JP2563336B2 - Eye drops for promoting corneal penetration - Google Patents
Eye drops for promoting corneal penetrationInfo
- Publication number
- JP2563336B2 JP2563336B2 JP62137921A JP13792187A JP2563336B2 JP 2563336 B2 JP2563336 B2 JP 2563336B2 JP 62137921 A JP62137921 A JP 62137921A JP 13792187 A JP13792187 A JP 13792187A JP 2563336 B2 JP2563336 B2 JP 2563336B2
- Authority
- JP
- Japan
- Prior art keywords
- bunazosin
- eye drops
- acid
- permeability
- prazosin
- 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.)
- Expired - Lifetime
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Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は角膜透過促進点眼剤に関し、詳しくは角膜透
過性の良好なブナゾシン又はプラゾシン含有点眼剤に関
する。TECHNICAL FIELD The present invention relates to eye drops for promoting corneal permeation, and more particularly to eye drops containing bunazosin or prazosin having good corneal permeability.
ブナゾシン又はプラゾシンは抗圧剤として知られてお
り、現在経口投与により用いられている。Bunazosin or prazosin is known as an anti-pressure agent, and is currently used by oral administration.
これらの薬物は微量で著名な薬理効果を示すため、非
経口的な投与法も有効な治療手段となる可能性がある。
例えば眼科領域において、ブナゾシンのα1−ブロッカ
ーを点眼投与した場合、有意な眼内圧低下作用が認めら
れたことから、緑内障の治療薬としての開発の可能性が
考えられる。Since these drugs show prominent pharmacological effects even in trace amounts, parenteral administration may be an effective therapeutic means.
For example, in the field of ophthalmology, when an α 1 -blocker of bunazosin was administered by instillation, a significant effect of lowering the intraocular pressure was observed, so it is considered possible to develop it as a therapeutic agent for glaucoma.
このような利用を考えた場合、局所的な作用（例えば
眼内圧低下）と全身的な作用（降圧作用）が分離される
ことが望ましい。このためには局所での生体膜透過性の
優れていることが必要となる。In consideration of such use, it is desirable to separate the local action (for example, reduction of intraocular pressure) and the systemic action (hypotensive action). For this purpose, it is necessary to have excellent local biomembrane permeability.
角膜透過性とオクタノール／水の分配率とに相関関係
があり、オクタノールへの溶解性が大きいものほど角膜
透過性が大きいことが報告されている〔Journal of Pha
rmaceutical Sciences,67（６）,786（1978）〕。ブナ
ゾシンはpKaが7.6で高いpH域ではオクタノール／水の分
配率が約２となり、角膜透過性の良いことが予想される
が、通常点眼剤として用いられるpH8以下の領域ではこ
の分配率が高くなく、ブナゾシンを点眼剤として用いる
場合には改善の余地がある。It has been reported that there is a correlation between the corneal permeability and the partition ratio of octanol / water, and that the greater the solubility in octanol, the greater the corneal permeability [Journal of Pha
rmaceutical Sciences, 67 (6), 786 (1978)]. Although bunazosin has a pKa of 7.6 and a partition ratio of octanol / water of about 2 in the high pH range, it is expected to have good corneal permeability, but this partition ratio is not high in the pH range of 8 or lower, which is usually used as eye drops. However, there is room for improvement when using bunazosin as an eye drop.
本発明者らは上記の問題点を解決すべく鋭意研究の結
果、生体が許容し得るアニオン（ペアードイオン）を用
いてブナゾシン又はプラゾシンとの安定なコンプレック
ス又は塩を形成させ、オクタノール／水の分配率を約２
程度に調整することにより、生体膜の透過性を改善し、
ブナゾシン又はプラゾシンを含有する有効な点眼剤が得
られることを見出し本発明に到った。As a result of intensive studies to solve the above-mentioned problems, the present inventors have formed a stable complex or salt with bunazosin or prazosin using an anion (paired ion) that a living body can accept, and octanol / water. Distribution rate about 2
By adjusting the degree, improve the permeability of the biological membrane,
It was found that an effective eye drop containing bunazosin or prazosin can be obtained, and the present invention has been completed.
