JP3424038B2 - Synthetic antimicrobial agent aqueous composition - Google Patents
Synthetic antimicrobial agent aqueous compositionInfo
- Publication number
- JP3424038B2 JP3424038B2 JP15578596A JP15578596A JP3424038B2 JP 3424038 B2 JP3424038 B2 JP 3424038B2 JP 15578596 A JP15578596 A JP 15578596A JP 15578596 A JP15578596 A JP 15578596A JP 3424038 B2 JP3424038 B2 JP 3424038B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- atom
- carbon atoms
- amino
- halogen atom
- 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.)
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- 239000000203 mixture Substances 0.000 title claims description 14
- 239000004599 antimicrobial Substances 0.000 title 1
- YSLIPUSJNFIFAB-UHFFFAOYSA-N 2-oxopyridine-1-carboxylic acid Chemical compound OC(=O)N1C=CC=CC1=O YSLIPUSJNFIFAB-UHFFFAOYSA-N 0.000 claims description 30
- -1 1-piperazinyl group Chemical group 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 235000002639 sodium chloride Nutrition 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 15
- 239000003242 anti bacterial agent Substances 0.000 claims description 10
- 230000000844 anti-bacterial effect Effects 0.000 claims description 10
- 159000000007 calcium salts Chemical class 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 235000011187 glycerol Nutrition 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 8
- 239000004327 boric acid Substances 0.000 claims description 8
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 7
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 230000007928 solubilization Effects 0.000 claims description 6
- 238000005063 solubilization Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003889 eye drop Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 235000010338 boric acid Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 102220240796 rs553605556 Human genes 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 229960002713 calcium chloride Drugs 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 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 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960001180 norfloxacin Drugs 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 230000003381 solubilizing effect Effects 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 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 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- RXDLGFMMQFNVLI-UHFFFAOYSA-N [Na].[Na].[Ca] Chemical compound [Na].[Na].[Ca] RXDLGFMMQFNVLI-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000003899 bactericide agent Substances 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
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229940043430 calcium compound Drugs 0.000 description 1
- 150000001674 calcium compounds Chemical class 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 235000013927 calcium gluconate Nutrition 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
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 229960001229 ciprofloxacin hydrochloride Drugs 0.000 description 1
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 description 1
- ARPUHYJMCVWYCZ-UHFFFAOYSA-N ciprofloxacin hydrochloride hydrate Chemical compound O.Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ARPUHYJMCVWYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 239000000706 filtrate Substances 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 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 description 1
- 239000006228 supernatant Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 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
- 239000003643 water by type Substances 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【0001】[0001]
【発明の属する技術分野】本発明は、抗菌活性を有する
ピリドンカルボン酸及びその塩を含有する合成抗菌剤水
性組成物に関する。TECHNICAL FIELD The present invention relates to a synthetic antibacterial agent aqueous composition containing a pyridonecarboxylic acid having antibacterial activity and a salt thereof.
【0002】なお、ピリドンカルボン酸とは、3位にカ
ルボキシル基を、4位にオキソ基を有する1,4−ジヒ
ドロピリジンをその部分骨格として有する化合物で、下
記式で表されるものである。The pyridonecarboxylic acid is a compound having a carboxyl group at the 3-position and 1,4-dihydropyridine having an oxo group at the 4-position as its partial skeleton and is represented by the following formula.
【0003】[0003]
【化7】 [Chemical 7]
【0004】但し、式中、R1 :炭素数1〜5のアルキ
ル基、炭素数3〜6のシクロアルキル基、2,4−ジフ
ルオロフェニル基または2−フルオロエチル基、
R2 :水素原子、ハロゲン原子またはアミノ基、
R3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基・アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基、
A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、
R4 :水素原子または炭素数1〜5のアルキル基、
B:酸素原子または硫黄原子、
X:水素原子またはハロゲン原子、をそれぞれ示す。However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a 2,4-difluorophenyl group or a 2-fluoroethyl group, R 2 is a hydrogen atom, halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, an alkylamino group, an alkyl group having 1 to 5 carbon atoms, 1-piperazinyl group, 3
- methyl-1-piperazinyl, 4-methyl-1-piperazinyl group, or 3-amino-1-pyrrolidinyl group, A: what N, is hydrogen CH or CH substituted by a halogen atom, R 4: hydrogen An atom or an alkyl group having 1 to 5 carbon atoms, B: an oxygen atom or a sulfur atom, X: a hydrogen atom or a halogen atom, respectively.
