WO1998047510A1 - Eye drops - Google Patents
Eye drops Download PDFInfo
- Publication number
- WO1998047510A1 WO1998047510A1 PCT/JP1998/001918 JP9801918W WO9847510A1 WO 1998047510 A1 WO1998047510 A1 WO 1998047510A1 JP 9801918 W JP9801918 W JP 9801918W WO 9847510 A1 WO9847510 A1 WO 9847510A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- eye drops
- drugs
- present
- hydrochloride
- vasoconstrictor
- Prior art date
Links
- 239000003889 eye drop Substances 0.000 title claims abstract description 14
- 229940012356 eye drops Drugs 0.000 title claims abstract description 14
- 239000005526 vasoconstrictor agent Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims description 5
- 206010010741 Conjunctivitis Diseases 0.000 abstract description 7
- 208000024891 symptom Diseases 0.000 abstract description 7
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 abstract description 4
- 229960004958 ketotifen Drugs 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 230000000544 hyperemic effect Effects 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 5
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 5
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 5
- 239000002997 ophthalmic solution Substances 0.000 description 5
- 229940054534 ophthalmic solution Drugs 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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 description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 description 4
- 239000000043 antiallergic agent Substances 0.000 description 4
- 229960003630 ketotifen fumarate Drugs 0.000 description 4
- YNQQEYBLVYAWNX-WLHGVMLRSA-N ketotifen fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 YNQQEYBLVYAWNX-WLHGVMLRSA-N 0.000 description 4
- 206010065334 Mucosal hyperaemia Diseases 0.000 description 3
- -1 antibacterial drugs Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 239000000850 decongestant Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 229960005015 local anesthetics Drugs 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- 241000272875 Ardeidae Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 206010010719 Conjunctival haemorrhage Diseases 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- 206010010726 Conjunctival oedema Diseases 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 229960003872 benzethonium Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- FNUZASGZEHGWQM-RJRMRWARSA-M flutropium bromide Chemical compound C[N@+](CCF)([C@H](CC1)C2)[C@@H]1C[C@H]2OC(C(C1=CC=CC=C1)(C1=CC=CC=C1)O)=O.[Br-] FNUZASGZEHGWQM-RJRMRWARSA-M 0.000 description 1
- 229950008319 flutropium bromide Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 229960005162 oxymetazoline hydrochloride Drugs 0.000 description 1
- BEEDODBODQVSIM-UHFFFAOYSA-N oxymetazoline hydrochloride Chemical compound Cl.CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 BEEDODBODQVSIM-UHFFFAOYSA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- KGRJUMGAEQQVFK-UHFFFAOYSA-L platinum(2+);dibromide Chemical compound Br[Pt]Br KGRJUMGAEQQVFK-UHFFFAOYSA-L 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940066263 prednisolone 10 mg Drugs 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 229940000634 serratiopeptidase Drugs 0.000 description 1
- 108010038132 serratiopeptidase Proteins 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- LWRYDHOHXNQTSK-UHFFFAOYSA-N thiophene oxide Chemical compound O=S1C=CC=C1 LWRYDHOHXNQTSK-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- 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
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
Definitions
- the present invention relates to eye drops. Specifically, it is an ophthalmic solution that has an excellent effect of reducing and eliminating congestive symptoms of the ocular mucosa, among other symptoms of conjunctivitis.
- Conjunctivitis is an inflammatory disease of the ocular mucosa, caused by a variety of causes, including bacterial infection, viral infection, allergy, and traumatic disease.
- antibiotics, antibacterial drugs, antiallergic drugs, etc. are administered according to the etiology of the causative therapy.
- symptomatic treatment to reduce and eliminate ocular mucosal hyperemia such as conjunctival congestion, subconjunctival hemorrhage, and conjunctival edema at an early stage is not possible from the viewpoint of Q0L and serious symptoms. It is regarded as a therapeutic point from the viewpoint of preventing migration, and is an important factor especially in drug development.
