JP2005330271A - Liquid agent for eyedrop - Google Patents
Liquid agent for eyedrop Download PDFInfo
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- JP2005330271A JP2005330271A JP2005121857A JP2005121857A JP2005330271A JP 2005330271 A JP2005330271 A JP 2005330271A JP 2005121857 A JP2005121857 A JP 2005121857A JP 2005121857 A JP2005121857 A JP 2005121857A JP 2005330271 A JP2005330271 A JP 2005330271A
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- ophthalmic solution
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- 239000003889 eye drop Substances 0.000 title abstract description 21
- 239000003795 chemical substances by application Substances 0.000 title abstract description 5
- 239000007788 liquid Substances 0.000 title abstract description 5
- 239000004094 surface-active agent Substances 0.000 claims abstract description 13
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical class O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002997 ophthalmic solution Substances 0.000 claims description 20
- 229940054534 ophthalmic solution Drugs 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 13
- 239000003755 preservative agent Substances 0.000 claims description 13
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 11
- 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 claims description 9
- 229940046978 chlorpheniramine maleate Drugs 0.000 claims description 9
- 229940107200 chondroitin sulfates Drugs 0.000 claims description 9
- -1 polyethylene Polymers 0.000 claims description 9
- 230000002335 preservative effect Effects 0.000 claims description 8
- 239000004698 Polyethylene Substances 0.000 claims description 6
- 229920000573 polyethylene Polymers 0.000 claims description 6
- 229940074774 glycyrrhizinate Drugs 0.000 claims description 5
- 229940009662 edetate Drugs 0.000 claims description 4
- 229940012356 eye drops Drugs 0.000 abstract description 12
- 230000002378 acidificating effect Effects 0.000 abstract description 6
- 238000002156 mixing Methods 0.000 abstract description 6
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical class FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000243 solution Substances 0.000 abstract description 3
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 239000008213 purified water Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910021538 borax Inorganic materials 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000004328 sodium tetraborate Substances 0.000 description 6
- 235000010339 sodium tetraborate Nutrition 0.000 description 6
- 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 5
- 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 4
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 4
- 231100000040 eye damage Toxicity 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 3
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229960002684 aminocaproic acid Drugs 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 229940006423 chondroitin sulfate sodium Drugs 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 229940045613 taurine 1000 mg Drugs 0.000 description 3
- 229940021790 tetrahydrozoline hydrochloride Drugs 0.000 description 3
- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000002738 chelating agent 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
- 238000011109 contamination Methods 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 229940048820 edetates Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Abstract
Description
本発明は点眼用液剤に関し、さらに詳しくは防腐剤、界面活性剤を配合しなくても安定に保存できる点眼用液剤に関する。 The present invention relates to an ophthalmic solution, and more particularly to an ophthalmic solution that can be stored stably without blending a preservative and a surfactant.
点眼剤は、眼に直接投与する形態の薬剤であるため、その安全性や使用感は非常に重要である。 Since eye drops are drugs that are administered directly to the eye, their safety and feeling of use are very important.
点眼剤は無菌製剤であり、従来から２次汚染防止のために防腐剤を使用して防腐性を確保してきた。しかし、点眼剤に配合される防腐剤や界面活性剤がソフトコンタクトレンズに吸着しやすいことから、ソフトコンタクトレンズ使用者に対する点眼剤の使用は大幅に制限されたものであった。さらに、点眼剤に防腐剤の配合を嫌う使用者もいることから、防腐剤無配合の点眼剤が望まれる傾向にある。 An eye drop is a sterile preparation and has been used to ensure antiseptic properties by using antiseptics to prevent secondary contamination. However, since preservatives and surfactants blended in eye drops are easily adsorbed to soft contact lenses, the use of eye drops for soft contact lens users has been greatly limited. Furthermore, since some users dislike the addition of preservatives to eye drops, eye drops without preservatives tend to be desired.
