Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
  • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0048—Eye, e.g. artificial tears
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
  • A61P27/06—Antiglaucoma agents or miotics

Definitions

• the present invention relates to a prophylactic and/or therapeutic agent containing isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• Glaucoma is an eye disease in which an elevated intraocular pressure due to various causes may damage the tissues (retina, optic nerve, and the like) inside the eyeball and lead to visual loss.
• intraocular pressure-lowering therapies have been employed as treatment methods for glaucoma, and representative intraocular pressure-lowering therapies include drug therapies, laser therapies, surgical therapies, and the like.
• a treatment of rapidly lowering the greatly elevated intraocular pressure has been conducted by intravenous administration, oral administration, or the like of acetazolamide before radical treatment such as iridotomy.
• this treatment is sufficient in terms of safety and efficacy, and there has been a demand for a new drug therapy which is safer, and which lowers the greatly elevated intraocular pressure more rapidly.
• Isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate is a compound represented by the following formula (1) and described in Patent Literature 1 as one of the numerous pyridylaminoacetic acid compounds:
• Patent Literature 2 EP2 agonist action
• Patent Literature 1 EP2 agonist action
• Patent Literatures 3 and 4 state that a combination of the compound represented by the above-described formula (1) with another therapeutic agent for glaucoma such as timolol increases the intraocular pressure-lowering activity. Note that the entire contents described in Patent Literatures 1 to 4 are incorporated herein by reference.
• An object of the present invention is to find a new medicinal use of the above-described compound represented by the formula (1) or a salt thereof.
• the present inventors have conducted intensive studies, and found that isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof (hereinafter, also referred to as “the present compound”) lowers a greatly elevated intraocular pressure safely and rapidly. This finding has led to the completion of the present invention.
• the present invention relates to the following.
• a prophylactic and/or therapeutic agent for a disease involving a greatly elevated intraocular pressure comprising isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• the disease involving a greatly elevated intraocular pressure is acute primary angle closure, primary angle closure glaucoma, secondary angle closure glaucoma, or acute intraocular pressure elevation.
• prophylactic and/or therapeutic agent according to anyone of the above-described items [1] to [3], which does not comprise any other prophylactic and/or therapeutic agent for glaucoma or ocular hypertension than isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• An eye drop comprising the prophylactic and/or therapeutic agent according to any one of the above-described items [1] to [4].
• An eye drop comprising isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof according to the above-described item [6] or [7].
• a method for preventing and/or treating a disease involving a greatly elevated intraocular pressure comprising administering isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof to patients with said disease which has to be prevented and/or treated.
• the method according to the above-described item [14] wherein the disease involving a greatly elevated intraocular pressure is acute primary angle closure, primary angle closure glaucoma, secondary angle closure glaucoma, or acute intraocular pressure elevation.
• prophylactic and/or therapeutic agent of the present invention is simply referred to as “therapeutic agent”, unless otherwise noted.
• Isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof contained in the therapeutic agent of the present invention can be produced according to the method described in United States Patent Application Publication No. 2012/0190852 (Patent Literature 1), an ordinary method in the technical field, or the like.
• the salt of isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate contained in the therapeutic agent of the present invention is not particularly limited, as long as the salt is pharmacologically acceptable.
• the salt may be an inorganic acid salt such as hydrochloric acid salt, hydrobromic acid salt, hydroiodic acid salt, nitric acid salt, sulfuric acid salt, or phosphoric acid salt; an organic acid salt such as acetic acid salt, trifluoroacetic acid salt, benzoic acid salt, oxalic acid salt, malonic acid salt, succinic acid salt, maleic acid salt, fumaric acid salt, tartaric acid salt, citric acid salt, methanesulfonic acid salt, ethanesulfonic acid salt, trifluoromethanesulfonic acid salt, benzenesulfonic acid salt, p-toluenesulfonic acid salt, glutamic acid sal, or aspartic acid salt; or the like.
• the salt is preferably a hydrochloric acid salt or a trifluoroacetic acid salt.
• the content of isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or the salt thereof in the therapeutic agent of the present invention is not particularly limited.
