Formulation Examples 1 to 3, and the degree of improvement is shown in Table 6.
表６に示すように、酢酸または乳酸のいずれかとアミノ酸の組合せによる不快な味の遮蔽効果が確認された。 As shown in Table 6, an unpleasant taste shielding effect was confirmed by a combination of either acetic acid or lactic acid and an amino acid.
製造例
製造例として挙げた液剤は、実施例と同様にして製造される。これらの処方を表７に示す。
Manufacture example The liquid agent quoted as a manufacture example is manufactured like the Example. These formulations are shown in Table 7.
Claims (5)
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Cited By (2)
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| JP2013155142A (en) * | 2012-01-31 | 2013-08-15 | Towa Yakuhin Kk | Bitter-masked oral solution of quinolone-based antimicrobial agent |
| CN110141550A (en) * | 2019-07-09 | 2019-08-20 | 武汉兴华智慧医药科技有限公司 | A kind of lavo-ofloxacin oral administration solution and preparation method thereof |
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| JP2003171314A (en) * | 2001-09-26 | 2003-06-20 | Lion Corp | Oral administration solution composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013155142A (en) * | 2012-01-31 | 2013-08-15 | Towa Yakuhin Kk | Bitter-masked oral solution of quinolone-based antimicrobial agent |
| CN110141550A (en) * | 2019-07-09 | 2019-08-20 | 武汉兴华智慧医药科技有限公司 | A kind of lavo-ofloxacin oral administration solution and preparation method thereof |
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| JP5009707B2 (en) | 2012-08-22 |
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