【0005】[0005]
【従来の技術】ピリドンカルボン酸及びその塩は、グラ
ム陽性菌のみならずグラム陰性菌に対する極めて優れた
抗菌剤として広く知られている。BACKGROUND OF THE INVENTION Pyridonecarboxylic acid and its salts are widely known as extremely excellent antibacterial agents against not only Gram-positive bacteria but also Gram-negative bacteria.
【0006】一般的に、ピリドンカルボン酸は、中性域
での溶解性が乏しい。このため、中性域が要求される点
眼薬としては、本発明者らが知る限りにおいては、ピリ
ドンカルボン酸の内、オフロキサシンが上市されている
のみである。Generally, pyridonecarboxylic acid has poor solubility in the neutral range. Therefore, of the pyridonecarboxylic acids, ofloxacin is the only commercially available eye drop that requires a neutral range, as far as the present inventors know.
【0007】点眼薬は、pHをできるだけ、中性域に保
持して、眼粘膜組織への痛み・刺激を軽減することが必
要なためである。This is because it is necessary for eye drops to maintain the pH in the neutral range as much as possible to reduce pain and irritation to ocular mucosal tissues.
【0008】そこで、特開平2−121971号の公報
において、ピリドンカルボン酸に包含されるキノロンカ
ルボン酸の可溶化法として、水中で少なくとも等モル比
の水溶性カルシウム化合物と反応させ、そして、次に溶
液のpHを6.5〜7.5の間に調節して水溶液をえる
方法が提案されている。Therefore, in Japanese Patent Application Laid-Open No. 2-121971, a method for solubilizing a quinolonecarboxylic acid included in pyridonecarboxylic acid is to react with a water-soluble calcium compound in water at least at an equimolar ratio, and then It has been proposed to adjust the pH of the solution to a value between 6.5 and 7.5 to obtain an aqueous solution.
【0009】[0009]
【発明が解決しようとする課題】しかし、上記方法の場
合、ピリドンカルボン酸またはその塩の溶解度は十分と
は言えない(特開平4−59726号公報第2頁上右欄
参照)。However, in the case of the above method, the solubility of pyridonecarboxylic acid or a salt thereof is not sufficient (see JP-A-4-59726, page 2, upper right column).
【0010】このため、同公報においてピリドンカルボ
ン酸またはその塩に塩基性物質またはカルシウム塩を添
加して可溶化する方法が提案されている。Therefore, in this publication, a method of solubilizing a pyridonecarboxylic acid or its salt by adding a basic substance or a calcium salt is proposed.
【0011】ところが、上記方法の場合、塩基性物質を
使用するため調製液(水溶液)がアルカリ側にシフトす
る。同公報では塩化カルシウム液がpH6.5〜6.7
であるのに対し、本実施例では、pH9.0〜9.3で
ある(表1参照)。However, in the case of the above method, since the basic substance is used, the preparation liquid (aqueous solution) shifts to the alkaline side. In the publication, the calcium chloride solution has a pH of 6.5 to 6.7.
On the other hand, in this example, the pH is 9.0 to 9.3 (see Table 1).
【0012】このため、そのまま点眼薬等として使用す
ることはできず、中性域における溶解度は十分とはいえ
なかった。Therefore, it cannot be used as an eye drop as it is, and the solubility in the neutral range was not sufficient.
【0013】本発明は、上記にかんがみて、ピリドンカ
ルボン酸またはその塩の溶解度を増大させることができ
るとともに、中性域の水溶液を直接得ることができる合
成抗菌剤水性組成物を提供することを目的とする。In view of the above, the present invention provides a synthetic antibacterial agent aqueous composition capable of increasing the solubility of pyridonecarboxylic acid or a salt thereof and directly obtaining an aqueous solution in a neutral range. To aim.
【0014】[0014]
【課題を解決するための手段】本発明の合成抗菌剤水性
組成物は、下記構成により上記課題を解決するものであ
る。The synthetic antibacterial agent aqueous composition of the present invention solves the above problems by the following constitution.