そのような問題点を解決するため、最近は一回使い切りのユニットドーズ型点眼剤が市販されている。これは防腐剤を必要とせず、また使い切りのため開封後の雑菌やカビの繁殖の問題がないという利点がある。さらに携帯性に優れるという利便性も有している。 In order to solve such problems, unit dose type eye drops that have been used once have been recently marketed. This has the advantage that no preservative is required and there is no problem of propagation of germs and mold after opening because it is used up. Furthermore, it has the convenience of excellent portability.
それらのユニットドーズ型点眼剤は、防腐剤を配合しなくても品質保持が可能なことから眼障害を発生しにくい効果が期待できる反面、有効成分、溶解補助剤などが容器に吸着してしまうことから、配合できる成分は限られたものだけであった。特にマレイン酸クロルフェニラミンなどの塩基性薬物は容器に吸着しやすいためユニットドーズ型容器には配合が困難であった。 These unit dose type eye drops can maintain the quality without blending preservatives, so that they can be expected to prevent eye damage, but the active ingredients, solubilizing agents, etc. are adsorbed to the container. Therefore, only a limited number of components can be blended. In particular, since basic drugs such as chlorpheniramine maleate are easily adsorbed to the container, it is difficult to mix them in the unit dose type container.
従来、コンドロイチン硫酸塩類、グリチルリチン酸塩類、第４級アンモニウム性陽イオンおよび非イオン界面活性剤を同時に配合し、白濁を解消した技術が開示されている（特許文献１）。 Conventionally, a technique has been disclosed in which chondroitin sulfates, glycyrrhizinates, a quaternary ammonium cation and a nonionic surfactant are blended simultaneously to eliminate white turbidity (Patent Document 1).
本発明者らは有効成分を配合したユニットドーズ型点眼剤の検討過程で、配合成分に角膜保護作用のあるコンドロイチン硫酸塩類、抗炎症作用のあるグリチルリチン酸塩類を同時配合した製剤の製造を試みた。しかしながら、そこに塩基性薬物を配合すると、そのときの液性が中性〜アルカリ性の領域であると塩基性薬物がポリエチレン製の容器に吸着してしまうことがわかった。一方、液性を酸性領域にすると、コンドロイチン硫酸塩類およびグリチルリチン酸塩類由来の沈殿が析出してしまうことがわかった。 In the course of studying unit dose type eye drops containing an active ingredient, the present inventors tried to produce a preparation containing a combination of chondroitin sulfate having a cornea-protecting action and glycyrrhizinate having an anti-inflammatory action. . However, it has been found that when a basic drug is added thereto, the basic drug is adsorbed to a polyethylene container when the liquidity at that time is in a neutral to alkaline region. On the other hand, it was found that precipitation from chondroitin sulfates and glycyrrhizinates was deposited when the liquidity was in the acidic region.
ここで、液剤において沈殿物が析出する場合には、界面活性剤を配合して沈殿物を溶解する方法が一般的である。しかしながら、酸性領域でコンドロイチン硫酸塩類およびグリチルリチン酸塩類を同時配合した系に界面活性剤を配合すると、経時的に着色してしまい商品性の低下を招くことがわかった。さらに、そこに塩基性薬物を配合した場合、界面活性剤はそれらの成分の容器への吸着も促進することがわかった。 Here, when a precipitate is deposited in the liquid agent, a method of dissolving the precipitate by adding a surfactant is generally used. However, it has been found that when a surfactant is blended in a system in which chondroitin sulfates and glycyrrhizinate are blended simultaneously in the acidic region, the coloration occurs over time, leading to a reduction in merchantability. Furthermore, it has been found that when a basic drug is added thereto, the surfactant also promotes the adsorption of these components to the container.
本発明は、酸性領域でコンドロイチン硫酸塩類およびグリチルリチン酸塩類を同時配合した系で安定な点眼剤を提供することを目的とする。 An object of the present invention is to provide an eye drop that is stable in a system in which chondroitin sulfates and glycyrrhizinates are simultaneously blended in an acidic region.