即ち、本発明は、ブナゾシンに、炭素数６〜10の直鎖
脂肪酸、炭素数６〜10のアルキルスルホン酸、リン酸又
はクエン酸、或いはこれらの塩を配合してなるか、もし
くはプラゾシンに、炭素数６〜10の直鎖脂肪酸又は炭素
数６〜10のアルキルスルホン酸、或いはこれらの塩を配
合してなる角膜透過促進点眼剤を提供するものである。That is, the present invention is obtained by blending bunazosin with a linear fatty acid having 6 to 10 carbon atoms, an alkylsulfonic acid having 6 to 10 carbon atoms, phosphoric acid or citric acid, or a salt thereof, or prazosin. A corneal permeation-promoting eye drop comprising a straight chain fatty acid having 6 to 10 carbon atoms, an alkylsulfonic acid having 6 to 10 carbon atoms, or a salt thereof.
本発明に用いられる炭素数６〜10の直鎖脂肪酸として
は、カプロン酸、カプリル酸、カプリン酸等が挙げられ
る。また炭素数６〜10のアルキルスルホン酸としてはヘ
キシルスルホン酸、オクチルスルホン酸、デシルスルホ
ン酸等が挙げられる。Examples of the linear fatty acid having 6 to 10 carbon atoms used in the present invention include caproic acid, caprylic acid, capric acid and the like. Examples of the alkyl sulfonic acid having 6 to 10 carbon atoms include hexyl sulfonic acid, octyl sulfonic acid and decyl sulfonic acid.
本発明の点眼剤中のブナゾシン又はプラゾシンの配合
量は0.001〜0.5重量％が好ましい。またブナゾシン又は
プラゾシンと酸類との配合割合は、モル比で1:1が好ま
しい。The compounding amount of bunazosin or prazosin in the eye drop of the present invention is preferably 0.001 to 0.5% by weight. Further, the blending ratio of bunazosin or prazosin and the acids is preferably 1: 1 in molar ratio.
本発明の点眼剤には、上記必須成分の他の公知の点眼
剤に用いられる界面活性剤、安定剤、保存剤、防腐剤等
を適宜配合することができる。The eye drop of the present invention can be appropriately blended with a surfactant, a stabilizer, a preservative, a preservative and the like which are used in other known eye drops of the above essential components.
以下に、本発明の効果を一層明らかにするめに実験例
及び実施例を示すが、本発明はこれらの実施例に限定さ
れるものではない。Experimental examples and examples will be shown below in order to further clarify the effects of the present invention, but the present invention is not limited to these examples.
実験例１ ブナゾシン2.4mM（0.1％）水溶液に、表１に示す各種
の酸を、ブナゾシン：酸類のモル比が1:1となるように
配合し、そのオクタノール／水の分配率を測定した。但
し、NaOH又はHClで全てpH7.5に調節した。Experimental Example 1 Various acids shown in Table 1 were added to a bunazosin 2.4 mM (0.1%) aqueous solution so that the molar ratio of bunazosin: acids was 1: 1, and the octanol / water partition ratio was measured. However, pH was adjusted to 7.5 with NaOH or HCl.
結果を表１に示す。 Table 1 shows the results.
第１表から明からな如く、本発明試料はオクタノール
／水の分配率が大きく、従って角膜透過性が大きいこと
がわかる〔Journal of Pharmaceutical Sciences,67
（６）,786（1978）参照〕。 As is clear from Table 1, the sample of the present invention is octanol.
/ Large water distribution and therefore large corneal permeability
Is understood [Journal of Pharmaceutical Sciences,67
(6), 786 (1978)].
実験例２ 直鎖脂肪酸の炭素数の角膜透過に及ぼす影響を調べる
ために下記に示す方法によりin Vitro角膜透過実験を行
った。Experimental Example 2 An in vitro corneal permeation experiment was carried out by the method described below in order to investigate the influence of the carbon number of a straight-chain fatty acid on the corneal permeation.
〈実験液の調製〉 ブナゾシン2.4mM（0.1％）水溶液に、各種直鎖脂肪酸
（Ｒ−COOHのＲをC3〜C9まで変えたもの）を、ブナゾシ
ン：直鎖脂肪酸のモル比が1:1となるように配合し、更
にNaOH又はHClによりpHを6.5及び7.5に調整して実験液
を作成した。A bunazosin 2.4 mM (0.1%) aqueous solution <Preparation of experimental solution>, various straight-chain fatty acids (obtained by changing the R of R-COOH to C 3 -C 9), bunazosin molar ratio of linear fatty acid is 1: The test solution was prepared by blending so as to be 1 and further adjusting the pH to 6.5 and 7.5 with NaOH or HCl.