- vasoconstrictors As such symptomatic treatment, vasoconstrictors, corticosteroids, and the like are currently used, but administration of these drugs alone cannot be said to have obtained sufficient effects from the above viewpoint.
- An object of the present invention is to provide an ophthalmic solution having a high effect on congestion of the ocular mucosa among various symptoms of conjunctivitis. Disclosure of the invention
- the present inventors have conducted intensive studies to achieve the above-mentioned object.
- the inventors have found a dramatic effect on the removal and completed the present invention.
- the present invention does not include a vasoconstrictor and ketotifen or a salt thereof. Eye drops.
- the amount of the vasoconstrictor is 0.0005 to 0.5% by weight, and the amount of the ketothiophene or a salt thereof is 0.05 to 1% by weight based on the total amount of the preparation. Agent.
- vasoconstrictor used in the ophthalmic solution of the present invention examples include naphazolin, tetrahydrozolin, oximetazoline, phenylephrine, efdolins, epinephrine and the like, and salts thereof.
- examples include hydrochloride and nitrate. These can be used alone or in combination of two or more.
- the compounding amount of each active ingredient with respect to the total amount of the ophthalmic preparation of the present invention is preferably 0.0005 to 0.5% by weight, particularly 0.001 to 0.35% by weight for the vasoconstrictor. I like it. If the vasoconstrictor is less than 0.0005% by weight, a sufficient decongestant effect cannot be obtained, and if it exceeds 0.5% by weight, resistance to the action is undesirably produced.
- the content of ketotifen or a salt thereof is preferably from 0.05 to 1% by weight, and particularly preferably from 0.01 to 0.75% by weight.
- the amount of ketotifin or a salt thereof is less than 0.05% by weight, a sufficient antiallergic effect cannot be obtained, and if it exceeds 1% by weight, side effects such as drowsiness and the like on the central nervous system may occur. It is not preferable.
- antiallergic drugs in addition to the above active ingredients, if necessary, other antiallergic drugs, antihistamines, local anesthetics, anticholinergics, steroid antiinflammatory drugs, anti-inflammatory enzyme drugs, anti-inflammatory drugs, Bactericides, vitamins, crude drugs and the like can be added.
- the eye drops of the present invention can be prepared into solid eye drops or liquid eye drops by a conventional method.
- the excipients used in the preparation of pharmaceuticals include excipients such as crystalline cellulose in the case of solid eye drops, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, PVP, and stearyl. There are lubricants such as magnesium phosphate, hardened castor oil and talc, preservatives, etc.
- surfactants, solubilizers, buffers, etc., as well as preservatives, fragrances (menthol, Camphor and the like, pigments, preservatives and the like can be used.
- the eye drops of the present invention are usually administered to an adult by dropping, spraying or applying an appropriate amount once or several times to both eyes at a time.
- Example 2 The above-mentioned components and amounts were weighed and dissolved in purified water (100 m) according to a conventional method to produce. (Example 2)
- Example 3 The above components and amounts were weighed, and dissolved in 100 ml of purified water by a conventional method to produce. (Example 3)
- Example 4 The above components and amounts were weighed and dissolved in 100 ml of purified water by a conventional method to produce. (Example 4)
- the ophthalmic solution of the present invention contains a vasoconstrictor and ketotiphan or a salt thereof, it remarkably reduces and eliminates hyperemia of the ocular mucosa among various symptoms of conjunctivitis.
- the eye drops of the present invention may further contain other antiallergic drugs, antihistamines, local anesthetics, anticholinergics, steroid anti-inflammatory drugs, anti-inflammatory enzyme drugs, anti-inflammatory drugs, bactericides, and vitamins. Since it can be formulated with minerals, crude drugs, etc., it can be used as a prescription drug or a general therapeutic drug as an over-the-counter drug suited to various symptoms of conjunctivitis.
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)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Eye drops containing a vasoconstrictor and ketotifen or its salt. Because of the above composition, the eye drops remarkably relieve, in particular, ophthalmic mucosal congestion among various symptoms of conjunctivitis.