本発明者らは課題を解決するために検討した結果、界面活性剤、防腐剤を実質的に配合しない酸性領域の点眼用液剤に、コンドロイチン硫酸塩類およびグリチルリチン酸塩類を配合したなかに、さらにエデト酸塩類を配合すると、沈殿が析出せず、経時的な着色も抑制でき、塩基性薬物などの有効成分の容器への吸着も促進しない安定な点眼剤が得られることを見出し本発明を完成した。 As a result of investigations to solve the problems, the present inventors have found that even when chondroitin sulfates and glycyrrhizinates are added to an eye drop solution in an acidic region that does not substantially contain a surfactant or preservative, The present invention was completed by finding that when an acid salt is added, a stable eye drop can be obtained in which precipitation does not occur, coloring over time can be suppressed, and adsorption of an active ingredient such as a basic drug to a container is not promoted. .
すなわち本発明は、
１．コンドロイチン硫酸塩類、グリチルリチン酸塩類およびエデト酸塩類を配合し、界面活性剤および防腐剤を実質的に配合せず、ｐＨが５〜６．５である点眼用液剤。
２．ポリエチレン製の容器に封入したことを特徴とする１に記載の点眼用液剤。
３．ユニットドーズ型容器に封入したことを特徴とする１に記載の点眼用液剤。
４．さらに塩基性薬物を配合したことを特徴とする１〜３に記載の点眼用液剤。
５．塩基性薬物がマレイン酸クロルフェニラミンである４記載の点眼用液剤。
である。
That is, the present invention
1. An ophthalmic solution containing chondroitin sulfates, glycyrrhizinates and edetates, substantially free of surfactants and preservatives, and having a pH of 5 to 6.5.
2. 2. The ophthalmic solution according to 1, which is sealed in a polyethylene container.
3. 2. The ophthalmic solution according to 1, which is enclosed in a unit dose type container.
4). The ophthalmic solution according to 1 to 3, further comprising a basic drug.
5). 5. The ophthalmic solution according to 4, wherein the basic drug is chlorpheniramine maleate.
It is.
本発明において、好ましいコンドロイチン硫酸塩類として、コンドロイチン硫酸ナトリウムをあげることができる。 In the present invention, preferred chondroitin sulfates include sodium chondroitin sulfate.
本発明において、コンドロイチン硫酸塩類の配合量は製剤全体の0.005〜1(w/v)%である。 In the present invention, the amount of chondroitin sulfate is 0.005 to 1 (w / v)% of the whole preparation.
本発明でグリチルリチン酸塩類とは、薬効成分として点眼剤に配合できる成分を用いることができ、好ましいものとしてグリチルリチン酸ジカリウムをあげることができる。 In the present invention, as the glycyrrhizinate, a component that can be blended in eye drops as a medicinal component can be used, and preferable examples include dipotassium glycyrrhizinate.
グリチルリチン酸塩類の配合量は製剤全体の0.005〜0.5(w/v)%である。 The amount of glycyrrhizinate is 0.005 to 0.5 (w / v)% of the whole preparation.
本発明においてエデト酸塩類とはキレート剤、酸化防止剤などとして一般的に使われるエチレンジアミン四酢酸二ナトリウム（エデト酸二ナトリウム）、エチレンジアミン四酢酸カルシウム二ナトリウムなどを使用することができるが、好ましいものとしてエチレンジアミン四酢酸二ナトリウムをあげることができる。 In the present invention, edetate may be disodium ethylenediaminetetraacetate (disodium edetate) or disodium ethylenediaminetetraacetate, which is generally used as a chelating agent or an antioxidant, but is preferable. Examples thereof include disodium ethylenediaminetetraacetate.
本発明においてエデト酸塩類の配合量は、0.001〜0.15(w/v)%が好ましい。0.001(w/v)%未満であると、沈殿防止の効果が不十分であるからである。 In the present invention, the amount of edetate is preferably 0.001 to 0.15 (w / v)%. This is because if it is less than 0.001 (w / v)%, the effect of preventing precipitation is insufficient.