〈in Vitro角膜透過実験〉 第１図に示すようなセル１に家兎からの摘出角膜２を
固定し、片側に人工房水３、もう一方に実験液４を入
れ、各実験液の角膜透過係数を求めた。<In Vitro Corneal Permeation Experiment> The cornea 2 extracted from the rabbit was fixed to the cell 1 as shown in FIG. The coefficient was calculated.
結果を第２図に示す。 Results are shown in FIG.
第２図から明らかなように、ＲがC5〜C9即ち炭素数６
〜10の直鎖脂肪酸が良好な透過性を示し、又、pH7.5の
方が透過性が優れていることがわかる。As is clear from FIG. 2, R is C 5 to C 9, that is, carbon number 6
It can be seen that straight chain fatty acids of up to 10 show good permeability, and that pH 7.5 has better permeability.
実験例３ 酸類自身が角膜を傷付けていないことを証明するため
に、以下に示す３種類の方法により、実験例２と同様な
in Vitro角膜透過実験を行った。Experimental Example 3 In order to prove that the acids themselves did not damage the cornea, the same as in Experimental Example 2 was performed by the following three types of methods.
An in vitro corneal permeation experiment was performed.
結果を第３図に示す。 Results are shown in FIG.
方法−１ ブナゾシン2.4mM（0.1％）水溶液にカプリル酸ナトリ
ウムを、ブナゾシン：カプリル酸ナトリウムのモル比が
1:1となるように配合した溶液を実験液とした。Method-1 Sodium caprylate was added to a 2.4 mM (0.1%) bunazosin aqueous solution at a bunazosin: sodium caprylate molar ratio.
A solution prepared to be 1: 1 was used as an experimental solution.
方法−２ 方法−１の溶液からカプリル酸ナトリウムを除いたブ
ナゾシンのみの水溶液を実験液とした。Method-2 An aqueous solution of only bunazosin obtained by removing sodium caprylate from the solution of Method-1 was used as an experimental solution.
方法−３ まずカプリル酸ナトリウム水溶液で角膜の上皮側を30
分間インキュベートした後、生理食塩水でよく洗浄し、
その後、方法−２と同様のブナゾシン水溶液を加えた。Method-3 First, the epithelial side of the cornea is treated with an aqueous sodium caprylate solution.
After incubating for a minute, wash well with physiological saline,
Then, the same bunazosin aqueous solution as in Method-2 was added.
第３図の結果から明らかなように、方法−１の透過性
が良好で、方法−２と３は透過性がほとんど変わらない
ことから、角膜に酸が作用するのではなく、ブナゾシン
と酸とがコンプレックスを作ったために透過性が上がっ
たことがわかる。As is clear from the results of FIG. 3, the permeability of Method-1 is good, and the permeability of Methods-2 and 3 is almost the same. Therefore, acid does not act on the cornea, but bunazosin and acid It can be seen that the transparency increased because the complex was made.
実験例４ ブナゾシンとカプリル酸ナトリウムとのモル比を種々
変えて、実験例２と同様にin Vitro角膜透過実験を行っ
た。Experimental Example 4 An in vitro corneal permeation experiment was carried out in the same manner as in Experimental Example 2 with various molar ratios of bunazosin and sodium caprylate being changed.
結果を第４図に示す。 Results are shown in FIG.
第４図から明らかなようにブナゾシンとカプリル酸ナ
トリウムとはモル比1:1の添加が最も好ましいことがわ
かる。As is clear from FIG. 4, it is most preferable to add bunazosin and sodium caprylate at a molar ratio of 1: 1.
実験例５ ブナゾシンの代わりにプラゾシンを用い、プラゾシン
2.4mM（0.1％）水溶液にカプリル酸ナトリウムを、プラ
ゾシン：カプリル酸ナトリウムのモル比が1:1となるよ
うに配合した溶液、及びカプリル酸ナトリウム無添加の
溶液を実験液として、実験例２と同様にin Vitro角膜透
過実験を行った。Experimental Example 5 Prazosin was used instead of bunazosin.
