WO2019124523A1 - FP作動薬とβ遮断薬を含有する緑内障治療剤 - Google Patents
FP作動薬とβ遮断薬を含有する緑内障治療剤 Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Definitions
- the present invention relates, in one aspect, a therapeutic agent for glaucoma, comprising an FP agonist as an active ingredient, which is administered in combination with a ⁇ blocker, wherein the FP agonist has the following formula
- the invention relates to an agent for treating glaucoma, which is a compound represented by (wherein all symbols are as defined below).
- Glaucoma is an eye disease characterized by visual impairment that causes temporary or permanent visual field loss and visual loss. It is caused by the optic nerve being compressed because the aqueous humor is accumulated due to the circulatory disturbance of the aqueous humor and the intraocular pressure is continuously increased. In the treatment of glaucoma, it is effective to reduce the intraocular pressure, and for example, drug treatment (eyedrops, oral medication, drip treatment), laser treatment, surgical treatment is given to lower the intraocular pressure.
- drug treatment eyedrops, oral medication, drip treatment
- laser treatment surgical treatment is given to lower the intraocular pressure.
- An FP agonist used as an active ingredient of the present invention is known as a pharmaceutical useful as a preventive and / or therapeutic agent for ocular diseases and the like (see Patent Document 1).
- 2-propanyl 4- ⁇ (3S, 5aR, 6R, 7R, 8aS) -6-[(1E, 3R) -4- (2,5-difluorophenoxy) -3-hydroxy-1-butene-1] -Yl] -7-hydroxyoctahydro-2H-cyclopenta [b] oxepin-3-yl ⁇ butanoate is known as Sepetaprost (International common name) (hereinafter sometimes abbreviated as Compound A) and is Development as a glaucoma treatment is in progress.
- Patent Document 1 describes Compound A as Example 16 (25), and a ⁇ blocker as an example of another drug for complementing and / or enhancing the preventive and / or therapeutic effect of glaucoma and the like on glaucoma Is described.
- An object of the present invention is to find an effective glaucoma treatment and provide it as a medicine.
- the present inventors can solve the above problems by the combination of FP agonist and ⁇ blocker (hereinafter sometimes abbreviated as the combination of the present invention). I found it.
- a therapeutic agent for glaucoma or ocular hypertension comprising an FP agonist as an active ingredient, which is administered in combination with a ⁇ -blocker or a pharmaceutically acceptable salt thereof, wherein said FP agonist
- the drug is 2-propanyl 4- ⁇ (3S, 5aR, 6R, 7R, 8aS) -6-[(1E, 3R) -4- (2,5-difluorophenoxy) -3-hydroxy-1-butene-1-l].
- [G] is a therapeutic agent for glaucoma or ocular hypertension which is -7-hydroxyoctahydro-2H-cyclopenta [b] oxepin-3-yl ⁇ butanoate, [2] The agent according to the above-mentioned [1], wherein the ⁇ -blocker is timolol, carteolol, levobnolol, betaxolol, niprazirol or befnolol. [3] The agent according to the above [1] or [2], wherein the beta blocker is timolol.
- a method of treating ocular hypertension comprising administering an effective amount of a beta blocker or a pharmaceutically acceptable salt thereof, a method of treating glaucoma or ocular hypertension, [12] 2-propanyl 4- ⁇ (3S, 5aR, 6R, 7R, 8aS) -6-, used in the treatment of glaucoma or ocular hypertension in combination with a beta blocker or a pharmaceutically acceptable salt thereof [(1E, 3R) -4- (2,5-Difluorophenoxy) -3-hydroxy-1-buten-1-yl] -7-hydroxyoctahydro-2H-cyclopenta [b] oxepin-3-yl ⁇ butanoate , [13] 2-propanyl 4- ⁇ (3S, 5aR) for the manufacture of a therapeutic agent for glaucoma or ocular hypertension characterized by being administered in combination with a ⁇ -blocker or a pharmaceutically acceptable salt thereof , 6R, 7R,
- the combination of the present invention is useful as a glaucoma therapeutic agent because it has an effect of enhancing the ocular pressure lowering action and maintaining the ocular pressure lowering action as compared with single administration of each drug.
- the FP agonist used in the combination of the present invention has the following formula described in WO 2011/01751
- alkyl groups include straight and branched ones.
- geometric isomers E form, Z form, cis form, trans form
- optical isomers R, S form, ⁇ , ⁇ configuration, etc.