• the lower limit of the content is preferably 0.0003% (w/v), more preferably 0.001 (w/v), further preferably 0.0013% (w/v), and particularly preferably 0.0015% (w/v).
• the upper limit of the content is preferably 0.03% (w/v), more preferably 0.01% (w/v), further preferably 0.005% (w/v), particularly preferably 0.003% (w/v), and especially preferably 0.0027% (w/v). More specifically, the content is preferably 0.0003 to 0.03% (w/v), more preferably 0.001 to 0.01% (w/v), further preferably 0.001 to 0.005% (w/v), particularly preferably 0.001 to 0.003% (w/v), especially preferably 0.0013 to 0.003% (w/v), and still further preferably 0.0015 to 0.0027% (w/v).
• the content is preferably 0.0010% (w/v), 0.0011% (w/v), 0.0012% (w/v), 0.0013% (w/v), 0.0014% (w/v), 0.0015% (w/v), 0.0016% (w/v), 0.0017% (w/v), 0.0018% (w/v), 0.0019% (w/v), 0.0020% (w/v), 0.0021% (w/v), 0.0022% (w/v), 0.0023% (w/v), 0.0024% (w/v), 0.0025% (w/v), 0.0026% (w/v), 0.0027% (w/v), 0.0028% (w/v), 0.0029% (w/v), 0.0030% (w/v), 0.005% (w/v), 0.01% (w/v), or 0.03% (w/v), or the content is preferably in a range having an upper limit or a lower limit selected from any of these amounts.
• % (w/v) means the mass (g) of an active ingredient (the present compound here) or an additive (surfactant or the like) contained per 100 mL of the eye drop.
• 0.01% (w/v) of the present compound means that the content of the present compound per 100 mL of the eye drop is 0.01 g.
• this content means that the content of isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate, which is the free form of the salt, is within the above-described range.
• additives can be used in the therapeutic agent of the present invention.
• a surfactant for example, a buffering agent, a tonicity adjusting agent, a stabilizer, an antiseptic agent, an antioxidant, a high-molecular weight polymer, and the like can be added.
• a surfactant usable as an additive for pharmaceuticals can be blended, as appropriate.
• surfactant examples include polyoxyethylene castor oils, polyoxyethylene hardened castor oils, polyoxyethylene sorbitan fatty acid esters, vitamin E TPGS, polyoxyethylene fatty acid esters, polyoxyethylene polyoxypropylene glycols, sucrose fatty acid esters, and the like.
• polyoxyethylene castor oils various polyoxyethylene castor oils having different degrees of polymerization of ethylene oxide can be used.
• the degree of polymerization of ethylene oxide is preferably 5 to 100, more preferably 20 to 50, particularly preferably 30 to 40, and most preferably 35.
• Specific examples of the polyoxyethylene castor oils include polyoxyl 5 castor oil, polyoxyl 9 castor oil, polyoxyl 15 castor oil, polyoxyl 35 castor oil, polyoxyl 40 castor oil, and the like, and polyoxyl 35 castor oil is the most preferable.
• polyoxyethylene hardened castor oils various polyoxyethylene hardened castor oils having different degrees of polymerization of ethylene oxide can be used.
• the degree of polymerization of ethylene oxide is preferably 10 to 100, more preferably 20 to 80, particularly preferably 40 to 70, and most preferably 60.
• Specific examples of the polyoxyethylene hardened castor oils include polyoxyethylene hardened castor oil 10, polyoxyethylene hardened castor oil 40, polyoxyethylene hardened castor oil 50, polyoxyethylene hardened castor oil 60, and the like, and polyoxyethylene hardened castor oil 60 is the most preferable.
• polyoxyethylene sorbitan fatty acid esters include polysorbate 80, polysorbate 60, polysorbate 40, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan trioleate, polysorbate 65, and the like, and polysorbate 80 is the most preferable.
• Vitamin E TPGS is also referred to as tocopherol polyethylene glycol 1000 succinate.
• the polyoxyethylene fatty acid esters include polyoxyl 40 stearate, and the like.