【0015】両性化合物であって、抗菌活性を有し下記
一般式で表されるピリドンカルボン酸またはその塩に、
塩化カルシウム及びポリビニルピロリドンが添加され
て、pH6.0〜8.5に調整されてなることを特徴と
する。An amphoteric compound, which has an antibacterial activity and is represented by the following general formula, pyridonecarboxylic acid or a salt thereof,
It is characterized in that the pH is adjusted to 6.0 to 8.5 by adding calcium chloride and polyvinyl pyrrolidone.
【0016】[0016]
(1) ピリドンカルボン酸としては、前記一般式で表され
るものを使用できるが、点眼薬用としては、具体的には
下記のものを例示できる。(1) As the pyridonecarboxylic acid, those represented by the above general formula can be used, and specifically for the eye drops, the following can be exemplified.
【0017】キノリン骨格を有するものとしては、
1−エチル−6−フルオロ−1,4−ジヒドロ−4−オ
キソ−7−(1−ピペラジニル)−3−キノリンカルボ
ン酸(一般名:ノルフロキサシン)
1−シクロプロピル−6−フルオロ−1,4−ジヒドロ
−4−オキソ−7−(1−ピペラジニル)−3−キノリ
ンカルボン酸塩酸塩水和物(一般名:塩酸シプロフロキ
サシン)
5−アミノ−1−シクロプロピル−7−(シス−3,5
−ジメチル−1−ピペラジニル)−6,8−ジフルオロ
−1,4−ジヒドロ−4−オキソ−3−キノリンカルボ
ン酸(一般名:スパフロキサシン)
1,8−ナフチリジン骨格を有するものとしては、
(±)−7−(3−アミノ−1−ピロリジニル)−6−
フルオロ−1−(2,4−ジフルオロフェニル)−1,
4−ジヒドロ−4−オキソ−1,8−ナフチリジン−3
−カルボン酸パラトルエンスルフォネート水和物(一般
名:トシル酸トスフロキサシン)
ピリドンカルボン酸の塩としては、通常、知られている
アミノ基などの塩基性基またはカルボキシル基などの酸
性基における塩を挙げることができる。塩基性基におけ
る塩としては、例えば、塩酸、硫酸若しくはリン酸等の
無機酸との塩;酢酸、乳酸、コハク酸、メタンスルホン
酸、p−トルエンスルホン酸、マレイン酸、マロン酸若
しくはグルコン酸との有機酸との塩、またはアスパラギ
ン酸若しくはグルタミン酸などのアミノ酸との塩など
を、また、酸性基における塩としては、例えば、ナトリ
ウム若しくはカリウムなどのアルカリ金属との塩などを
挙げることができる(前述の特開平4−59726号公
報第3頁下段参照)。As those having a quinoline skeleton, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid (general name: norfloxacin) 1- Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid hydrochloride hydrate (generic name: ciprofloxacin hydrochloride) 5-amino-1- Cyclopropyl-7- (cis-3,5
-Dimethyl-1-piperazinyl) -6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (generic name: spafloxacin) As having a 1,8-naphthyridine skeleton, (±) -7- (3-amino-1-pyrrolidinyl) -6-
Fluoro-1- (2,4-difluorophenyl) -1,
4-dihydro-4-oxo-1,8-naphthyridine-3
-Carboxylic acid paratoluene sulfonate hydrate (generic name: tosfloxacin tosylate) As a salt of pyridonecarboxylic acid, a salt in a known basic group such as amino group or an acidic group such as carboxyl group is usually used. Can be mentioned. Examples of the salt in the basic group include salts with inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid; acetic acid, lactic acid, succinic acid, methanesulfonic acid, p-toluenesulfonic acid, maleic acid, malonic acid or gluconic acid. With an organic acid, or a salt with an amino acid such as aspartic acid or glutamic acid, and examples of the salt in the acidic group include salts with an alkali metal such as sodium or potassium (the above-mentioned. JP-A-4-59726, page 3, lower part).