- Enantiomers, diastereomers optically active substances having optical rotatory power (D, L, d, l isomers)
- polar bodies by chromatographic separation high polar bodies, low polar bodies
- equilibrium compounds rotamers, and the like
- optical isomers in the present invention may be not only 100% pure, but may contain less than 50% of other optical isomers.
- Example 1 Compound A is described in Example 1 ⁇ Example 2 ⁇ Example 3 ⁇ Example 4 ⁇ Example 5 ⁇ Example 6 ⁇ Example 7 ⁇ Example 8 ⁇ Example 9 described in International Publication WO2011 / 013651 ⁇ Example 10 (1) ⁇ Example 11 ⁇ Example 12 ⁇ Example 13 ⁇ Example 14 ⁇ Example 15 ⁇ Example 16 ⁇ Example 16 (25).
- the dose of the compound A used in the combination of the present invention varies depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc.
- eye drops preferably once per adult.
- the concentration is preferably 0.000001 to 5% (w / w), more preferably 0.00001 to 0.05% (w / w) once to several times a day (for example, 1 to 4 times) It may be applied.
- a ⁇ blocker is an agent that blocks any one of ⁇ -adrenoceptor, ⁇ 1, ⁇ 2 and ⁇ 3 receptors among sympathetic adrenergic receptors
- the drug is not particularly limited as long as it is a drug used for glaucoma treatment, for example, timolol (timolol), carteolol (certeolol), levobnolol (levobunolol), betaxolol (betaxolol), niprazirol (nipradilol), befunolol (befunolol), or those Pharmaceutically acceptable salts are included. Among them, timolol maleate is preferable.
- the dose of the ⁇ -blocker used in the combination of the present invention varies depending on the age, body weight, symptoms, treatment effect, administration method, treatment time, etc., but the dose approved for manufacturing as a pharmaceutical or lower dose than the dose Can be applied.
- a specific dose is, for timolol, 0.1 to 0.5% (w / v), preferably 0.25 to 0.5% (w / v).
- carteolol 0.1 to 2% (w / v), preferably 1 to 2% (w / v) can be mentioned.
- levobnolol 0.1 to 0.5% (w / v), preferably 0.25 to 0.5% (w / v) can be mentioned.
- the salt is preferably a pharmaceutically acceptable salt, and is preferably water-soluble.
- the pharmaceutically acceptable salt salts of alkali metals (potassium, sodium etc.), salts of alkaline earth metals (calcium, magnesium etc.), ammonium salts, pharmaceutically acceptable organic amines (tetramethyl ammonium, Triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) aminomethane, lysine, arginine, N-methyl-D-glucamine etc.), acid addition Salts (mineral acid salts (hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, nitrate etc.), organic acid salts (acetate, trifluoroacetate, lactate, tartrate) Oxalate, fumarate, maleate, benzoate, citrate, methane salts,
- ⁇ -blockers are all marketed compounds, so their toxicity is sufficiently low and they can be safely used as pharmaceuticals.
- both FP agonist and beta blocker are suitable dosage forms for treating the disease, for example, eye drops, eye ointments and the like, each of which is separate It does not matter even if it is a form.
- the combination of the present invention may be a separate preparation, and in consideration of medication compliance, a combination preparation containing both agents in appropriate amounts, such as combination eye drops and combination eye ointments, is also preferable.
- FP agonist and beta blocker when FP agonist and beta blocker are used in separate formulations, simultaneous administration and administration by time difference are included.
- administration by time difference means that FP agonist and ⁇ -blocker are separately administered at a fixed time, and FP agonist is administered first and ⁇ -blocker is administered later as its administration sequence Or the beta agonist may be given first and the FP agonist may be given later.
- the eye drops and eye ointments used in the combination of the present invention can be formulated using widely used techniques.
- an isotonic agent, a buffer, a pH adjuster, a solubilizer, a thickener, a stabilizer, a preservative, and the like can be appropriately added as additives.
- stable eye drops can also be obtained by adding a pH regulator, a thickener, a dispersant and the like and suspending the drug.
- the toxicity of the combination of the present invention is sufficiently low that it can be used safely as a pharmaceutical.
- One aspect of the disease to be treated by the combination of the present invention is glaucoma, hypertonia.