Description
明 細 書 点 眼 剤 技術分野 Description Ophthalmic solution Technical field
本発明は、 点眼剤に関する。 詳しく は、 結膜炎の諸症状のうち特に眼粘膜の充 血症状の軽減除去効果に優れた点眼剤である。 背景技術 The present invention relates to eye drops. Specifically, it is an ophthalmic solution that has an excellent effect of reducing and eliminating congestive symptoms of the ocular mucosa, among other symptoms of conjunctivitis. Background art
結膜炎は眼粘膜の炎症性疾患であり、 その原因は細菌感染によるもの、 ウィル ス感染によるもの、 アレルギーに起因するもの、 外傷性のもの等多岐に亘つてい る。 かかる結膜炎の治療には、 原因療法的にはそれぞれの病因に合わせて、 抗生 物質や抗菌薬、 抗アレルギー薬等の投与が行われる。 しかし、 本疾病にあっては、 結膜充血、 結膜下出血、 結膜浮腫等の眼粘膜の充血症状を早期に軽減除去するた めの対症療法が、 Q 0 Lの観点及び重篤な症状への移行を阻止する観点から治療 上のボイン 卜とされており、 特に医薬品を開発する上においては重要な要素とな る。 Conjunctivitis is an inflammatory disease of the ocular mucosa, caused by a variety of causes, including bacterial infection, viral infection, allergy, and traumatic disease. In the treatment of such conjunctivitis, antibiotics, antibacterial drugs, antiallergic drugs, etc. are administered according to the etiology of the causative therapy. However, in this disease, symptomatic treatment to reduce and eliminate ocular mucosal hyperemia such as conjunctival congestion, subconjunctival hemorrhage, and conjunctival edema at an early stage is not possible from the viewpoint of Q0L and serious symptoms. It is regarded as a therapeutic point from the viewpoint of preventing migration, and is an important factor especially in drug development.
かかる対症療法としては、 現在血管収縮薬、 副腎皮質ホルモン薬等が用いられ ているが、 これらの薬剤の投与のみでは、 上記観点からみて決して充分な効果が 得られているとはいえない。 As such symptomatic treatment, vasoconstrictors, corticosteroids, and the like are currently used, but administration of these drugs alone cannot be said to have obtained sufficient effects from the above viewpoint.
本発明の目的は、 結膜炎の諸症状のうちでも、 特に眼粘膜の充血症状に対する 効果が高い点眼剤を提供することにある。 発明の開示 An object of the present invention is to provide an ophthalmic solution having a high effect on congestion of the ocular mucosa among various symptoms of conjunctivitis. Disclosure of the invention
本発明者らは、 前記目的の達成のために鋭意研究した結果、 点眼剤の有効成分 として血管収縮薬の他にケ 卜チフ ン又はその塩類を配合することにより、 結膜 炎による充血症状の軽減除去に対し劇的な効果があることを見いだし、 本発明を 完成した。 The present inventors have conducted intensive studies to achieve the above-mentioned object. The inventors have found a dramatic effect on the removal and completed the present invention.
すなわち、 本発明は、 血管収縮薬及びケ 卜チフェン又はその塩類を配合してな
る点眼剤である。 That is, the present invention does not include a vasoconstrictor and ketotifen or a salt thereof. Eye drops.
本発明はさらに、 製剤全量に対する配合量が、 前記血管収縮薬は 0 . 0 0 0 5〜 0 . 5重量％、 前記ケ 卜チフヱン又はその塩類は 0 . 0 0 5〜 1重量％である点眼 剤である。 In the present invention, the amount of the vasoconstrictor is 0.0005 to 0.5% by weight, and the amount of the ketothiophene or a salt thereof is 0.05 to 1% by weight based on the total amount of the preparation. Agent.
