JPS6333327A - Stabilized phenylephrine liquid agent - Google Patents
Stabilized phenylephrine liquid agentInfo
- Publication number
- JPS6333327A JPS6333327A JP17717286A JP17717286A JPS6333327A JP S6333327 A JPS6333327 A JP S6333327A JP 17717286 A JP17717286 A JP 17717286A JP 17717286 A JP17717286 A JP 17717286A JP S6333327 A JPS6333327 A JP S6333327A
- Authority
- JP
- Japan
- Prior art keywords
- phenylephrine
- liquid agent
- agent
- salt
- useful
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960001802 phenylephrine Drugs 0.000 title claims abstract description 19
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 title claims abstract description 16
- 239000007788 liquid Substances 0.000 title claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 239000004334 sorbic acid Substances 0.000 claims abstract description 11
- 229940075582 sorbic acid Drugs 0.000 claims abstract description 11
- 235000010199 sorbic acid Nutrition 0.000 claims abstract description 11
- 150000001413 amino acids Chemical class 0.000 claims abstract description 10
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 abstract description 10
- -1 sorbic acid compound Chemical class 0.000 abstract description 10
- 239000003889 eye drop Substances 0.000 abstract description 9
- 238000002845 discoloration Methods 0.000 abstract description 7
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 abstract description 6
- 229940068988 potassium aspartate Drugs 0.000 abstract description 6
- 239000011521 glass Substances 0.000 abstract description 4
- 239000007923 nasal drop Substances 0.000 abstract description 4
- 239000003381 stabilizer Substances 0.000 abstract description 4
- 230000002911 mydriatic effect Effects 0.000 abstract description 3
- 229920003023 plastic Polymers 0.000 abstract description 3
- 239000004033 plastic Substances 0.000 abstract description 3
- 230000032683 aging Effects 0.000 abstract 1
- 230000002542 deteriorative effect Effects 0.000 abstract 1
- 230000004060 metabolic process Effects 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229940012356 eye drops Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004040 coloring Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229940100662 nasal drops Drugs 0.000 description 3
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 2
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930003451 Vitamin B1 Natural products 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 229960001983 magnesium aspartate Drugs 0.000 description 2
- OSZNNLWOYWAHSS-UHFFFAOYSA-M neostigmine methyl sulfate Chemical compound COS([O-])(=O)=O.CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 OSZNNLWOYWAHSS-UHFFFAOYSA-M 0.000 description 2
- 229960002253 neostigmine methylsulfate Drugs 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000010374 vitamin B1 Nutrition 0.000 description 2
- 239000011691 vitamin B1 Substances 0.000 description 2
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 1
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔技術分野〕
本発明は、点眼液あるいは点鼻液として有用な安定化さ
れたフェニレフリン系液剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to stabilized phenylephrine solutions useful as eye drops or nasal drops.
フェニレフリン系化合物は、強力な血管収縮作用および
散瞳作用を有することから、点眼液あるいは点鼻液とし
て繁用されている。Phenylephrine compounds have strong vasoconstrictor and mydriatic effects, and are therefore frequently used as eye drops or nasal drops.
このフェニレフリン系化合物の力価は中性ないし弱酸性
で安定であるが、この水溶液は長時間保存すると不安定
になり溶液が着色又は変色するという欠点があり、特に
新陳代射促進剤や抗プラスミン剤としてアスパラギン酸
カリウム等のアミノ酸あるいはアミノ酸塩が配合された
水溶液の場合は、その着色又は変色劣化が著しい。The potency of this phenylephrine compound is neutral to weakly acidic and stable, but this aqueous solution has the disadvantage that it becomes unstable and becomes colored or discolored when stored for a long time. In the case of an aqueous solution containing an amino acid or an amino acid salt such as potassium aspartate as a plasmin agent, the discoloration or discoloration of the solution is significant.
従来、このようなフェニレフリン系化合物の安定化方法
としては、ｐＨを１付近に保つ方法、酸素を遮断する方
法、エデト酸塩根のキレート試薬を添加する方法あるい
はメタ重亜硫酸塩等の抗酸化剤を添加する方法の種々の
方法が提案されているが、いずれも満足すべきものでは
なかった。Conventionally, methods for stabilizing such phenylephrine compounds include keeping the pH around 1, blocking oxygen, adding edetate radical chelating reagents, or adding antioxidants such as metabisulfite. Various methods have been proposed for adding , but none of them have been satisfactory.