- glaucoma include acute angle closure glaucoma, chronic angle closure glaucoma, secondary angle closure glaucoma, primary open angle glaucoma, secondary open angle glaucoma, congenital glaucoma, normal pressure glaucoma, aqueous humor hyperglaucoma Can be mentioned.
- the combination of the present invention may further be used for (1) complementation and / or enhancement of therapeutic effect, (2) improvement of kinetics and absorption, reduction of dosage, and / or (3) reduction of side effects.
- other glaucoma therapeutic agents may be known as long as they are known, for example, sympathetic agonists ( ⁇ 2 agonists: for example, apraclonidine hydrochloride etc., ⁇ 2 agonists: for example dipivefrin hydrochloride etc.), parasympathetic nerve action Drugs (eg, pilocarpine hydrochloride, carbachol, deme potassium, ecothiofate or distigmine bromide, etc.), sympathetic agents (.alpha.1 blocker: eg, bunazosin hydrochloride etc.), prostaglandin drugs (eg, isopropyl unoprostone, latanoprost) , Bimatoprost, travopros
- glycerin blending formulations of glycerin and fructose or isosorbide, etc.,
- ROCK Rho kinase inhibitors
- NMDA antagonists e.g., NMDA antagonists, and the like.
- Biological Example 1 Compound A and ⁇ -blocker were used as test substances for lowering intraocular pressure .
- Compound A was prepared in a solution of 3 ⁇ g / mL using a vehicle (an aqueous solution containing 0.3 w / v% sodium citrate, 0.5 w / v% polysorbate 80, and 0.8 w / v% sodium chloride).
- a vehicle an aqueous solution containing 0.3 w / v% sodium citrate, 0.5 w / v% polysorbate 80, and 0.8 w / v% sodium chloride.
- timolol trade name: Timoputol (registered trademark) 0.5% eye drops, Santen Pharmaceutical Co., Ltd.
- the intraocular pressure of both eyes was measured about 1 hour before vehicle and test substance administration to a male dog (TOYO Beagle, 16 to 42 months old at the beginning of use) that had been sufficiently acclimatized in advance, and the intraocular pressure value before instillation and did. Thereafter, 30 ⁇ L each of the test substance or vehicle was instilled into the treated eyes, and the intraocular pressure of both eyes was measured about 2, 4, 6, 8 and 24 hours after the administration.
- Intraocular pressure was applied with 0.4% oxybuprocaine hydrochloride (BENOXYEL ® eye drop 0.4%, Santen Pharmaceutical Co., Ltd.), which is a local anesthetic agent, under a local pressure anesthesia with a pneumatic tonometer ( Measured with Model 30 Classic, Leicato). The measurement was performed until three consecutive stable values (a difference between measured values obtained within 0.5 mm Hg) were obtained. The average of the three measurements obtained was taken as an intraocular pressure value (mmHg) and displayed up to one decimal place.
- mmHg intraocular pressure value
- the value obtained by subtracting the intraocular pressure value at each measurement time from the test substance and the intraocular pressure value before administration of the vehicle was taken as the intraocular pressure fall width, and the value obtained by averaging the intraocular pressure fall width of each individual at each measurement time was taken as the average intraocular pressure fall width.
- the maximum value was taken as the maximum intraocular pressure decrease width.
- the average intraocular pressure fall width 24 hours after administration was taken as the intraocular pressure fall width 24 hours after administration.
- Table 1 when there are two drug names in the group name, it means the administration order, for example, the compound A- timolol group means that the compound A is administered to the same eye first, and timolol is administered thereafter. .
- the combination of the present invention is useful for treating glaucoma or ocular hypertension because it exerts a remarkable ocular hypotensive effect.