【0018】(2) カルシウム塩としては、塩化カルシウ
ム、乳酸カルシウム、パントテン酸カルシウム、グルコ
ン酸カルシウム、炭酸カルシウム、D−糖酸カルシウ
ム、エデト酸二ナトリウムカルシウム等を挙げることが
できるが、これらの内で塩化カルシウムが特に望まし
い。カルシウム塩の添加量は、ピリドンカルボン酸に対
して、0.5〜4倍量(望ましくは、1〜3倍量)とす
る。過少では、本発明の効果(ピリドンカルボン酸の可
溶化)を奏し難く、過多では、点眼薬として使用した場
合、眼粘膜障害の副作用が生じる可能性がある。(2) Examples of calcium salts include calcium chloride, calcium lactate, calcium pantothenate, calcium gluconate, calcium carbonate, calcium D-sugarate, and disodium calcium edetate. Therefore, calcium chloride is particularly desirable. The amount of calcium salt added is 0.5 to 4 times (preferably 1 to 3 times) the amount of pyridonecarboxylic acid. When the amount is too small, the effect of the present invention (solubilization of pyridonecarboxylic acid) is difficult to be achieved, and when the amount is too large, it may cause a side effect of ocular mucosal damage when used as an eye drop.
【0019】(3) ポリビニルピロリドン(PVP)とし
ては、「PVP K−25」(平均分子量2万5千)、
「PVP K−30」(平均分子量4万)、「PVP
K−90」(平均分子量36万)等を、好適に使用可能
である。PVPの添加量は、ピリドンカルボン酸に対し
て、3〜20倍量(望ましくは、6〜15倍量)とす
る。過少では、本発明の効果(ピリドンカルボン酸の可
溶化)を奏し難く、過多では、粘性が増し点眼薬として
使用した場合、爽快感を阻害する可能性がある。(3) As polyvinylpyrrolidone (PVP), "PVP K-25" (average molecular weight 25,000),
"PVP K-30" (average molecular weight 40,000), "PVP
K-90 "(average molecular weight 360,000) and the like can be preferably used. The amount of PVP added is 3 to 20 times (preferably 6 to 15 times) the amount of pyridonecarboxylic acid. If the amount is too small, the effect of the present invention (solubilization of pyridonecarboxylic acid) is difficult to be exhibited, and if the amount is too large, the viscosity is increased and the refreshing feeling may be hindered when used as an eye drop.
【0020】(4) 上記において、ピリドンカルボン酸の
可溶化を、更に促進するために、グリセリン又はホウ酸
を、添加することが望ましい。(4) In the above, in order to further promote the solubilization of pyridonecarboxylic acid, it is desirable to add glycerin or boric acid.
【0021】グリセリンの添加量は、ピリドンカルボン
酸に対して、3〜10倍量(望ましくは、4〜7倍量)
とする。過少では、本発明の効果(ピリドンカルボン酸
の可溶化促進)を奏し難く、過多では、点眼薬として使
用した場合、浸透圧の上昇により爽快感を阻害する可能
性がある。The amount of glycerin added is 3 to 10 times (preferably 4 to 7 times) the amount of pyridonecarboxylic acid.
And If the amount is too small, the effect of the present invention (promoting solubilization of pyridonecarboxylic acid) is difficult to be exhibited, and if the amount is too large, when used as an eye drop, there is a possibility that the refreshing feeling may be hindered due to an increase in osmotic pressure.
【0022】ホウ酸の添加量は、ピリドンカルボン酸に
対して、1〜5倍量(望ましくは、2〜4倍量)とす
る。過少では、本発明の効果(ピリドンカルボン酸の可
溶化促進)を奏し難く、過多では、点眼薬として使用し
た場合、浸透圧の上昇により爽快感を阻害する可能性が
あるとともに、過敏症状が出てくる可能性がある。The amount of boric acid added is 1 to 5 times (preferably 2 to 4 times) the amount of pyridonecarboxylic acid. If the amount is too small, the effect of the present invention (promoting solubilization of pyridonecarboxylic acid) is difficult to be exerted, and if too much, when used as an eye drop, it may inhibit refreshing feeling due to increase in osmotic pressure, and hypersensitivity symptoms appear There is a possibility of coming.
【0023】(5) 上記ピリドンカルボン酸に塩化カルシ
ウム塩、PVPさらにはグリセリン又はホウ酸、必要に
より防腐剤(殺菌剤)を添加した混合物を、滅菌精製水
で加温溶解させ、フィルターでろ過して本願発明の水性
組成物を調製する。(5) A mixture prepared by adding calcium chloride salt, PVP, glycerin or boric acid, and optionally a preservative (bactericide) to the above pyridonecarboxylic acid is dissolved by heating with sterilized purified water and filtered with a filter. To prepare the aqueous composition of the present invention.