本発明では界面活性剤および防腐剤を実質的に配合しないことを特徴とする。それらの成分は、ソフトコンタクトレンズに吸着し、眼障害に発展するおそれがあるからである。したがって、本発明の点眼剤はソフトコンタクトレンズ使用者に特に好適に用いることができるが、その他の使用者に対しても、より眼障害の危険性が少ない点眼剤として使用することができる。 In the present invention, a surfactant and a preservative are not substantially blended. This is because these components may be adsorbed on the soft contact lens and develop eye damage. Therefore, the eye drop of the present invention can be particularly suitably used for soft contact lens users, but can also be used as an eye drop with less risk of eye damage for other users.
本発明においては、界面活性剤または防腐剤を実質的に配合しないが、配合する原料に界面活性剤または防腐剤が含まれることにより、製剤中に極めて微量が混在してしまうような場合など、眼障害の危険性が極めて少ないものは実質的に配合しないものに包含される。 In the present invention, a surfactant or a preservative is not substantially blended, but when a surfactant or a preservative is included in the blended raw material, a very small amount is mixed in the preparation, etc. Those that have a very low risk of eye damage are included in those that are not substantially blended.
本発明では液剤のｐＨは５〜６．５の範囲である必要がある。６．５を超えると配合成分が容器に吸着してしまい、５未満であると点眼時に刺激が生じる可能性があるからである。 In the present invention, the pH of the solution needs to be in the range of 5 to 6.5. This is because if it exceeds 6.5, the blended components are adsorbed in the container, and if it is less than 5, irritation may occur during instillation.
本発明の点眼用液剤は成分が吸着しやすいポリエチレン製の容器を用いるときに特に有効である。また、防腐剤を配合しないことから、液剤の品質保持のためユニットドーズ型の容器が特に好ましい。 The ophthalmic solution of the present invention is particularly effective when a polyethylene container that easily adsorbs components is used. Moreover, since a preservative is not blended, a unit dose type container is particularly preferable for maintaining the quality of the liquid agent.
本発明はさらに塩基性薬物などの成分を配合しても、それらの成分が容器に吸着しないという特徴も併せ持っている。ここで、本発明で好ましい効果が得られる塩基性薬物としてマレイン酸クロルフェニラミンをあげることができる。 The present invention also has a feature that even if components such as a basic drug are blended, these components do not adsorb to the container. Here, chlorpheniramine maleate can be mentioned as a basic drug that can provide a favorable effect in the present invention.
本発明の点眼用液剤は本発明の効果を損なわない範囲で、通常点眼剤に配合される成分を配合して、通常の方法で製造することができる。 The ophthalmic solution of the present invention can be produced by a usual method by blending components that are usually blended into eye drops within a range that does not impair the effects of the present invention.
本発明により、酸性領域でコンドロイチン硫酸塩類およびグリチルリチン酸塩類を同時配合しても安定な点眼剤を提供することが可能になった。 According to the present invention, it has become possible to provide a stable eye drop even when chondroitin sulfates and glycyrrhizinates are blended simultaneously in an acidic region.
以下、本発明を実施例および試験例によりさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to examples and test examples.