例えば、ｐＨが１付近に保たれたフェニレフリン系点眼
液あるいは点鼻液は、生体に使用した場合の刺激性に問
題があり、また他の方法も着色又は変色防止効果が不充
分でありその商品価値が劣るものであった。For example, phenylephrine-based eye drops or nasal drops whose pH is kept around 1 have a problem with irritation when used on living organisms, and other methods also have insufficient effects on preventing coloring or discoloration, and the product It was of lesser value.
本発明は、経日あるいは日光曝露によっても着色又は変
色を生じることがなく、しかも使用感に優れたフェニレ
フリン系液剤を提供することを目的とする。An object of the present invention is to provide a phenylephrine-based liquid preparation that does not become colored or discolored over time or when exposed to sunlight and has an excellent feel when used.
本発明によれば、フェニレフリン系化合物及びアミノ酸
もしくはその塩を配合した液剤であって、更にソルビン
酸又はその塩をｏ、ｏｏｓ〜０．ＩＶ／Ｖ％含有させた
ことを特徴とする安定化されたフェニレフリン系液剤が
提供される。According to the present invention, there is provided a liquid preparation containing a phenylephrine compound and an amino acid or a salt thereof, further containing sorbic acid or a salt thereof at o, oos to 0. A stabilized phenylephrine solution is provided, characterized in that it contains IV/V%.
本発明のフェニレフリン液剤は、安定化剤としてソルビ
ン酸又はその塩をｏ、ｏｏｓ〜０．ＩＶ／Ｖ％含有させ
たことから、アミノ酸もしくはその塩が配合されている
にも拘らず、経日によっても安定であり、また長期間日
光等に曝露されても着色又は変色を生じることがないた
め、プラスチック容器やガラス容器に入れて保存するこ
とができ、しかもその保存Ｐｌ＋も通常の点眼剤として
好ましい値である５以上にすることが可能であるため、
その使用感にも優れたものである。The phenylephrine solution of the present invention contains sorbic acid or its salt as a stabilizer at o, oos to 0. Because it contains IV/V%, it is stable over time even though it contains amino acids or its salts, and does not become colored or discolored even if exposed to sunlight for a long period of time. Therefore, it can be stored in a plastic or glass container, and its storage Pl+ can be 5 or more, which is a preferable value for ordinary eye drops.
It also has an excellent usability.
つぎに、本発明をさらに詳細に説明する。Next, the present invention will be explained in more detail.
本発明は、安定化剤としてソルビン酸又はその塩を用い
る。The present invention uses sorbic acid or a salt thereof as a stabilizer.
ソルビン酸の塩としては、ナトリウム、カリウム等のア
ルカリ金属塩が好ましく用いられる。ソルビン酸又はそ
の塩の配合ヱは全液剤溶量に対し、ｏ、ｏｏｓ 〜ｏ、
１ｗハぶ、好ましくは０．０１〜０．０５Ｗ／Ｖ％であ
る。ソルビン酸の配合量が、０．ＩＷ／Ｖ％を超えると
粘膜刺激作用が強過ぎ、点眼剤への応用に雑煮を生じ、
またソルビン酸塩の配分量が０．１Ｖ／Ｖ％を超えると
、液剤の安定性が逆に悪くなる。また０、００５Ｗ／Ｖ
％未満では着色又は変色防止効果が不充分となる。As the salt of sorbic acid, alkali metal salts such as sodium and potassium are preferably used. The formulation of sorbic acid or its salt is o, oos to o, based on the total liquid solution amount.
1w hub, preferably 0.01 to 0.05 W/V%. If the blending amount of sorbic acid is 0. If it exceeds IW/V%, the mucous membrane irritation effect is too strong, causing problems when applied to eye drops.
Furthermore, if the amount of sorbate to be distributed exceeds 0.1 V/V%, the stability of the solution will deteriorate. Also 0,005W/V
If it is less than %, the effect of preventing coloring or discoloration will be insufficient.
本発明で用いるフェニレフリン系化合物は、下記一般式
で表わされるフェニレフリンの他その無機塩又は有機塩
が包含される。The phenylephrine compounds used in the present invention include phenylephrine represented by the following general formula and other inorganic or organic salts.