【0024】[0024]
【発明の効果】 本発明の合成抗菌剤水性組成物は、ピ
リドンカルボン酸またはその塩に、カルシウム塩、ポリ
ビニルピロリドンに加えて、グリセリン及び/又はホウ
酸を添加することにより、pH6.0〜8.5に調整さ
れてなる構成により下記のような効果を奏する。EFFECTS OF THE INVENTION The synthetic antibacterial agent aqueous composition of the present invention contains pyridonecarboxylic acid or a salt thereof , in addition to calcium salt , polyvinylpyrrolidone , glycerin and / or borate.
By adding an acid, the following effects can be achieved by the constitution in which the pH is adjusted to 6.0 to 8.5.
【0025】後述の試験例・実施例で支持される如く、
ピリドンカルボン酸又はその塩の溶解度を増大させるこ
とができるとともに、中性域の水溶液が直接得ることが
できる。As supported by the test examples and examples described below,
The solubility of pyridonecarboxylic acid or its salt can be increased, and an aqueous solution in a neutral region can be directly obtained.
【0026】[0026]
【0027】[0027]
(1) 表1の組成の混合物に、滅菌精製水80mLを添加
し、加温溶解し、滅菌精製水を加えて100mLとし
た。次に、0.22μmのメンブランフィルターでろ過
した後、点眼容器に充填し、化合物A0.3W/V %の各
点眼液を調製した。(1) To the mixture having the composition shown in Table 1, 80 mL of sterilized purified water was added, dissolved by heating, and sterilized purified water was added to make 100 mL. Next, the solution was filtered through a 0.22 μm membrane filter and then filled in an eye drop container to prepare each eye drop solution of Compound A 0.3 W / V%.
【0028】各実施例の pH 及び浸透圧を表1に示す。
表1に示す結果から、いずれの点眼薬も中性域のもので
あることがわかる。Table 1 shows the pH and osmotic pressure of each example.
From the results shown in Table 1, it can be seen that all the eye drops are in the neutral range.
【0029】(2) 各試料溶液20mLに、溶けなくなる
までノルフロキサシンを加え、60°、30分間加温さ
せた後室温にて24時間放置し、4000rpm、30
分間遠心分離させ、上澄み液を0.22μmメンブラン
フィルターろ過し、ろ液を高速液体クロマトグラフィー
(Waters486)にて溶解度を測定した。(2) Norfloxacin was added to 20 mL of each sample solution until it became insoluble, heated at 60 ° for 30 minutes, and then allowed to stand at room temperature for 24 hours, 4000 rpm, 30
After centrifuging, the supernatant was filtered with a 0.22 μm membrane filter and the solubility of the filtrate was measured by high performance liquid chromatography (Waters 486).
【0030】試験結果及びそれから計算した溶解度比
(試料溶液/水)を表2に示すが、カルシウム塩/PV
P併用系は、各化合物単独よりピリドンカルボン酸の溶
解度が増大している。更に、それらに、グリセリンまた
はホウ酸を併用した場合は、格段に溶解度が増大するこ
とがわかる。The test results and the solubility ratios (sample solution / water) calculated from them are shown in Table 2.
The P combination system has a higher solubility of pyridonecarboxylic acid than each compound alone. Furthermore, it can be seen that the solubility is remarkably increased when glycerin or boric acid is used in combination with them.
