WO1996004911A1 - Method of preventing and treating ophthalmic inflammation and/or wound - Google Patents
Method of preventing and treating ophthalmic inflammation and/or wound Download PDFInfo
- Publication number
- WO1996004911A1 WO1996004911A1 PCT/JP1995/001570 JP9501570W WO9604911A1 WO 1996004911 A1 WO1996004911 A1 WO 1996004911A1 JP 9501570 W JP9501570 W JP 9501570W WO 9604911 A1 WO9604911 A1 WO 9604911A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- active ingredient
- carbostyril
- salts
- ophthalmic
- drug containing
- Prior art date
Links
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- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000000826 nictitating membrane Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- CMHHMUWAYWTMGS-UHFFFAOYSA-N oxybuprocaine Chemical compound CCCCOC1=CC(C(=O)OCCN(CC)CC)=CC=C1N CMHHMUWAYWTMGS-UHFFFAOYSA-N 0.000 description 1
- PRGUDWLMFLCODA-UHFFFAOYSA-N oxybuprocaine hydrochloride Chemical compound [Cl-].CCCCOC1=CC(C(=O)OCC[NH+](CC)CC)=CC=C1N PRGUDWLMFLCODA-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- DCNLOVYDMCVNRZ-UHFFFAOYSA-N phenylmercury(.) Chemical class [Hg]C1=CC=CC=C1 DCNLOVYDMCVNRZ-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 235000011083 sodium citrates Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- 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
- A61K31/47—Quinolines; Isoquinolines
Definitions
- This invention relates to a method of preventing and treating ophthalmic inflammation and/or wound.
- R 1 and R 2 respectively indicate a lower alkyl group, and a bond between carbons of a carbostyril skeleton at the 3- and 4-positions indicates a single bond or a double bond
- salts thereof are effective as bronchodilators, peripheral vasodilators and antihypertensive drugs.
- U.S. Patent No. 4,322,425 there is disclosed that the above compounds are effective as remedies for glaucoma.
- Japanese Laid-Open Patent Publication No. 64-52727 there is disclosed that the above compounds are useful as antiallergic eye drops.
- the inventors have intensively studied about the carbostyril derivatives represented by the formula (1) or salts thereof.
- the carbostyril derivatives or salts thereof particularly 8- hydroxy-5-(l-hydroxy-2-isopropylaminobutyl)carbostyril hydrochloride accelerate the growth of various ophthalmic tissue cells such as ectocorneal cells, conjunctival cells, keratocytes, corneaendothelial cells, scleral fibroblasts, etc., and inhibit the destruction of the blood-aqueous humor shelf or the increase of the thickness of the cornea, whereby they are effective for various ophthalmic inflammations and/or wounds which are not related to allergy.
- various ophthalmic tissue cells such as ectocorneal cells, conjunctival cells, keratocytes, corneaendothelial cells, scleral fibroblasts, etc.
- this invention provides a preventive and a remedy for ophthalmic inflammation and/or wound, which comprises carbostyril derivatives represented by the formula (1) or salts thereof, particularly 8-hydroxy-5-(l-hydroxy-2- isopropylaminobutyl)carbostyril hydrochloride as an active ingredient.
- the preventive and remedy for ophthalmic inflammation and/or wound of this invention can be suitably used for ophthalmic inflammations and/or wounds other than allergic ophthalmic diseases, for example, blepharitis, conjunctivitis, keratitis, scleritis, episcleritis, uveitis of anterior eye part, postoperative inflammation, chronic conjunctivitis, vernal conjunctivitis, lamellar keratitis, blepharitis marginalis, acute conjunctivitis, secretory epiphora, herpes corneae, prevention of corneal xerosis and protection of corneal disorder during an ophthalmic operation, intraocular irrigation (perfusion) and ablution upon ophthalmic operation (e.g.
- Fig. 1 is a graph illustrating the results of the pharmacological test 1.
- Fig. 2 is a graph illustrating the results of the pharmacological test 2.
- Fig. 3 is a graph illustrating the results of the pharmacological test 3.
- Fig. 4 is a graph illustrating the results of the pharmacological test 4. ⁇ Best Mode for Carrying Out the Invention>
- the lower alkyl group represented by R A and R ⁇ include a straight- or branched-chain alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl and the like.
- a compound containing an acid group can form a salt with a pharmacologically acceptable basic compound.