【発明の実施の形態】 BEST MODE FOR CARRYING OUT THE INVENTION
本発明の点眼剤に用いる血管収縮薬としては、 ナファゾリ ン、 テ卜ラヒ ドロゾ リ ン、 ォキシメ タゾリ ン、 フヱニレフ リ ン、 エフヱ ドリ ン類、 ェピネフ リ ン等及 びこれらの塩類が挙げられ、 前記塩類としては、 塩酸塩、 硝酸塩等が挙げられる。 これらは単独又は 2種以上を組み合わせて用いることができる。 Examples of the vasoconstrictor used in the ophthalmic solution of the present invention include naphazolin, tetrahydrozolin, oximetazoline, phenylephrine, efdolins, epinephrine and the like, and salts thereof. Examples include hydrochloride and nitrate. These can be used alone or in combination of two or more.
本発明の点眼剤の製剤全量に対する各有効成分の配合量は、 血管収縮薬は 0 . 0 0 0 5〜 0 . 5重量％がよく、 0 . 0 0 1 〜 0 . 3 5重量％が特に好ま しい。 血管収 縮薬が 0 . 0 0 0 5重量％未満では、 充分な充血除去効果が得られず、 0 . 5重量 %を超えると作用に対する耐性が生じるので好ま しくない。 また、 ケ トチフェ ン 又はその塩類は 0 . 0 0 5〜 1重量％がよく、 0 . 0 1〜 0 . 7 5重量％が特に好ま しい。 ケ 卜チフヱ ン又はその塩類の配合量が 0 . 0 0 5重量％未満では、 充分な抗 アレルギー効果が得られず、 1重量％を超えると眠気等の中枢神経系の副作用が 生じる場合があるので好ましくない。 The compounding amount of each active ingredient with respect to the total amount of the ophthalmic preparation of the present invention is preferably 0.0005 to 0.5% by weight, particularly 0.001 to 0.35% by weight for the vasoconstrictor. I like it. If the vasoconstrictor is less than 0.0005% by weight, a sufficient decongestant effect cannot be obtained, and if it exceeds 0.5% by weight, resistance to the action is undesirably produced. The content of ketotifen or a salt thereof is preferably from 0.05 to 1% by weight, and particularly preferably from 0.01 to 0.75% by weight. If the amount of ketotifin or a salt thereof is less than 0.05% by weight, a sufficient antiallergic effect cannot be obtained, and if it exceeds 1% by weight, side effects such as drowsiness and the like on the central nervous system may occur. It is not preferable.
本発明においては、 上記有効成分の他、 必要に応じて他の抗アレルギー薬 · 抗 ヒスタ ミ ン薬、 局所麻酔薬、 抗コリ ン薬、 ステロイ ド性抗炎症薬、 消炎酵素薬 · 消炎薬、 殺菌薬、 ビタ ミ ン類、 生薬等を配合することができる。 In the present invention, in addition to the above active ingredients, if necessary, other antiallergic drugs, antihistamines, local anesthetics, anticholinergics, steroid antiinflammatory drugs, anti-inflammatory enzyme drugs, anti-inflammatory drugs, Bactericides, vitamins, crude drugs and the like can be added.
本発明の点眼薬は、 常法により固形状点眼薬又は液状点眼薬に調製することが できる。 製剤の調製に使用する添加剤としては、 固形状点眼薬の場合結晶セル口 —スなどの賦形剤、 ヒ ドロキシプロピルセルロース、 ヒ ドロキシプロピルメチル セルロース、 ゼラチン、 P V Pなどの結合剤、 ステアリ ン酸マグネシウム、 硬化 ヒマシ油、 タルクなどの滑沢剤、 防腐剤等があり、 また液状点眼薬の場合界面活 性剤、 溶解補助剤、 緩衝剤等、 さらに保存剤、 香料 （メ ン トール、 カンフル等） 、 色素、 防腐剤等を使用することができる。 _ The eye drops of the present invention can be prepared into solid eye drops or liquid eye drops by a conventional method. The excipients used in the preparation of pharmaceuticals include excipients such as crystalline cellulose in the case of solid eye drops, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, PVP, and stearyl. There are lubricants such as magnesium phosphate, hardened castor oil and talc, preservatives, etc. In the case of liquid eye drops, surfactants, solubilizers, buffers, etc., as well as preservatives, fragrances (menthol, Camphor and the like, pigments, preservatives and the like can be used. _
本発明の点眼薬は通常、 成人に対して 1回当たり適量を 1回ないし数回両眼に 滴下、 噴霧又は塗布することにより投与する。
発明を実施するための最良の形態 The eye drops of the present invention are usually administered to an adult by dropping, spraying or applying an appropriate amount once or several times to both eyes at a time. BEST MODE FOR CARRYING OUT THE INVENTION
実施例及び試験例を挙げて本発明を更に詳細に説明するが、 下記の例に限定さ れるものではない。 The present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited to the following examples.