• the polyoxyethylene polyoxypropylene glycols include polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (20) polyoxypropylene (20) glycol, and the like.
• sucrose fatty acid esters include sucrose stearate and the like.
• the content of the surfactant can be adjusted, as appropriate, according to the type of the surfactant and the like.
• the lower limit is preferably 0.001% (w/v), more preferably 0.01% (w/v), further preferably 0.1% (w/v), particularly preferably 0.5% (w/v), and most preferably 0.8% (w/v).
• the upper limit is preferably 10% (w/v), more preferably 5% (w/v), further preferably 4% (w/v), particularly preferably 3% (w/v)), and most preferably 2% (w/v).
• the content is preferably 0.001 to 10% (w/v), more preferably 0.01 to 5% (w/v), further preferably 0.1 to 4% (w/v), particularly preferably 0.5 to 3% (w/v), and most preferably 0.8 to 2% (w/v).
• a buffering agent usable as an additive for pharmaceuticals can be blended, as appropriate.
• buffering agent examples include phosphoric acid, salts thereof, boric acid, salts thereof, citric acid, salts thereof, acetic acid, salts thereof, carbonic acid, salts thereof, tartaric acid, salts thereof, ⁇ -aminocaproic acid, trometamol, and the like.
• the salts of phosphoric acid include sodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and the like;
• the salts of boric acid include borax, sodium borate, potassium borate, and the like;
• the salts of citric acid include sodium citrate, disodium citrate, trisodium citrate, and the like;
• the salts of acetic acid include sodium acetate, potassium acetate, and the like;
• the salts of carbonic acid include sodium carbonate, sodium hydrogen carbonate, and the like;
• the salts of tartaric acid include sodium tartrate, potassium tartrate, and the like.
• boric acid, salts thereof, citric acid, and salts thereof are preferable.
• the content of the buffering agent can be adjusted, as appropriate, according to the type of the buffering agent and the like, and is preferably 0.001 to 10% (w/v), more preferably 0.01 to 5% (w/v), further preferably 0.1 to 3% (w/v), and most preferably 0.2 to 2% (w/v).
• a tonicity adjusting agent usable as an additive for pharmaceuticals can be blended, as appropriate.
• tonicity adjusting agent examples include ionic tonicity adjusting agents, nonionic tonicity adjusting agents, and the like.
• the ionic tonicity adjusting agents include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like.
• the nonionic tonicity adjusting agents include glycerin, propylene glycol, sorbitol, mannitol, and the like.
• the content of tonicity adjusting agent can be adjusted, as appropriate, according to the type of the tonicity adjusting agent and the like, and is preferably 0.01 to 10% (w/v), more preferably 0.02 to 7% (w/v), further preferably 0.1 to 5% (w/v), particularly preferably 0.5 to 4% (w/v), and most preferably 0.8 to 3% (w/v).
• a stabilizer usable as an additive for pharmaceuticals can be blended, as appropriate.
• the stabilizer examples include edetic acid, monosodium edetate, disodium edetate, tetrasodium edetate, sodium citrate, and the like, and disodium edetate is particularly preferable.
• the sodium edetates may be hydrates.
• an antiseptic agent usable as an additive for pharmaceuticals can be blended, as appropriate.
• the antiseptic agents include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, sorbic acid, potassium sorbate, methyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, and the like.
• the content of the antiseptic agent can be adjusted, as appropriate, according to the type of the antiseptic agent and the like, and is preferably 0.0001 to 1% (w/v), more preferably 0.0005 to 0.1% (w/v), further preferably 0.001 to 0.05% (w/v), and most preferably 0.005 to 0.010% (w/v).
• an antioxidant usable as an additive for pharmaceuticals can be blended, as appropriate.
• antioxidants examples include ascorbic acid, tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, sodium erythorbate, propyl gallate, sodium sulfite, and the like.
• the content of the antioxidant can be adjusted, as appropriate, according to the type of the antioxidant and the like, and is preferably 0.0001 to 1% (w/v), more preferably 0.0005 to 0.1% (w/v), and most preferably 0.001 to 0.05% (w/v).