A solution prepared by adding sodium caprylate to a 2.4 mM (0.1%) aqueous solution so that the molar ratio of prazosin: sodium caprylate was 1: 1 and a solution without addition of sodium caprylate were used as experimental solutions. Similarly, an in vitro corneal permeation experiment was performed.
結果を表２に示す。 The results are shown in Table 2.
実験例６（in vivo） 塩酸ブナゾシン 0.5g CH3(CH2)6COONa 0.2 グリセリン 2.3 NaOH 適量 滅菌精製水 全100ml 上記組成の点眼液（pH7.5）20mlを白色家兎の右眼に
点眼後、経時的に房水をサンプリングし、ブナゾシン濃
度を測定した。又、コントロールとして上記点眼液から
CH3(CH2)6COONaを除いたものについても同様に実験し
た。 Experimental Example 6 (in vivo) Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 6 COONa 0.2 Glycerin 2.3 NaOH Suitable amount Sterilized purified water Total 100 ml 20 ml of ophthalmic solution (pH 7.5) of the above composition was applied to the right eye of a white rabbit. The aqueous humor was sampled over time and the bunazosin concentration was measured. Also, from the above eye drops as a control
The same experiment was carried out with the exception of CH 3 (CH 2 ) 6 COONa.
結果を第５図に示す。 Results are shown in FIG.
第５図から明らかな如く、20分〜30分で本発明の点眼
液はコントロールに対して有意差があった。As is clear from FIG. 5, the eye drop of the present invention was significantly different from the control in 20 to 30 minutes.
実験例７（in vivo） 塩酸ブナゾシン 0.5g CH3(CH2)6COONa 0.2 グリセリン 2.3 NaOH 適量 滅菌精製水 全100ml 上記組成の点眼液（pH7.5）20mlを白色家兎の右眼に
点眼後、経時的に血漿中のブナゾシン濃度を測定した。
又、コントロールとして上記点眼液からCH3(CH2)6COONa
を除いたものについても同様に実験した。Experimental Example 7 (in vivo) Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 6 COONa 0.2 Glycerin 2.3 NaOH Suitable amount Sterilized purified water 100 ml Total 20 ml of eye drops (pH 7.5) of the above composition was applied to the right eye of a white rabbit. The concentration of bunazosin in plasma was measured over time.
As a control, CH 3 (CH 2 ) 6 COONa
The same experiment was carried out for those except.
結果を第６図に示す。 The results are shown in FIG.
第６図から明らかな如く、本発明の点眼液は房水内
（標的部位）のみ薬物濃度を上げて、血漿中は下げる傾
向にあり、体内分散がなくて、副作用の心配がないこと
がわかる。As is clear from FIG. 6, the ophthalmic solution of the present invention tends to increase the drug concentration only in the aqueous humor (target site) and decrease it in the plasma, and there is no dispersion in the body and no fear of side effects. .
実施例１ 塩酸ブナゾシン 0.5g CH3(CH2)6COONa 0.2 グリセリン 2.3 NaOH 適量→pH7.5 滅菌精製水 全100ml 上記組成の点眼剤を調製した。Example 1 Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 6 COONa 0.2 Glycerin 2.3 NaOH proper amount → pH 7.5 sterilized purified water 100 ml All eye drops having the above composition were prepared.
この点眼剤はCH3(CH2)6COONaを含まないものに比べ
て、in Vitroでの透過性、点眼後の房水内濃度のいずれ
も有意に高かった。This eye drop had significantly higher permeability in vitro and higher concentration in the aqueous humor after instillation than that without CH 3 (CH 2 ) 6 COONa.
実施例２ 塩酸ブナゾシン 0.5g CH3(CH2)8COONa 0.24 グリセリン 2.3 NaOH 適量→pH7.5 滅菌精製水 全100ml 上記組成の点眼剤を調製した。Example 2 Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 8 COONa 0.24 Glycerin 2.3 NaOH Suitable amount → pH 7.5 Sterile purified water 100 ml All eye drops having the above composition were prepared.
この点眼剤はCH3(CH2)8COONaを含まないものに比べ
て、in Vitroでの透過性、点眼後の房水内濃度のいずれ
も有意に高かった。This eye drop had significantly higher permeability in vitro and higher concentration in the aqueous humor after instillation than those without CH 3 (CH 2 ) 8 COONa.