- the basic compound include metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc. ; alkali metal carbonates or bicarbonates such as sodium carbonate, sodium bicarbonate, etc.; alkali metal alcoholates such as sodium methylate, potassium ethylate, etc.
- a compound having a basic group can form a salt easily with a pharmacologically acceptable acid.
- the acid examples include inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc.; organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzole acid, etc.
- inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc.
- organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzole acid, etc.
- acid addition salts are particularly preferred.
- Examples of the carbostyril derivative represented by the formula (1) include the followings.
- the preventive and remedy for ophthalmic inflammation and/or wound of this invention are prepared into a suitable dosage unit form by mixing the carbostyril derivative represented by the formula (1) or a salt thereof with a conventional carrier for ophthalmic preparation.
- a dosage unit form various normal forms can be optionally used. Examples of the form for local administration include ophthalmic ointment, eye drop, intraocular irrigating solution, etc., and examples of the form for general administration include tablet, granule, injection, etc. It is particularly preferred that the drug of this invention is prepared into the form of eye drop or intraocular irrigating solution.
- the dose of the drug of this invention is not specifically limited, and it is advantageous that an amount of the active ingredient in the drug may be normally administered to an adult patient 2 to 3 times per day with a dairy dose of 0.01 to 0.5 mg, preferably 0.05 to 0.1 mg. Further, it is preferred that an amount of the active ingredient in the drug is normally within a range of 0.04 to 2 % by weight.
- the drug of this invention can be produced using a normal method. For example, it is produced by mixing the carbostyril derivative represented by the formula (1) or a salt thereof as the active ingredient with a suitable base, and adding excipients, if necessary. In case of ophthalmic ointment, eye drop, injection, etc., the drug of this invention is produced by subjecting to an additional sterilization treatment.
- the base to be used may be suitably selected according to the form of the drug.
- conventional emulsifiable bases, water-soluble bases, suspending bases, etc. can be used.
- Typical examples of the base include white vaseline, purified lanolin, liquid paraffin and the like.
- sterilized distilled water can be typically used as the base.
- solubilizers can also be blended in the drug of this invention.
- solubilizer include polyoxyethylene glycol ethers such as sodium carboxymethyl cellulose, polyoxyethylene lauryl ether, polyoxyethylene oleyl ether, etc.; polyoxyethylene fatty acid esters such as polyethylene glycol monolaurate, polyethylene glycol higher fatty acid esters, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, etc.
- the stabilizer include hydroxypropylmethyl cellulose, polyvinyl alcohol, carboxymethyl cellulose, hydroxyethyl cellulose, glycerin, EDTA and the like.
- buffering agent examples include sodium hydrogenphosphate, potassium hydrogenphosphate, boric acid, sodium borate, citric acid, sodium citrate, tartaric acid, sodium tartrate and the like.
- antioxidant examples include sodium bisulfite, sodium thiosulfite, ascorbic acid and the like.
- antiseptic examples include chlorobutanol, benzalkonium chloride, cetylpyridinium chloride, phenylmercury salt, thimerosal, phenethyl alcohol, methylparaben, propylparaben and the like.
- the eye drop is isotonized with the lacrimal fluid. Therefore, it is preferred to add isotonicities such as sodium chloride, etc., if necessary. It is desirable to adjust the pH of the eye drop within a range of 5.5 to 8.5, preferably 6.5 to 7.5.
- the drug of this invention thus obtained is administered using various administration methods according to the dosage unit form.
- eye drop it is dropped into eyes through a suitable eye dropper or sprayed to eyes through a spraying device.
- ophthalmic ointment it is applied into eyes.
- tablet, granule, etc. it is orally administered.
- injection it is subcutaneously, intramuscularly or intravenously administered.
- the concentration of the carbostyril derivative represented by the formula (1) or a salt thereof in the intraocular irrigating solution is about
- the intraocular irrigating solution can be suitably used for ophthalmic operation, washing, etc.
- the irrigation may be normally conducted once a day.
- Methyl cellulose 0.8 g The above ingredients were mixed using a normal method, and then the resulting mixture was subjected to press molding to produce 1000 tablets.