コンドロイチン硫酸ナトリウム 100mg
グリチルリチン酸ジカリウム 250mg
マレイン酸クロルフェニラミン 30mg
塩酸テトラヒドロゾリン 50mg
ε-アミノカプロン酸 1000mg
タウリン 1000mg
エデト酸二ナトリウム 3mg
ホウ酸 500mg
ホウ砂 適量
塩化ナトリウム 88.4mg
精製水 適量
精製水に各成分を溶解し、ホウ砂でｐＨ６．０に調整して、精製水で全量を１００ｍＬにした。得られた点眼液をポリエチレン製ユニットドーズ容器に０．５ｍL無菌充填した。この点眼液の浸透圧は２８２ｍＯｓｍであった。
Chondroitin sulfate sodium 100mg
Dipotassium glycyrrhizinate 250mg
Chlorpheniramine maleate 30mg
Tetrahydrozoline hydrochloride 50mg
ε-Aminocaproic acid 1000mg
Taurine 1000mg
Edetate disodium 3mg
Boric acid 500mg
Borax appropriate amount Sodium chloride 88.4mg
Purified water appropriate amount Each component was dissolved in purified water, adjusted to pH 6.0 with borax, and made up to 100 mL with purified water. The obtained ophthalmic solution was aseptically filled with 0.5 mL into a polyethylene unit dose container. The osmotic pressure of this ophthalmic solution was 282 mOsm.
比較例１
コンドロイチン硫酸ナトリウム 100mg
グリチルリチン酸ジカリウム 250mg
マレイン酸クロルフェニラミン 30mg
塩酸テトラヒドロゾリン 50mg
ε-アミノカプロン酸 1000mg
タウリン 1000mg
ホウ酸 500mg
ホウ砂 適量
塩化ナトリウム 88.4mg
精製水 適量
精製水に各成分を溶解し、ホウ砂でｐＨ６．０に調整して精製水で全量を１００ｍＬにした。点眼液をポリエチレン製ユニットドーズ容器に０．５ｍL無菌充填した。この点眼液の浸透圧は２８３ｍＯｓｍであった。
Comparative Example 1
Chondroitin sulfate sodium 100mg
Dipotassium glycyrrhizinate 250mg
Chlorpheniramine maleate 30mg
Tetrahydrozoline hydrochloride 50mg
ε-Aminocaproic acid 1000mg
Taurine 1000mg
Boric acid 500mg
Borax appropriate amount Sodium chloride 88.4mg
Purified water appropriate amount Each component was dissolved in purified water, adjusted to pH 6.0 with borax and made up to 100 mL with purified water. The ophthalmic solution was aseptically filled in a polyethylene unit dose container in an amount of 0.5 mL. The osmotic pressure of this ophthalmic solution was 283 mOsm.
比較例２
コンドロイチン硫酸ナトリウム 100mg
グリチルリチン酸ジカリウム 250mg
マレイン酸クロルフェニラミン 30mg
塩酸テトラヒドロゾリン 50mg
ε-アミノカプロン酸 1000mg
タウリン 1000mg
ポリソルベート８０ 100mg
（商品名：ニッコールＴＯ−１０Ｍ）
ホウ酸 500mg
ホウ砂 適量
塩化ナトリウム 88.4mg
精製水 適量
精製水に各成分を溶解し、ホウ砂でｐＨ６．０に調整して全量を１００ｍＬにした。点眼液をポリエチレン製ユニットドーズ容器に０．５ｍL無菌充填した。この点眼液の浸透圧は２８２ｍＯｓｍであった。
Comparative Example 2
Chondroitin sulfate sodium 100mg
Dipotassium glycyrrhizinate 250mg
Chlorpheniramine maleate 30mg
Tetrahydrozoline hydrochloride 50mg
ε-Aminocaproic acid 1000mg
Taurine 1000mg
Polysorbate 80 100mg
(Product name: Nikkor TO-10M)
Boric acid 500mg
Borax appropriate amount Sodium chloride 88.4mg
Purified water appropriate amount Each component was dissolved in purified water and adjusted to pH 6.0 with borax to make a total volume of 100 mL. The ophthalmic solution was aseptically filled in 0.5 mL polyethylene unit dose containers. The osmotic pressure of this ophthalmic solution was 282 mOsm.