無機塩としては、塩酸塩、リン酸塩、硫酸塩、硝酸塩が
挙げられるが、塩酸塩が好ましく用いられる。Examples of the inorganic salt include hydrochloride, phosphate, sulfate, and nitrate, and hydrochloride is preferably used.
有機塩としては、酒石酸塩、タンニン酸塩、クエン酸塩
、サリチル酸塩、グルタミン酸塩が挙げられるが、酒石
酸を用いることが望ましい。Examples of organic salts include tartrates, tannates, citrates, salicylates, and glutamates, and tartaric acid is preferably used.
本発明においては、フェニレフリン系化合物の使用量は
全液剤溶量に対して、０．０１〜０．Ｈ１／Ｖ％。In the present invention, the amount of phenylephrine compound to be used is 0.01 to 0.01 to 0.01 to 0.01 to 0.01 to 0.01 to 0.01 to 0.01. H1/V%.
好ましくは０．０３〜０．０８１／Ｖ％である。 ０．
１１／Ｖ％を超えると、一般用薬として好ましくない散
瞳作用が出現することとなり、また０、０１１／Ｖ％未
満では効果が不充分となるので望ましくない。Preferably it is 0.03 to 0.081/V%. 0.
If it exceeds 11/V%, a mydriatic effect that is undesirable as a general medicine will appear, and if it is less than 0.011/V%, the effect will be insufficient, which is not desirable.
本発明においては、前記フェニレフリン系化合物と共に
新陳代射促、進剤あるいは抗プラスミン剤としてアミノ
酸もしくはその塩を用いる。アミノ酸もしくはその塩と
しては、例えばアスパラギン酸カリウム、アスパラギン
酸マグネシウム、アスパラギン酸マグネシウム・カリウ
ム、アミノエチルスルホン酸、ε−アミノカプロン酸が
例示されるが、有効性の点からみて、アスパラギン酸カ
リウムを用いることが適当である。アミノ酸もしくはそ
の塩の使用量は、全液剤溶量に対して、０．１〜５Ｗ／
Ｖ％、好ましくは０．５〜ＩＶ／Ｖ％である。５Ｖ／Ｖ
％を超えると、副作用が出現することとなり、０．１１
１１／Ｖ２未満では効果が不充分となるので望ましくな
い。In the present invention, an amino acid or a salt thereof is used together with the phenylephrine compound as an ejaculatory agent, stimulant, or anti-plasmin agent. Examples of the amino acid or its salt include potassium aspartate, magnesium aspartate, magnesium/potassium aspartate, aminoethylsulfonic acid, and ε-aminocaproic acid, but from the viewpoint of effectiveness, potassium aspartate is preferably used. is appropriate. The amount of amino acid or its salt to be used is 0.1 to 5 W/to the total amount of liquid solution.
V%, preferably 0.5 to IV/V%. 5V/V
If it exceeds 0.11%, side effects will occur.
If it is less than 11/V2, the effect will be insufficient, which is not desirable.
本発明においては、上記必須成分の他にこの種液剤に通
常使用されている補助成分、例えば、メチル硫酸ネオス
チグミン、抗ヒスタミン剤、抗炎症剤、ビタミン、緩衝
剤、等張化剤及び増粘剤等を配合することもできる。こ
の場合、抗ヒスタミン剤としては、マレイン酸クロルフ
ェニラミン、塩酸ジフェンヒドラミンが、抗炎症剤とし
ては、グリチルリチン酸二カリウム、グリチルレチン酸
が、ビタミンとしては、ビタミンＡ、ビタミンＢいビタ
ミン８いビタミンＢ１□、ビタミンＥが、緩衝剤として
は、ホウ酸、ホウ砂、クエン酸、クエン酸ナトリウムを
挙げることができる。また、等張化剤としては、塩化カ
リウム、塩化カルシウム、塩化ナトリウムが、増粘剤と
しては、コンドロイチン硫酸ナトリウム、ポリビニルア
ルコール、ポリビニルピロリドン、ヒドロキシエチルセ
ルロースが例示される。In addition to the above-mentioned essential ingredients, the present invention contains auxiliary ingredients commonly used in this type of liquid preparations, such as neostigmine methyl sulfate, antihistamines, anti-inflammatory agents, vitamins, buffering agents, tonicity agents, and thickening agents. It can also be blended. In this case, the antihistamines are chlorpheniramine maleate and diphenhydramine hydrochloride, the anti-inflammatory agents are dipotassium glycyrrhizinate and glycyrrhetinic acid, and the vitamins are vitamin A, vitamin B, vitamin B1, and vitamin B1. Examples of the buffering agent E include boric acid, borax, citric acid, and sodium citrate. Further, examples of isotonic agents include potassium chloride, calcium chloride, and sodium chloride, and examples of thickeners include sodium chondroitin sulfate, polyvinyl alcohol, polyvinylpyrrolidone, and hydroxyethyl cellulose.