【0031】[0031]
【表1】 [Table 1]
【0032】[0032]
【表2】 [Table 2]
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI A61K 47/32 A61K 47/32 A61P 27/02 A61P 27/02 31/04 31/04 C07D 215/56 C07D 215/56 401/04 401/04 471/04 114 471/04 114Z 498/06 498/06 513/06 513/06 (56)参考文献 特開 平2−121917(JP,A) 特開 昭63−264418(JP,A) 特開 昭63−174930(JP,A) (58)調査した分野(Int.Cl.7,DB名) A61K 31/47 A61K 9/08 A61K 31/435 A61K 31/495 A61K 31/535 A61K 31/54 A61K 31/55 A61K 47/02 A61K 47/10 A61K 47/32 A61P 31/04 A61P 27/02 C07D 215/56 C07D 401/04 C07D 471/04 C07D 498/06 C07D 513/06 CAPLUS(STN) REGISTRY(STN) MEDLINE(STN) EMBASE(STN)─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 7 Identification code FI A61K 47/32 A61K 47/32 A61P 27/02 A61P 27/02 31/04 31/04 C07D 215/56 C07D 215/56 401 / 04 401/04 471/04 114 471/04 114Z 498/06 498/06 513/06 513/06 (56) Reference JP-A-2-121917 (JP, A) JP-A-63-264418 (JP, A ) JP-A-63-174930 (JP, A) (58) Fields investigated (Int.Cl. 7 , DB name) A61K 31/47 A61K 9/08 A61K 31/435 A61K 31/495 A61K 31/535 A61K 31 / 54 A61K 31/55 A61K 47/02 A61K 47/10 A61K 47/32 A61P 31/04 A61P 27/02 C07D 215/56 C07D 401/04 C07D 471/04 C07D 498/06 C07D 513/06 CAPLUS (STN) REGISTRY (STN) MEDLINE (STN) EMBASE (STN)
Claims (6)
記一般式で表されるピリドンカルボン酸またはその塩に
対して、それらの可溶化促進剤としてカルシウム塩、ポ
リビニルピロリドン及びグリセリンが添加されて、pH
6.0〜8.5に調整されてなることを特徴とする合成
抗菌剤水性組成物。 【化1】 但し、式中、R1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R2 :水素原子、ハロゲン原子またはアミノ基、 R3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基、 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。1. A pyridonecarboxylic acid represented by the following general formula or a salt thereof which is an amphoteric compound and has antibacterial activity.
On the other hand, calcium salts , polyvinylpyrrolidone and glycerin were added as solubilization promoters to increase pH.
A synthetic antibacterial agent aqueous composition characterized by being adjusted to 6.0 to 8.5. [Chemical 1] However, in the formula, R 1 : an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a 2,4-difluorophenyl group or a 2-fluoroethyl group, R 2 : a hydrogen atom, a halogen atom or amino group, R 3: an amino group, an aminoalkyl group, an alkylamino group having 1 to 5 carbon atoms, an alkyl group, 1-piperazinyl group, 3
- methyl-1-piperazinyl, 4-methyl-1-piperazinyl group, or 3-amino-1-pyrrolidinyl group, A: what N, is hydrogen CH or CH substituted by a halogen atom, R 4: hydrogen An atom or an alkyl group having 1 to 5 carbon atoms, B: an oxygen atom or a sulfur atom, X: a hydrogen atom or a halogen atom, respectively.
記一般式で表されるピリドンカルボン酸またはその塩に
対して、カルシウム塩:0.5〜4倍量、ポリビニルピ
ロリドン:3〜20倍量及びグリセリン:3〜10倍量
が添加されて、pH6.0〜8.5に調整されてなるこ
とを特徴とする合成抗菌剤水性組成物。 【化2】 但し、式中、R 1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R 2 :水素原子、ハロゲン原子またはアミノ基、 R 3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基、 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R 4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。 2. An amphoteric compound, which has antibacterial activity
The pyridonecarboxylic acid represented by the general formula or its salt
On the other hand, calcium salt: 0.5 to 4 times amount, polyvinylpyrrole
Loridone: 3 to 20 times amount and glycerin: 3 to 10 times amount
Is added to adjust the pH to 6.0-8.5.
A synthetic antibacterial agent aqueous composition comprising: [Chemical 2] However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms,
3-6 cycloalkyl groups, 2,4-difluorophenyl
Le group or a 2-fluoroethyl group, R 2: a hydrogen atom, a halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, A 1 to 5 carbon atoms
Rukylamino group, alkyl group, 1-piperazinyl group, 3
-Methyl-1-piperazinyl group, 4-methyl-1-pipet
Razinyl group or 3-amino-1-pyrrolidinyl
Group, A: hydrogen of N, CH or CH is replaced by a halogen atom.
And R 4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, B is an oxygen atom or a sulfur atom, and X is a hydrogen atom or a halogen atom.
記一般式で表されるピリドンカルボン酸またはその塩に
対して、それらの可溶化促進剤としてカルシウム塩、ポ
リビニルピロリドン及びホウ酸が添加されて、pH6.