実施例３ 塩酸ブナゾシン 0.5g CH3(CH2)7SO3Na 0.26 グリセリン 2.3 NaOH 適量→pH7.5 滅菌精製水 全100ml 上記組成の点眼剤を調製した。Example 3 Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 7 SO 3 Na 0.26 Glycerin 2.3 NaOH proper amount → pH 7.5 sterilized purified water Total 100 ml An eye drop having the above composition was prepared.
この点眼剤はCH3(CH2)7SO3Naを含まないものに比べ
て、in Vitroでの透過性、点眼後の房水内濃度のいずれ
も有意に高かった。This eye drop had significantly higher permeability in vitro and higher concentration in the aqueous humor after instillation than those without CH 3 (CH 2 ) 7 SO 3 Na.
実施例４ 塩酸ブナゾシン 0.5g CH3(CH2)6COONa 0.2 リン酸1Na 0.2 リン酸2Na 2.0 NaCl 0.1g KCl 0.16 グリセリン 0.6 滅菌精製水 全100ml 上記組成の点眼剤を調製した。Example 4 Bunazosin hydrochloride 0.5 g CH 3 (CH 2 ) 6 COONa 0.2 Phosphoric acid 1 Na 0.2 Phosphoric acid 2 Na 2.0 NaCl 0.1 g KCl 0.16 Glycerin 0.6 Sterilized purified water Total 100 ml An eye drop having the above composition was prepared.
この点眼剤はCH3(CH2)6COONa及びリン酸塩を含まない
ものに比べて、in Vitroでの透過性、点眼後の房水内濃
度のいずれも有意に高かった。This eye drop had significantly higher permeability in vitro and higher concentration in aqueous humor after instillation than those without CH 3 (CH 2 ) 6 COONa and phosphate.
実施例５ 下記４種類の点眼剤を調製し、その角膜透過定数を求
めた。Example 5 The following four types of eye drops were prepared, and the corneal permeability constant thereof was determined.
結果を表３に示す。 Table 3 shows the results.
〈点眼剤の調製〉 点眼剤−１（本発明品） 塩酸ブナゾシンの添加量を0.1％、カプリル酸ナトリ
ウムの添加量を塩酸ブナゾシンに対して等モルにした以
外は実施例４の点眼剤と同様のもの。<Preparation of eye drops> Eye drops-1 (product of the present invention) Same as the eye drops of Example 4 except that the addition amount of bunazosin hydrochloride was 0.1% and the addition amount of sodium caprylate was equimolar to bunazosin hydrochloride. Things.
点眼剤−２（本発明品） 点眼剤−１からカプリル酸ナトリウムを除いたもの。Eye drops-2 (Product of the present invention) Eye drops-1 from which sodium caprylate is removed.
点眼剤−３（本発明品） 塩酸ブナゾシンの添加量を0.1％、カプリル酸ナトリ
ウムの添加量を塩酸ブナゾシンに対して等モルにした以
外は実施例１の点眼剤と同様のもの。Eye drops-3 (Product of the present invention) The same as the eye drops of Example 1 except that the amount of bunazosin hydrochloride added was 0.1% and the amount of sodium caprylate added was equimolar to bunazosin hydrochloride.
点眼剤−４（比較品） 点眼剤−３からカプリル酸ナトリウムを除いたもの。Eye drops-4 (comparative product) Eye drops-3 from which sodium caprylate is removed.
実施例６ 塩酸プラゾシン 0.05g CH3(CH2)6COONa 0.02 グリセリン 2.3g NaOH 適量→pH7.5 滅菌精製水 全100ml 上記組成の点眼液を調製した。 Example 6 Prazosin hydrochloride 0.05 g CH 3 (CH 2 ) 6 COONa 0.02 Glycerin 2.3 g NaOH proper amount → pH 7.5 sterilized purified water 100 ml An ophthalmic solution having the above composition was prepared.