(実施例 1 ) (Example 1)
塩酸ナファゾリ ン 3 m g Nafazolin hydrochloride 3 mg
フマル酸ケ トチフェ ン 2 5 m g Ketotifen fumarate 25 mg
グリチルリチン酸ジカリウム 3 0 0 m g Dipotassium glycyrrhizinate 300 mg
塩酸リ ドカイ ン 2 5 0 m g Lidocaine hydrochloride 250 mg
上記の各成分及び分量を秤量し、 常法により精製水 1 0 0 m 】 に溶解し製した。 (実施例 2 ) The above-mentioned components and amounts were weighed and dissolved in purified water (100 m) according to a conventional method to produce. (Example 2)
塩酸テ トラヒ ドロゾリ ン 2 5 m g Tetrahydrodrozolin hydrochloride 25 mg
フマル酸ケ トチフヱン 5 0 m g Ketotifumarate 50 mg
プレ ドニゾロン 1 0 m g Pre-dnisolone 10 mg
塩酸リ ドカイ ン 3 0 0 m g Lidocaine hydrochloride 300 mg
上記の各成分及び分量を秤量し、 常法により精製水 1 0 0 m l に溶解し製した。 (実施例 3 ) The above components and amounts were weighed, and dissolved in 100 ml of purified water by a conventional method to produce. (Example 3)
塩酸テ 卜ラヒ ドロゾリ ン 2 5 m g Tetrahidrozolin hydrochloride 25 mg
フマル酸ケ トチフヱン 3 0 m g Ketotifumarate 30 mg
dl-マレイン酸クロルフエ二ラ ミ ン 2 5 m g dl-Chlorpheniramine maleate 25 mg
プロピオン酸べクロメタゾン l O O m g Beclomethasone propionate l O O m g
塩化リゾチーム 2 5 0 m g Lysozyme chloride 250 mg
塩酸リ ドカイ ン 5 0 0 m g Lidocaine hydrochloride 500 mg
塩化べンゼトニゥム 2 0 m g Benzetonium chloride 20 mg
上記の各成分及び分量を抨量し、 常法により精製水 1 0 0 m l に溶解し製した。 (実施例 4 ) The above components and amounts were weighed and dissolved in 100 ml of purified water by a conventional method to produce. (Example 4)
塩酸ナファゾリ ン 2. 5 m g Nafazolin hydrochloride 2.5 mg
フマル酸ケ トチフェン 2 5 m g Ketotifen fumarate 25 mg
dl-マレイン酸クロルフエ二ラ ミ ン 3 0 m g dl-Chlorpheniramine maleate 30 mg
フルニソリ ド 5 0 m g
臭化フルトロピウム 2 0 m g Flunisolid 50 mg Flutropium bromide 20 mg
セラチオペプチダーゼ 1 0 0 m g Serratiopeptidase 100 mg
塩酸リ ドカイ ン 5 0 0 m g Lidocaine hydrochloride 500 mg
上記の各成分及び分量を秤量し、 常法により精製水 1 0 0 m l に溶解し製した ( (実施例 5 ) Weigh each component and the above amounts of was made by dissolving in purified water 1 0 0 ml in a conventional manner ((Example 5)
塩酸ォキシメタゾリ ン 2 5 m g Oxymetazoline hydrochloride 25 mg