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Abstract
Description
[1] β遮断薬またはその薬学的に許容される塩と組み合わせて投与されることを特徴とするFP作動薬を有効成分として含む、緑内障または高眼圧症の治療剤であって、前記FP作動薬が2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートである緑内障または高眼圧症の治療剤、
[2] β遮断薬が、チモロール、カルテオロール、レボブノロール、ベタキソロール、ニプラジロール、またはベフノロールである前記[1]に記載の剤、
[3] β遮断薬が、チモロールである前記[1]または[2]に記載の剤、
[4] β遮断薬またはその薬学的に許容される塩と2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートが、別々または同時に投与されることを特徴とする前記[1]ないし[3]のいずれか一項に記載の剤、
[5] 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートとβ遮断薬またはその薬学的に許容される塩とを組み合わせて投与されることを特徴とする緑内障または高眼圧症の治療のための医薬組成物、
[6] β遮断薬が、チモロール、カルテオロール、レボブノロール、ベタキソロール、ニプラジロール、またはベフノロールである前記[5]に記載の医薬組成物、
[7] β遮断薬が、チモロールである前記[5]または[6]に記載の医薬組成物、
[8] 点眼剤または眼軟膏である前記[5]ないし[7]のいずれか一項に記載の医薬組成物、
[9] 配合剤である前記[5]ないし[8]のいずれか一項に記載の医薬組成物、
[10] 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの有効量をβ遮断薬またはその薬学的に許容される塩と組み合わせて、緑内障または高眼圧症の治療を必要とする患者に、別々にまたは同時に投与することを特徴とする緑内障または高眼圧症の治療方法、
[11] 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの有効量を、緑内障または高眼圧症の治療を必要とする患者に投与することを特徴とする緑内障または高眼圧症の治療方法であって、当該方法はβ遮断薬またはその薬学的に許容される塩の有効量を投与することをさらに含む緑内障または高眼圧症の治療方法、
[12] β遮断薬またはその薬学的に許容される塩と組み合わせて緑内障または高眼圧症の治療に使用される、2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアート、
[13] β遮断薬またはその薬学的に許容される塩と組み合わせて投与されることを特徴とする緑内障または高眼圧症の治療剤の製造のための、2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの使用等の実施態様が挙げられる。
本発明の組み合わせに用いられるFP作動薬は、一態様において、国際公開第2011/013651号に記載された下記式
本発明において、β遮断薬は、交感神経のアドレナリン受容体のうち、β-アドレナリン受容体、β1、β2およびβ3の各受容体のいずれかを遮断する薬剤であって、緑内障治療に用いられる薬剤であれば特に限定されないが、例えば、チモロール(timolol)、カルテオロール(certeolol)、レボブノロール(levobunolol)、ベタキソロール(betaxolol)、ニプラジロール(nipradilol)、ベフノロール(befunolol)、またはそれらの薬学的に許容される塩が挙げられる。なかでも、チモロールマレイン酸塩が好ましい。
本発明の組み合わせの毒性は十分に低いものであり、医薬品として安全に使用することができる。
本発明の組み合わせによって治療される疾患の一態様として、緑内障、高眼圧症が挙げられる。緑内障としては、例えば、急性閉塞隅角緑内障、慢性閉塞隅角緑内障、続発閉塞隅角緑内障、原発開放隅角緑内障、続発開放隅角緑内障、先天性緑内障、正常眼圧緑内障、房水産生過多緑内障が挙げられる。
本発明において、他の緑内障治療剤としては、公知のものであればよく、例えば、交感神経作動薬(α2アゴニスト:例えば、塩酸アプラクロニジン等、β2アゴニスト:例えば、塩酸ジピベフリン等)、副交感神経作動薬(例えば、塩酸ピロカルピン、カルバコール、デメカリウム、エコチオフェートまたは臭化ジスチグミン等)、交感神経抑制薬(α1ブロッカー:例えば、塩酸ブナゾシン等)、プロスタグランジン系薬物(例えば、イソプロピルウノプロストン、ラタノプロスト、ビマトプロスト、トラヴォプロスト、EP2アゴニスト、EP4アゴニストまたはDPアゴニスト等)、炭酸脱水酵素阻害薬(例えば、アセタゾラミド、ジクロフェナミド、メタゾラミド、塩酸ドルゾラミド、またはブリンゾラミド等)、高張浸透圧薬(例えば、グリセリン、グリセリンおよび果糖の配合製剤、またはイソソルビド等)、ROCK(Rhoキナーゼ)阻害薬(例えば、Y-27632等)、NMDA拮抗薬が挙げられる。
被験物質として、化合物Aおよびβ遮断薬を用いた。化合物Aは、媒体(0.3w/v%クエン酸ナトリウム、0.5w/v%ポリソルベート80、および0.8w/v%塩化ナトリウムを含む水溶液)を用いて3μg/mLの溶液を調製した。β遮断薬として、チモロール(商品名:チモプトール(登録商標)0.5%点眼液、参天製薬株式会社)を使用した。
Claims (13)
- β遮断薬またはその薬学的に許容される塩と組み合わせて投与されることを特徴とするFP作動薬を有効成分として含む、緑内障または高眼圧症の治療剤であって、前記FP作動薬が2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートである緑内障または高眼圧症の治療剤。
- β遮断薬が、チモロール、カルテオロール、レボブノロール、ベタキソロール、ニプラジロール、またはベフノロールである請求項1に記載の剤。