0〜8.5に調整されてなることを特徴とする合成抗菌
剤水性組成物。 【化3】 但し、式中、R 1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R 2 :水素原子、ハロゲン原子またはアミノ基、 R 3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基。 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R 4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。 3. An amphoteric compound having antibacterial activity
The pyridonecarboxylic acid represented by the general formula or its salt
On the other hand, calcium salts and
Rivinylpyrrolidone and boric acid were added to give a pH of 6.
Synthetic antibacterial characterized by being adjusted to 0 to 8.5
Aqueous composition. [Chemical 3] However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms,
3-6 cycloalkyl groups, 2,4-difluorophenyl
Le group or a 2-fluoroethyl group, R 2: a hydrogen atom, a halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, A 1 to 5 carbon atoms
Rukylamino group, alkyl group, 1-piperazinyl group, 3
-Methyl-1-piperazinyl group, 4-methyl-1-pipet
Razinyl group or 3-amino-1-pyrrolidinyl
Basis. A: N, CH or CH hydrogen is replaced by a halogen atom.
And R 4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, B is an oxygen atom or a sulfur atom, and X is a hydrogen atom or a halogen atom.
記一般式で表されるピリドンカルボン酸またはその塩に
対して、カルシウム塩:0.5〜4倍量、ポリビニルピ
ロリドン:3〜20倍量及びホウ酸:1〜5倍量が添加
されて、pH6.0〜8.5に調整されてなることを特
徴とする合成抗菌剤水性組成物。 【化4】 但し、式中、R 1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R 2 :水素原子、ハロゲン原子またはアミノ基、 R 3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基。 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R 4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。 4. An amphoteric compound having antibacterial activity
The pyridonecarboxylic acid represented by the general formula or its salt
On the other hand, calcium salt: 0.5 to 4 times amount, polyvinylpyrrole
Loridone: 3 to 20 times amount and boric acid: 1 to 5 times amount added
The pH is adjusted to 6.0-8.5.
A synthetic antibacterial agent aqueous composition. [Chemical 4] However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms,
3-6 cycloalkyl groups, 2,4-difluorophenyl
Le group or a 2-fluoroethyl group, R 2: a hydrogen atom, a halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, A 1 to 5 carbon atoms
Rukylamino group, alkyl group, 1-piperazinyl group, 3
-Methyl-1-piperazinyl group, 4-methyl-1-pipet
Razinyl group or 3-amino-1-pyrrolidinyl
Basis. A: N, CH or CH hydrogen is replaced by a halogen atom.
And R 4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, B is an oxygen atom or a sulfur atom, and X is a hydrogen atom or a halogen atom.
記一般式で表されるピリドンカルボン酸またはその塩に
対して、それらの可溶化促進剤としてカルシウム塩、ポ
リビニルピロリドン、グリセリン及びホウ酸が添加され
て、pH6.0〜8.5に調整されてなることを特徴と
する合成抗菌剤水性組成物。 【化5】 但し、式中、R 1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R 2 :水素原子、ハロゲン原子またはアミノ基、 R 3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基、 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R 4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。 5. An amphoteric compound having an antibacterial activity
The pyridonecarboxylic acid represented by the general formula or its salt
On the other hand, calcium salts and
Rivinylpyrrolidone, glycerin and boric acid are added
And pH is adjusted to 6.0 to 8.5.
A synthetic antibacterial agent aqueous composition. [Chemical 5] However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms,
3-6 cycloalkyl groups, 2,4-difluorophenyl
Le group or a 2-fluoroethyl group, R 2: a hydrogen atom, a halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, A 1 to 5 carbon atoms
Rukylamino group, alkyl group, 1-piperazinyl group, 3
-Methyl-1-piperazinyl group, 4-methyl-1-pipet
Razinyl group or 3-amino-1-pyrrolidinyl
Group, A: hydrogen of N, CH or CH is replaced by a halogen atom.
And R 4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, B is an oxygen atom or a sulfur atom, and X is a hydrogen atom or a halogen atom.
記一般式で表されるピリドンカルボン酸またはその塩に
対して、カルシウム塩:0.5〜4倍量、ポリビニルピ
ロリドン:3〜20倍量、グリセリン:3〜10倍量及
びホウ酸:1〜5倍量が添加されて、pH6.0〜8.