- lacrimal fluid increasing action test Nictitating membranes of New Zealand White domestic rabbits were excised and animals having no eye abnormality were selected. Tests were initiated after one week. An amount of lacrimal fluid was measured by using a modified primary process of Schirmer's test. That is, the domestic rabbit was fixed to a cylindrical fixing device and, after the animal calmed down, 50 ⁇ l of 0.4 % oxybuprocaine hydrochloride (0.4 % Benoxil, manufactured by Santen Seiyaku Co., Ltd.) was instilled into the right eye.
- 0.4 % oxybuprocaine hydrochloride 0.4 % Benoxil, manufactured by Santen Seiyaku Co., Ltd.
- a drug [8-hydroxy-5-(l-hydroxy-2- isopropylaminobutyl)carbostyril hydrochloride (Procaterol hydrochloride) dissolved into a distilled water at a concentration of 0.001 % by weight] was also instilled into the right eye.
- a piece of Schirmer test paper was inserted into the inferior ophthalmic conjunctiva part.
- the Schirmer test paper was removed to measure the length of the part of the paper wet with tear (for five minutes between 5 and 10 minutes after instillation of the drug).
- a Schirmer test paper was again inserted into the inferior ophthalmic conjunctiva part to measure the amount of lacrimal fluid from 10 to 15 minutes after instillation of the drug.
- New Zealand White domestic rabbits were slaughtered by intravenously administering 250 mg of pentobarbital and their eyeballs were excised. After the tunica conjunctiva bulbi was removed, the cornea and sclera were separated using ophthalmic scissors. The cornea was placed in phosphate buffered saline (PBS) and the Descemet's membrane was removed using tweezers under stereoscopic microscopy.
- PBS phosphate buffered saline
- the cornea sampled from the eyeball was sufficiently washed with PBS and the cells were cultured by the following method to measure the growth acceleration activity of the drug [8-hydroxy-5-(1- hydroxy-2-isopropylaminobutyl )carbostyril hydrochloride (Procaterol hydrochloride)] on the respective cells.
- a piece 2 to 3 mm square of the cornea was made from the cornea using a razor.
- the piece of the cornea was closely placed on a dish for tissue culture and, after a Dulbecco modified Eagle's medium F12 (DME/F-12, 1:1) containing 10 % fetal calf serum (FCS), 10 ng/ml of an epidermal growth factor (EGF) and 10 g/ml of insulin was added, it was cultured at 37 in 5 % CC*2 for two days. After the piece of the cornea was removed, the culturing was conducted for three additional days. The removed piece of the cornea was used for culturing keratocytes.
- DME/F-12 Dulbecco modified Eagle's medium F12
- FCS 10 % fetal calf serum
- EGF epidermal growth factor
- insulin 10 g/ml of insulin
- Keratocytes A piece of the cornea was closely placed on a dish for tissue culture and, after a Dulbecco modified Eagle's medium (DMEM) containing 10 % FCS was added, it was cultured at 37 "C in 5 % CO2 to obtain growth-out keratocytes from the piece of the cornea. (4) Measurement of growth acceleration activity
- the respective cultured cells were subjected to a 0.25 % trypsin-0.01 % EDTA treatment to disengage the cells from the surface of the dish.
- the disengaged cells were suspended in the medium used for culturing the respective cells and, after centrifuging at 1000 rpm for five minutes, the medium was removed under vacuum.
- the cell pellets were again suspended in the medium, and the cell density was adjusted to 4 x 10 4 cells/ml.
- the cells (0.51 ml/well) were then inoculated in a cell culture plate with 24 holes and cultured overnight at 37 "C in 5 % CO2.
- Rabbits (New Zealand White derivation, weight of 2 to 3 kg) were preliminary bred for about one week and slaughtered by intravenously administering pentobarbital. Then, eyeballs were extracted to prepare a corneosclera fragment.
- a carbostyril derivative i.e., 8-hydroxy-5-(1- hydroxy-2-isopropylaminobutyl)carbostyril hydrochloride (Procaterol hydrochloride)] was dissolved in physiological saline at a concentration of 10 " ° M and the irrigating solution thus obtained was subjected to irrigation of the corneal endothelium side to measure the thickness of the cornea using an Ultrasonic Pachymeter.
- ⁇ Thickness means the increased thickness of the cornea.