フマル酸ケ 卜チフェン 4 0 m g Ketotifen fumarate 40 mg
テルフェナジン 5 0 m g Terfenadine 50 mg
プロピオン酸フルチカゾン 5 0 m g Fluticasone propionate 50 mg
塩化リゾチーム 2 5 0 m g Lysozyme chloride 250 mg
臭化ィプラ ト口ピウム 2 0 m g Platinum bromide mouth 20 mg
塩酸リ ドカイ ン 5 0 0 m g Lidocaine hydrochloride 500 mg
1 —メ ン トール 1 0 m g 1—Mentor 10 mg
上記の各成分及び分量を秤量し、 常法により精製水 1 0 0 m l に溶解し製した。 (試験例） [配合製剤のゥサギ眼粘膜充血反応に対する緩解作用] The above components and amounts were weighed, and dissolved in 100 ml of purified water by a conventional method to produce. (Test example) [Relief action of the combined preparation on the hyperglycemic reaction of ophthalmic mucosa of the egret]
〈試験方法〉 <Test method>
各群 3匹のゥサギを用いあらかじめ 3 . 5 %カブサイシン液 1 m 1 を点眼して眼 粘膜の充血反応を惹起し、 表 1の処方 （ 1 0 0 m 1 中） に従い、 それぞれ 1 m 1 の薬剤を点眼して点眼後 1時間の時点における充血除去効果を比較した。 Inoculation of 3.5% cabsaicin solution (1 ml) was performed in advance using 3 rabbits in each group to induce hyperemia of the ocular mucosa, and 1 ml of 1 ml each was used according to the prescription in Table 1 (in 100 ml). The drug was instilled, and the decongestant effect at 1 hour after instillation was compared.
評価法としては、 5点 ； 非常に充血している、 4点； かなり充血している、 3 点 ； はっきり充血している、 2点 ； やや充血している、 1点 ； 充血しているが非 常に弱い、 0点 ； ほとんど充血していない、 の 6段階評価で行い、 3匹間の平均 値で比較した。
群 A群 B群 C群 D群 E群 成分 (%) (%) (%) (%) (%) 塩酸フエ二レフリン 0. 1 0. 0 5 0. 1 0. 0 5 / フマル酸ケトチフェン 0. 0 5 0. 0 5 / / 0. 0 5 マレイン酸クロルフエ二ラミン / / / / / As the evaluation method, 5 points; very hyperemic, 4 points; considerably hyperemic, 3 points; clearly hyperemic, 2 points; slightly hyperemic, 1 point; hyperemic Very weak, 0 points; almost no congestion, and a 6-point scale was used. Group A Group B Group C Group D Group E Ingredients (%) (%) (%) (%) (%) Furefrefline hydrochloride 0.1 1 0. 0 5 0. 1 0. 0 5 0. 0 5 / / 0. 0 5 Chlorpheniramine maleate / / / / /
群 F群 G群 H群 I群 成分 (%) (%) (%) (%) 塩酸フエニレ7リン 0. 1 0. 0 5 / / Group F Group G Group H Group I Ingredients (%) (%) (%) (%) Phenyle 7 hydrochloride 0.1 1 0.