5に調整されてなることを特徴とする合成抗菌剤水性組
成物。 【化6】 但し、式中、R 1 :炭素数1〜5のアルキル基、炭素数
3〜6のシクロアルキル基、2,4−ジフルオロフェニ
ル基または2−フルオロエチル基、 R 2 :水素原子、ハロゲン原子またはアミノ基、 R 3 :アミノ基、炭素数1〜5のアミノアルキル基・ア
ルキルアミノ基、アルキル基、1−ピペラジニル基、3
−メチル−1−ピペラジニル基、4−メチル−1−ピペ
ラジニル基、または、3−アミノ−1−ピロリジニル
基、 A:N、CHまたはCHの水素がハロゲン原子で置換さ
れたもの、 R 4 :水素原子または炭素数1〜5のアルキル基、 B:酸素原子または硫黄原子、 X:水素原子またはハロゲン原子、をそれぞれ示す。 6. An amphoteric compound having antibacterial activity
The pyridonecarboxylic acid represented by the general formula or its salt
On the other hand, calcium salt: 0.5 to 4 times amount, polyvinylpyrrole
Loridone: 3 to 20 times amount, glycerin: 3 to 10 times amount
Biboric acid: 1 to 5 times the amount of boric acid is added to give a pH of 6.0 to 8.
Synthetic antibacterial agent aqueous set characterized by being adjusted to 5
A product. [Chemical 6] However, in the formula, R 1 is an alkyl group having 1 to 5 carbon atoms,
3-6 cycloalkyl groups, 2,4-difluorophenyl
Le group or a 2-fluoroethyl group, R 2: a hydrogen atom, a halogen atom or an amino group, R 3: an amino group, an aminoalkyl group, A 1 to 5 carbon atoms
Rukylamino group, alkyl group, 1-piperazinyl group, 3
-Methyl-1-piperazinyl group, 4-methyl-1-pipet
Razinyl group or 3-amino-1-pyrrolidinyl
Group, A: hydrogen of N, CH or CH is replaced by a halogen atom.
And R 4 is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, B is an oxygen atom or a sulfur atom, and X is a hydrogen atom or a halogen atom.
Priority Applications (1)
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JP15578596A JP3424038B2 (en) | 1996-06-17 | 1996-06-17 | Synthetic antimicrobial agent aqueous composition |
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JP15578596A JP3424038B2 (en) | 1996-06-17 | 1996-06-17 | Synthetic antimicrobial agent aqueous composition |
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JPH107568A JPH107568A (en) | 1998-01-13 |
JP3424038B2 true JP3424038B2 (en) | 2003-07-07 |
Family
ID=15613374
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JP15578596A Expired - Fee Related JP3424038B2 (en) | 1996-06-17 | 1996-06-17 | Synthetic antimicrobial agent aqueous composition |
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JP2002037746A (en) * | 2000-07-24 | 2002-02-06 | Fuji Yakuhin:Kk | Liquid preparation containing quinolonecarboxylic acid based antimicrobial agent |
CN100337630C (en) * | 2002-03-12 | 2007-09-19 | 布里斯托尔-迈尔斯斯奎布公司 | Palatable oral suspension and method |
JP2005008625A (en) * | 2003-05-23 | 2005-01-13 | Santen Pharmaceut Co Ltd | Eye lotion containing quinolone-based antibacterial compound |
MX2010010686A (en) | 2008-03-31 | 2011-02-23 | Kyorin Seiyaku Kk | Aqueous liquid containing gatifloxacin, method for production thereof, and method for prevention of production of precipitates during storage of the aqueous liquid at low temperature or upon freezing/thawing of the aqueous liquid. |
CA2805656A1 (en) * | 2010-07-21 | 2012-01-26 | Alcon Research, Ltd. | Pharmaceutical composition with enhanced solubility characteristics |
JP2013129618A (en) * | 2011-12-21 | 2013-07-04 | Nippon Tenganyaku Kenkyusho:Kk | Levofloxacin-containing water liquid medicine that improves antiseptic efficacy and physical properties |
AR093458A1 (en) | 2012-11-12 | 2015-06-10 | Southwire Co | A WIRE AND CABLE PACK |
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