- the corneal transition of the aqueous humor attended with disorder endothelialis cornea was prevented by adding the carbostyril derivative to an intraocular irrigating solution, which results in inhibition of the increase of the thickness of the cornea attended with corneal edema.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019970700856A KR970704439A (en) | 1994-08-10 | 1995-08-07 | A method of preventing and treating ophthalmic inflammation and / or wound, |
EP95927986A EP0774968A1 (en) | 1994-08-10 | 1995-08-07 | Method of preventing and treating ophthalmic inflammation and/or wound |
MX9701010A MX9701010A (en) | 1994-08-10 | 1995-08-07 | Method of preventing and treating ophthalmic inflammation and/or wound. |
AU31917/95A AU3191795A (en) | 1994-08-10 | 1995-08-07 | Method of preventing and treating ophthalmic inflammation and/or wound |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18830394 | 1994-08-10 | ||
JP6/188303 | 1994-08-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996004911A1 true WO1996004911A1 (en) | 1996-02-22 |
Family
ID=16221257
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1995/001570 WO1996004911A1 (en) | 1994-08-10 | 1995-08-07 | Method of preventing and treating ophthalmic inflammation and/or wound |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0774968A1 (en) |
KR (1) | KR970704439A (en) |
AU (1) | AU3191795A (en) |
CA (1) | CA2197123A1 (en) |
MX (1) | MX9701010A (en) |
WO (1) | WO1996004911A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997013515A1 (en) * | 1995-10-12 | 1997-04-17 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivative for curing ophthalmological diseases |
US6569903B2 (en) | 1999-12-07 | 2003-05-27 | Rohto Pharmaceutical Co., Ltd. | Ophthalmic compositions |
US7879877B2 (en) | 2003-07-30 | 2011-02-01 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives for accelerating salivation |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0020765A1 (en) * | 1978-07-14 | 1981-01-07 | Otsuka Pharmaceutical Co., Ltd. | Medicament against glaucoma |
JPS6452727A (en) * | 1988-05-02 | 1989-02-28 | Santen Pharmaceutical Co Ltd | Antiallergic eye drop |
-
1995
- 1995-08-07 KR KR1019970700856A patent/KR970704439A/en not_active Withdrawn
- 1995-08-07 MX MX9701010A patent/MX9701010A/en unknown
- 1995-08-07 WO PCT/JP1995/001570 patent/WO1996004911A1/en not_active Application Discontinuation
- 1995-08-07 CA CA002197123A patent/CA2197123A1/en not_active Abandoned
- 1995-08-07 EP EP95927986A patent/EP0774968A1/en not_active Withdrawn
- 1995-08-07 AU AU31917/95A patent/AU3191795A/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0020765A1 (en) * | 1978-07-14 | 1981-01-07 | Otsuka Pharmaceutical Co., Ltd. | Medicament against glaucoma |
JPS6452727A (en) * | 1988-05-02 | 1989-02-28 | Santen Pharmaceutical Co Ltd | Antiallergic eye drop |
Non-Patent Citations (5)
Title |
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DATABASE FILE 399: CA SEARCH host: dialog; * |
DATABASE WPI Derwent World Patents Index; AN 89-104873 * |
Y.SAKUMA ET AL.: "Suppression of ocular reactions in cedar pollinosis by procaterol hydrochloride eyedrops", JPN.J.CLIN.OPHTHALMOL., vol. 46, no. 10, October 1992 (1992-10-01), pages 1437 - 1440 * |
Y.SAKUMA, ATARASHII GANKA, vol. 12, no. 3, 1995, pages 466 - 468 * |
Y.YAMAMOTO ET AL.: "Usefulness of Procaterol Eyedrops on Experimental Models of Allergic Conjunctivitis", YAKURI TO CHIRYO, vol. 21, no. 9, September 1993 (1993-09-01), pages 3075 - 3084 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997013515A1 (en) * | 1995-10-12 | 1997-04-17 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivative for curing ophthalmological diseases |
US6060486A (en) * | 1995-10-12 | 2000-05-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivative for curing ophthalmological diseases |
US6569903B2 (en) | 1999-12-07 | 2003-05-27 | Rohto Pharmaceutical Co., Ltd. | Ophthalmic compositions |
US7879877B2 (en) | 2003-07-30 | 2011-02-01 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives for accelerating salivation |
Also Published As
Publication number | Publication date |
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KR970704439A (en) | 1997-09-06 |
AU3191795A (en) | 1996-03-07 |
MX9701010A (en) | 1997-05-31 |
CA2197123A1 (en) | 1996-02-22 |
EP0774968A1 (en) | 1997-05-28 |
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