試験例１
実施例１および比較例１、２の製剤を５０℃で２ヶ月間保存後、目視により沈殿生成の有無を確認した。また、４００ｎｍでの吸光度測定による着色の評価、ポリエチレンに吸着しやすい塩基性薬物であるマレイン酸クロルフェニラミンの残存率をＨＰＬＣ法により測定した。その結果を表1に示した。
Test example 1
After the preparations of Example 1 and Comparative Examples 1 and 2 were stored at 50 ° C. for 2 months, the presence or absence of precipitation was visually confirmed. Further, coloring was evaluated by measuring absorbance at 400 nm, and the residual ratio of chlorpheniramine maleate, which is a basic drug that is easily adsorbed to polyethylene, was measured by HPLC. The results are shown in Table 1.
表から明らかなように、エデト酸塩類を配合すると、着色の原因となる界面活性剤であるポリソルベート８０を用いなくても沈殿は生成しないことがわかった。さらに、ポリエチレンに吸着しやすいマレイン酸クロルフェニラミンは、ポリソルベート８０の添加により吸着が促進されるが、本発明組成物はこの吸着に影響しないこともわかった。 As is apparent from the table, it was found that when edetate was added, no precipitate was formed without using polysorbate 80, which is a surfactant causing coloration. Furthermore, although chlorpheniramine maleate, which is easily adsorbed on polyethylene, is promoted by addition of polysorbate 80, it was also found that the composition of the present invention does not affect this adsorption.
本発明により優れた薬効と高い安定性を併せ持った液剤を提供することが可能になったので、点眼剤に使用可能である。 Since it became possible to provide the liquid agent which had the outstanding medicinal effect and high stability by this invention, it can be used for an eye drop.
Claims (5)
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011246449A (en) * | 2010-04-26 | 2011-12-08 | Lion Corp | Ophthalmic composition for soft contact lens |
| JP2012106999A (en) * | 2010-10-29 | 2012-06-07 | Lion Corp | Ophthalmic composition for soft contact lens |
| US10071113B2 (en) | 2012-03-26 | 2018-09-11 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solution comprising diquafosol |
| WO2023182480A1 (en) * | 2022-03-25 | 2023-09-28 | 株式会社坪田ラボ | Aqueous composition |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002003364A (en) * | 2000-06-23 | 2002-01-09 | Lion Corp | Eye drop, ophthalmic composition and method for adsorption control |
| JP2003183157A (en) * | 2001-12-19 | 2003-07-03 | Lion Corp | Ophthalmologic composition |
| JP2004149526A (en) * | 2002-10-11 | 2004-05-27 | Rohto Pharmaceut Co Ltd | Aqueous liquid composition |
| JP2004352666A (en) * | 2003-05-29 | 2004-12-16 | Zeria Pharmaceut Co Ltd | Stable eye lotion |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002003364A (en) * | 2000-06-23 | 2002-01-09 | Lion Corp | Eye drop, ophthalmic composition and method for adsorption control |
| JP2003183157A (en) * | 2001-12-19 | 2003-07-03 | Lion Corp | Ophthalmologic composition |
| JP2004149526A (en) * | 2002-10-11 | 2004-05-27 | Rohto Pharmaceut Co Ltd | Aqueous liquid composition |
| JP2004352666A (en) * | 2003-05-29 | 2004-12-16 | Zeria Pharmaceut Co Ltd | Stable eye lotion |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011246449A (en) * | 2010-04-26 | 2011-12-08 | Lion Corp | Ophthalmic composition for soft contact lens |
| JP2012106999A (en) * | 2010-10-29 | 2012-06-07 | Lion Corp | Ophthalmic composition for soft contact lens |
| US10071113B2 (en) | 2012-03-26 | 2018-09-11 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solution comprising diquafosol |
| US10632139B2 (en) | 2012-03-26 | 2020-04-28 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solution comprising diquafosol |
| US11166974B2 (en) | 2012-03-26 | 2021-11-09 | Santen Pharmaceutical Co., Ltd. | Ophthalmic solution comprising Diquafosol |
| WO2023182480A1 (en) * | 2022-03-25 | 2023-09-28 | 株式会社坪田ラボ | Aqueous composition |
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