- β遮断薬が、チモロールである請求項1または2に記載の剤。
- β遮断薬またはその薬学的に許容される塩と2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートが、別々または同時に投与されることを特徴とする請求項1ないし3のいずれか一項に記載の剤。
- 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートとβ遮断薬またはその薬学的に許容される塩とを組み合わせて投与されることを特徴とする緑内障または高眼圧症の治療のための医薬組成物。
- β遮断薬が、チモロール、カルテオロール、レボブノロール、ベタキソロール、ニプラジロール、またはベフノロールである請求項5に記載の医薬組成物。
- β遮断薬が、チモロールである請求項5または6に記載の医薬組成物。
- 点眼剤または眼軟膏である請求項5ないし7のいずれか一項に記載の医薬組成物。
- 配合剤である請求項5ないし8のいずれか一項に記載の医薬組成物。
- 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの有効量をβ遮断薬またはその薬学的に許容される塩と組み合わせて、緑内障または高眼圧症の治療を必要とする患者に、別々にまたは同時に投与することを特徴とする緑内障または高眼圧症の治療方法。
- 2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの有効量を、緑内障または高眼圧症の治療を必要とする患者に投与することを特徴とする緑内障または高眼圧症の治療方法であって、当該方法はβ遮断薬またはその薬学的に許容される塩の有効量を投与することをさらに含む緑内障または高眼圧症の治療方法。
- β遮断薬またはその薬学的に許容される塩と組み合わせて緑内障または高眼圧症の治療に使用される、2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアート。
- β遮断薬またはその薬学的に許容される塩と組み合わせて投与されることを特徴とする緑内障または高眼圧症の治療剤の製造のための、2-プロパニル 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-ジフルオロフェノキシ)-3-ヒドロキシ-1-ブテン-1-イル]-7-ヒドロキシオクタヒドロ-2H-シクロペンタ[b]オキセピン-3-イル}ブタノアートの使用。
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AU2018390274A AU2018390274C1 (en) | 2017-12-21 | 2018-12-20 | Therapeutic agent for glaucoma comprising FP agonist and β blocker |
CA3085747A CA3085747A1 (en) | 2017-12-21 | 2018-12-20 | Therapeutic agent for glaucoma comprising fp agonist and .beta.-blocker |
MX2020006429A MX2020006429A (es) | 2017-12-21 | 2018-12-20 | Agente terapeutico para el glaucoma que comprende un agonista de fp y un bloqueador beta. |
SG11202005620QA SG11202005620QA (en) | 2017-12-21 | 2018-12-20 | THERAPEUTIC AGENT FOR GLAUCOMA COMPRISING FP AGONIST AND ß BLOCKER |
CN201880080852.2A CN111479567B (zh) | 2017-12-21 | 2018-12-20 | 包含FP激动剂和β-阻断剂的青光眼的治疗剂 |
EA202091523A EA202091523A1 (ru) | 2017-12-21 | 2018-12-20 | Терапевтический агент для лечения глаукомы, содержащий агонист fp-рецепторов и -блокатор |
EP18891086.3A EP3730137B1 (en) | 2017-12-21 | 2018-12-20 | Therapeutic agent for glaucoma comprising an fp agonist and timolol |
JP2019560578A JP7247894B2 (ja) | 2017-12-21 | 2018-12-20 | FP作動薬とβ遮断薬を含有する緑内障治療剤 |
BR112020012521-0A BR112020012521A2 (pt) | 2017-12-21 | 2018-12-20 | agente terapêutico para glaucoma compreendendo agonista de fp e beta-bloqueador |
KR1020207016945A KR20200102435A (ko) | 2017-12-21 | 2018-12-20 | FP 작동약과 β 차단약을 함유하는 녹내장 치료제 |
US16/954,416 US20210085636A1 (en) | 2017-12-21 | 2018-12-20 | THERAPEUTIC AGENT FOR GLAUCOMA COMPRISING FP AGONIST AND ß BLOCKER |
PH12020550862A PH12020550862A1 (en) | 2017-12-21 | 2020-06-11 | THERAPEUTIC AGENT FOR GLAUCOMA COMPRISING FP AGONIST AND á-BLOCKER |
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