第１図は実験例で用いたin Vitro角膜透過実験に用いた
装置の略示断面図、第２図は実験例２の結果を示すグラ
フ、第３図は実験例３の結果を示すグラフ、第４図は実
験例４の結果を示すグラフ、第５図は実験例６の結果を
示すグラフ、第６図は実験例７の結果を示すグラフであ
る。 1:セル 2:摘出角膜（家兎） 3:人工房水 4:実験液FIG. 1 is a schematic sectional view of an apparatus used in the in vitro corneal permeation experiment used in Experimental Example, FIG. 2 is a graph showing the result of Experimental Example 2, and FIG. 3 is a graph showing the result of Experimental Example 3. FIG. 4 is a graph showing the results of Experimental Example 4, FIG. 5 is a graph showing the results of Experimental Example 6, and FIG. 6 is a graph showing the results of Experimental Example 7. 1: Cell 2: Extracted cornea (rabbit) 3: Artificial aqueous humor 4: Experimental liquid
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 米国特許4197301（ＵＳ，Ａ) ─────────────────────────────────────────────────── --Continued front page (56) References US Patent 4197301 (US, A)
Claims (1)
酸、炭素数６〜10のアルキルスルホン酸、リン酸又はク
エン酸、或いはこれらの塩を配合してなるか、もしくは
プラゾシンに、炭素数６〜10の直鎖脂肪酸又は炭素数６
〜10のアルキルスルホン酸、或いはこれらの塩を配合し
てなる角膜透過促進点眼剤。1. Bunazosin is blended with a linear fatty acid having 6 to 10 carbon atoms, an alkylsulfonic acid having 6 to 10 carbon atoms, phosphoric acid or citric acid, or a salt thereof, or prazosin is mixed with carbon. Number 6-10 straight chain fatty acid or carbon number 6
A corneal penetration-enhancing eye drop comprising ~ 10 alkyl sulfonic acid or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62137921A JP2563336B2 (en) | 1987-06-01 | 1987-06-01 | Eye drops for promoting corneal penetration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62137921A JP2563336B2 (en) | 1987-06-01 | 1987-06-01 | Eye drops for promoting corneal penetration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63301822A JPS63301822A (en) | 1988-12-08 |
| JP2563336B2 true JP2563336B2 (en) | 1996-12-11 |
Family
ID=15209800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62137921A Expired - Lifetime JP2563336B2 (en) | 1987-06-01 | 1987-06-01 | Eye drops for promoting corneal penetration |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2563336B2 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2794022B2 (en) * | 1988-11-11 | 1998-09-03 | 三生製薬株式会社 | Transdermal preparation containing bunazosin or its salts |
| ATE96022T1 (en) * | 1989-08-03 | 1993-11-15 | Eisai Co Ltd | PROCESS FOR PHOTOSTABILIZATION OF EYE WASH SOLUTIONS. |
| JP4377052B2 (en) * | 1997-11-05 | 2009-12-02 | 千寿製薬株式会社 | Sustained eye drops |
| US6335335B2 (en) | 1997-11-05 | 2002-01-01 | Senju Pharmaceutical Co., Ltd. | Prolonged-action eye drop |
| FR2823441B1 (en) * | 2001-04-12 | 2004-09-10 | Thea Lab | MACROLIDE-BASED PHARMACEUTICAL COMPOSITION FOR LOCAL OPHTHALMOLOGY APPLICATION AND PROCESS FOR PREPARING THE SAME |
| US20020198209A1 (en) * | 2001-05-03 | 2002-12-26 | Allergan Sales Inc. | Compositions having enhanced pharmacokinetic characteristics |
| JP4933897B2 (en) | 2004-11-05 | 2012-05-16 | 千寿製薬株式会社 | Intraocular transfer-promoting aqueous eye drops |
| CN101495117B (en) | 2006-07-31 | 2012-08-15 | 千寿制药株式会社 | Aqueous liquid preparation containing amide compound |
| JP6917103B1 (en) * | 2021-05-17 | 2021-08-11 | 株式会社坪田ラボ | Eye drops for suppressing myopia |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4197301A (en) | 1978-10-16 | 1980-04-08 | Allergan Pharmaceuticals, Inc. | Topical ophthalmic use of Prazosin |
-
1987
- 1987-06-01 JP JP62137921A patent/JP2563336B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4197301A (en) | 1978-10-16 | 1980-04-08 | Allergan Pharmaceuticals, Inc. | Topical ophthalmic use of Prazosin |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63301822A (en) | 1988-12-08 |
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