• a high-molecular weight polymer usable as an additive for pharmaceuticals can be blended, as appropriate.
• Examples of the high-molecular weight polymer include methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxy methyl cellulose sodium salt, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, cellulose acetate phthalate, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, polyethylene glycol, and the like.
• the content of the high-molecular weight polymer can be adjusted, as appropriate, according to the type of the high-molecular weight polymer and the like, and is preferably 0.001 to 5% (w/v), more preferably 0.01 to 1% (w/v), and most preferably 0.1 to 0.5% (w/v).
• the pH of the therapeutic agent of the present invention is preferably 4.0 to 8.0, more preferably 4.5 to 7.5, particularly preferably 5.0 to 7.0, and most preferably 5.5 to 6.5.
• a pH adjusting agent for adjusting the pH may be added such as hydrochloric acid, phosphoric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, or the like.
• the therapeutic agent of the present invention can be stored in containers produced from various materials.
• a container made of polyethylene, polypropylene, or the like can be used.
• the therapeutic agent of the present invention is preferably stored in a polyethylene container from the viewpoints of the ease of instillation (hardness of the container), the stability of the present compound, and the like.
• the dosage form of the therapeutic agent of the present invention is not particularly limited, as long as the dosage form is usable for pharmaceuticals.
• the dosage form may be an eye drop, an ophthalmic injection, an ophthalmic ointment, or the like, and is particularly preferably an eye drop.
• These dosage forms of these drugs can be produced according to ordinary methods in the technical field.
• a solvent or dispersion medium used when the therapeutic agent of the present invention is a liquid agent is preferably water.
• the therapeutic agent of the present invention may contain or may be used in combination with one or more, preferably 1 to 3, and more preferably 1 or 2 prophylactic and/or therapeutic agents for glaucoma or ocular hypertension other than the present compound.
• the other prophylactic and/or therapeutic agents for glaucoma or ocular hypertension are not particularly limited.
• the other prophylactic and/or therapeutic agents are preferably therapeutic agents for glaucoma and the like which are commercially available or under development, more preferably commercially available therapeutic agents for glaucoma and the like, and particularly preferably commercially available therapeutic agents for glaucoma and the like which have different mechanisms of action from that of the present compound.
• the other prophylactic and/or therapeutic agents include nonselective sympathomimetics, ⁇ 2 receptor agonists, ⁇ 1 receptor blockers, ⁇ receptor blockers, parasympathomimetics, carbonic anhydrase inhibitors, prostaglandins, Rho kinase inhibitors, and the like.
• a specific example of the nonselective sympathomimetics is dipivefrine.
• Specific examples of the ⁇ 2 receptor agonists include brimonidine and apraclonidine.
• a specific example of the ⁇ 1 receptor blocker is bunazosin.
• Specific examples of the ⁇ receptor blockers include timolol, befunolol, carteolol, nipradilol, betaxolol, levobunolol, and metipranolol.
• a specific example of the parasympathomimetics is pilocarpine.
• Specific examples of the carbonic anhydrase inhibitors include dorzolamide, brinzolamide, and acetazolamide.
• prostaglandins include latanoprost, isopropyl unoprostone, bimatoprost, and travoprost.
• Rho kinase inhibitors is ripasudil.
• the therapeutic agent of the present invention does not contain any other prophylactic and/or therapeutic agent for glaucoma or ocular hypertension than isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• the therapeutic agent of the present invention is not used in combination with any other prophylactic and/or therapeutic agent for glaucoma or ocular hypertension than isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate or a salt thereof.
• the therapeutic agent of the present invention can be administered orally or parenterally. No special technique is required to prepare pharmaceutical preparations of the therapeutic agent, and the pharmaceutical preparations can be prepared by using commonly used techniques.
• the dosage forms for the administration include eye drops, ophthalmic ointments, injections, tablets, capsules, granules, powders, and the like, and eye drops are preferable.
• the usage of the therapeutic agent of the present invention is not particularly limited, as long as the usage is enough to achieve a desired medicinal effect.
• a suitable usage can be selected, as appropriate, according to symptoms of the disease, the age and body weight of the patient, the dosage form of the agent, and the like.