本発明のフェニレフリン液剤は、安定化剤としてソルビ
ン酸又はその塩をｏ、ｏｏｓ〜０．ＩＷ／Ｖ％含有させ
たことから、アミノ酸もしくはその塩が配合されている
にも拘らず、経日によっても安定であり、また長期間日
光等に曝露されても着色又は変色を生じることがないた
め、プラスチック容器やガラス容器に入れて保存するこ
とができ、しかもその保存ｐＨも通常の点眼剤として好
ましい値である５以上にすることが可能であるため、そ
の使用感にも優れたものである。The phenylephrine solution of the present invention contains sorbic acid or its salt as a stabilizer at o, oos to 0. Because it contains IW/V%, it is stable over time even though it contains amino acids or its salts, and does not become colored or discolored even if exposed to sunlight for a long period of time. Therefore, it can be stored in a plastic or glass container, and its storage pH can be kept at 5 or higher, which is the preferable value for regular eye drops, so it has excellent usability. be.
つぎに、実施例により本発明を更に詳細に説明する。な
お、以下に示す２はいずれもＷ／Ｖ％である。Next, the present invention will be explained in more detail with reference to Examples. In addition, all 2 shown below are W/V%.
実施例１〜１０、比較例１〜６ 表−Ｉに示す配合組成を有する液剤を調製した。Examples 1 to 10, Comparative Examples 1 to 6 A liquid preparation having the formulation shown in Table I was prepared.
つぎに、得られた各液剤を無色のガラスアンプルに入れ
、日光爆射下で２週間、並びに恒温槽中（暗所）に４０
℃及び５０℃で１ケ月保存した後の着色又は変色の程度
を調べた。その結果を表−■に示す。Next, each of the obtained solutions was placed in a colorless glass ampoule and placed under sunlight for 2 weeks and in a constant temperature bath (dark place) for 40 hours.
The degree of coloration or discoloration was examined after storage at 50°C and 50°C for one month. The results are shown in Table-■.
実施１１〜１２
下記に示す配合組成のフェニレフリン液剤１００ＩＩＩ
Ｑを実施例１〜１０と同様な方法で調製し、点眼用容器
に保存した後、前記各実施例と同様な試験に供したとこ
ろ、実施例１〜１０と同様に、着色又は変色がなく使用
感にも優れたものであることが判った・
実施例１１
メチル硫酸ネオスチグミン ０．００２Ｗ／Ｖ％
アスパラギン酸カリウム １．０マレイン酸
クロルフエニラミン ０．０２塩酸フエニレフリン
０．１塩化ベンザルコニウム
０．０１ホウ酸 １
ソルビン酸 ０．０３精製水
適量実施例１２Examples 11-12 Phenylephrine liquid preparation 100III with the formulation shown below
Q was prepared in the same manner as in Examples 1 to 10, stored in an eye drop container, and then subjected to the same tests as in each of the above Examples. As in Examples 1 to 10, no coloring or discoloration was observed. It was found that the product had excellent usability. Example 11 Neostigmine methyl sulfate 0.002W/V%
Potassium aspartate 1.0 Chlorpheniramine maleate 0.02 Phenylephrine hydrochloride
0.1 benzalkonium chloride
0.01 Boric acid 1 Sorbic acid 0.03 Purified water
Appropriate amount Example 12
Claims (1)
の塩を配合した液剤であって、更にソルビン酸又はその
塩を０．００５〜０．１Ｗ／Ｖ％含有させたことを特徴
とする安定化されたフェニレフリン系液剤。(1) A stabilized phenylephrine-based liquid preparation containing a phenylephrine-based compound and an amino acid or its salt, which further contains 0.005 to 0.1 W/V% of sorbic acid or its salt. Liquid agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17717286A JPH0780760B2 (en) | 1986-07-28 | 1986-07-28 | Stabilized phenylephrine liquid agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17717286A JPH0780760B2 (en) | 1986-07-28 | 1986-07-28 | Stabilized phenylephrine liquid agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6333327A true JPS6333327A (en) | 1988-02-13 |
| JPH0780760B2 JPH0780760B2 (en) | 1995-08-30 |
Family
ID=16026442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17717286A Expired - Fee Related JPH0780760B2 (en) | 1986-07-28 | 1986-07-28 | Stabilized phenylephrine liquid agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0780760B2 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59229907A (en) * | 1983-05-13 | 1984-12-24 | Rohm Co Ltd | Detecting circuit |