• 1 to 5 drops, preferably 1 to 3 drops, more preferably 1 to 2 drops, and particularly preferably 1 drop of the therapeutic agent of the present invention can be instilled 1 to 4 times a day, preferably 1 to 3 times a day, more preferably 1 to 2 times a day, and particularly preferably once a day, every day to every week. It is preferable to instill one drop of the therapeutic agent of the present invention once a day, every day.
• 1 drop is generally approximately 0.01 to approximately 0.1 mL, preferably approximately 0.015 to approximately 0.07 mL, more preferably approximately 0.02 to approximately 0.05 mL, and particularly preferably approximately 0.03 mL.
• the therapeutic agent of the present invention is a prophylactic and/or therapeutic agent for a disease involving a greatly elevated intraocular pressure, and is a pharmaceutical preparation used to rapidly reduce or lower the intraocular pressure.
• the “disease involving a greatly elevated intraocular pressure” refers to a disease with an intraocular pressure in a range of, for example, from 25 to 100 mmHg, preferably from 25 to 80 mmHg, more preferably from 30 to 80 mmHg, and further preferably from 40 to 80 mmHg. For such a disease, it is necessary to rapidly lower the intraocular pressure.
• the “greatly elevated intraocular pressure” which has to be treated or prevented by the present invention includes not only the so-called acute ocular hypertension state as in the case where the intraocular pressure is rapidly elevated to the above-described high intraocular pressure range in several weeks, several days, or several hours, but also the so-called chronic ocular hypertension state where the above-described greatly elevated intraocular pressure is reached over a long period of several months or several years.
• the phrase “rapidly reduce the intraocular pressure” or “rapidly lower the intraocular pressure” means that the intraocular pressure is reduced or lowered to a normal level, for example, in a range from 10 to 25 mmHg and preferably in a range from 10 to 20 mmHg within, for example, 24 hours, preferably 12 hours, more preferably 6 hours, further preferably 4 hours, and especially preferably 2 hours.
• a reduction in intraocular pressure of ⁇ 1 to ⁇ 90 mmHg preferably ⁇ 5 to ⁇ 80 mmHg, more preferably ⁇ 7 to ⁇ 70 mmHg, further preferably ⁇ 10 to ⁇ 70 mmHg, and most preferably ⁇ 10 to ⁇ 60 mmHg, for example, within 6 hours
• a negative value of “ ⁇ 10 mmHg” means that the intraocular pressure is reduced by 10 mmHg from that before treatment.
• examples of the “disease involving a greatly elevated intraocular pressure” include acute primary angle closure, primary angle closure glaucoma, secondary angle closure glaucoma, and acute intraocular pressure elevation such as that caused by inflammation such as uveitis.
• Patients with the above-described disease which has to be prevented and/or treated include humans and non-human animals, and, especially, humans and non-human mammals.
• the blended amount of each component is an amount in 100 mL of the pharmaceutical preparation.
• the present compound A means isopropyl (6- ⁇ [4-(pyrazol-1-yl)benzyl](pyridin-3-ylsulfonyl)aminomethyl ⁇ pyridin-2-ylamino)acetate.
• Table 1 shows the average intraocular pressure reduction (relative to the initial intraocular pressure) of each of the treated groups at 2 hours, 4 hours, and 6 hours after the administration.
• Example 1- ⁇ 16.2 ⁇ 19.3 ⁇ 19.7 treated group Comparative ⁇ 7.4 ⁇ 8.9 ⁇ 9.3
• the “negative sign ( ⁇ )” has such a meaning that, for example, in the case of ⁇ 1.0, the intraocular pressure was reduced by 1.0 from the initial intraocular pressure.
• the intraocular pressure-lowering activity of the present compound A of Example 1 was larger than that in the latanoprost-treated group of Comparative Example 1, and the present compound A of Example 1 exhibited an excellent intraocular pressure-lowering activity no later than 2 hours after the administration.

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• 2016
  • 2016-07-07 JP JP2017527490A patent/JP7032134B2/ja active Active
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