| JPS6442424A (en) * | 1987-08-08 | 1989-02-14 | Taisho Pharmaceutical Co Ltd | Ophthalmic solution |
| EP0858803A4 (en) * | 1995-08-28 | 2000-02-09 | Showa Pharm Chem Ind | Composition for local anesthesia |
| JP2006312628A (en) * | 2005-04-08 | 2006-11-16 | Rohto Pharmaceut Co Ltd | Aqueous composition containing acitazanolast |
| JP2008532985A (en) * | 2005-03-09 | 2008-08-21 | ラボラトワール・テアッシュウア | Novel ophthalmic composition and method of use thereof |
| JP2010502564A (en) * | 2006-08-28 | 2010-01-28 | 千寿製薬株式会社 | Ophthalmic transdermal preparation |
| AU2007242419B2 (en) * | 2006-04-21 | 2012-08-30 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| US10022339B2 (en) | 2006-04-21 | 2018-07-17 | The Procter & Gamble Company | Compositions and methods useful for treatment of respiratory illness |
| WO2021246172A1 (en) * | 2020-06-05 | 2021-12-09 | ライオン株式会社 | Ophthalmic composition, photostabilization method and method for suppressing discoloration |
-
1986
- 1986-07-28 JP JP17717286A patent/JPH0780760B2/en not_active Expired - Fee Related
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59229907A (en) * | 1983-05-13 | 1984-12-24 | Rohm Co Ltd | Detecting circuit |
| JPS6442424A (en) * | 1987-08-08 | 1989-02-14 | Taisho Pharmaceutical Co Ltd | Ophthalmic solution |
| EP0858803A4 (en) * | 1995-08-28 | 2000-02-09 | Showa Pharm Chem Ind | Composition for local anesthesia |
| JP2008532985A (en) * | 2005-03-09 | 2008-08-21 | ラボラトワール・テアッシュウア | Novel ophthalmic composition and method of use thereof |
| JP2006312628A (en) * | 2005-04-08 | 2006-11-16 | Rohto Pharmaceut Co Ltd | Aqueous composition containing acitazanolast |
| US10098873B2 (en) | 2006-04-21 | 2018-10-16 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| AU2007242419B2 (en) * | 2006-04-21 | 2012-08-30 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| US10022339B2 (en) | 2006-04-21 | 2018-07-17 | The Procter & Gamble Company | Compositions and methods useful for treatment of respiratory illness |
| US10688089B2 (en) | 2006-04-21 | 2020-06-23 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| US10772848B2 (en) | 2006-04-21 | 2020-09-15 | The Procter & Gamble Company | Compositions and methods useful for treatment of respiratory illness |
| US11077074B2 (en) | 2006-04-21 | 2021-08-03 | The Procter & Gamble Company | Compositions and methods useful for treatment of respiratory illness |
| US11083697B2 (en) | 2006-04-21 | 2021-08-10 | The Procter & Gamble Company | Compositions and methods useful for treatment of respiratory illness |
| US11141415B2 (en) | 2006-04-21 | 2021-10-12 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| US11491151B2 (en) | 2006-04-21 | 2022-11-08 | The Procter & Gamble Company | Compositions and kits useful for treatment of respiratory illness |
| JP2010502564A (en) * | 2006-08-28 | 2010-01-28 | 千寿製薬株式会社 | Ophthalmic transdermal preparation |
| WO2021246172A1 (en) * | 2020-06-05 | 2021-12-09 | ライオン株式会社 | Ophthalmic composition, photostabilization method and method for suppressing discoloration |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0780760B2 (en) | 1995-08-30 |
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