フマル酸ケトチフェン / / / / Ketotifen fumarate / / / /
マレイン酸クロルフエ二ラミン 0. 0 5 0. 0 5 0. 0 5 / Chlorpheniramine maleate 0.05 0.0 5 0.05 /
〈試験結果〉 <Test results>
結果を充血反応の程度評点として表 2に示す c C shown in Table 2 results as the degree scores hyperemic reactions
表 2 Table 2
表 2から明らかなように、 眼粘膜充血反応に対する緩解作用は、 A及び B群が 他の群より著しく優っており、 本発明の点眼薬が、 血管収縮薬及びフマル酸ケ 卜 チフヱンを単独で使用した場合、 ならびに血管収縮薬と他の抗ァレルギ一薬を組
み合わせた場合と比較して、 眼粘膜充血症状の軽減除去作用において顕著な効果 を有することがわかる。 業上の利用可能件 As is evident from Table 2, the remission effect on ocular mucosal hyperemia was markedly superior in the A and B groups compared to the other groups. If used, and in combination with vasoconstrictors and other anti-allergic drugs It can be seen that it has a remarkable effect on the action of reducing and eliminating ocular mucosal hyperemia as compared to the combined case. Business availability
本発明の点眼剤は、 血管収縮薬及びケ トチフヱン又はその塩類を配合してなる ので、 結膜炎の諸症状のうちでも特に眼粘膜の充血症状を著しく軽減除去する。 また、 本発明の点眼剤は、 さらに他の抗アレルギー薬、 抗ヒスタ ミ ン薬、 局所 麻酔薬、 抗コリ ン薬、 ステロイ ド性抗炎症薬、 消炎酵素薬 · 消炎薬、 殺菌薬、 ビ タ ミ ン類、 生薬等を配合することができるので、 結膜炎の諸症状に合わせた処方 薬や一般用医薬品としての総合治療薬とすることができる。
Since the ophthalmic solution of the present invention contains a vasoconstrictor and ketotiphan or a salt thereof, it remarkably reduces and eliminates hyperemia of the ocular mucosa among various symptoms of conjunctivitis. Further, the eye drops of the present invention may further contain other antiallergic drugs, antihistamines, local anesthetics, anticholinergics, steroid anti-inflammatory drugs, anti-inflammatory enzyme drugs, anti-inflammatory drugs, bactericides, and vitamins. Since it can be formulated with minerals, crude drugs, etc., it can be used as a prescription drug or a general therapeutic drug as an over-the-counter drug suited to various symptoms of conjunctivitis.
Claims
1. 血管収縮薬及びケ 卜チフエ ン又はその塩類を配合してなる点眼剤。 1. Eye drops containing a vasoconstrictor and ketothiphene or a salt thereof.
2. 製剤全量に対する配合量が、 血管収縮薬は 0. 0 0 0 5〜 0. 5重量％、 ケ トチフヱン又はその塩類は 0. 0 0 5〜 1重量％である請求の範囲第 1項記載の点 眼剤。
2. Claim 1 wherein the amount of the vasoconstrictor is 0.005 to 0.5% by weight, and the content of ketotiphan or its salts is 0.005 to 1% by weight based on the total amount of the preparation. Eye drops.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU70815/98A AU7081598A (en) | 1997-04-24 | 1998-04-24 | Eye drops |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9/107850 | 1997-04-24 | ||
| JP10785097 | 1997-04-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998047510A1 true WO1998047510A1 (en) | 1998-10-29 |
Family
ID=14469654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1998/001918 WO1998047510A1 (en) | 1997-04-24 | 1998-04-24 | Eye drops |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU7081598A (en) |
| WO (1) | WO1998047510A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008026756A1 (en) * | 2006-08-28 | 2008-03-06 | Senju Pharmaceutical Co., Ltd. | Ophthalmic percutaneous absorption type preparation |
| EP3653205A3 (en) * | 2011-03-03 | 2020-08-26 | Voom, LLC | Oxymethazoline for topical ophthalmic administration and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62277323A (en) * | 1986-02-19 | 1987-12-02 | Sankyo Co Ltd | Production of eye drop containing ketotifen fumarate |
| JPH03128332A (en) * | 1989-07-12 | 1991-05-31 | Eisai Co Ltd | Alpha1-blocker eye drop lotion |
-
1998
- 1998-04-24 AU AU70815/98A patent/AU7081598A/en not_active Abandoned
- 1998-04-24 WO PCT/JP1998/001918 patent/WO1998047510A1/en active Search and Examination
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62277323A (en) * | 1986-02-19 | 1987-12-02 | Sankyo Co Ltd | Production of eye drop containing ketotifen fumarate |
| JPH03128332A (en) * | 1989-07-12 | 1991-05-31 | Eisai Co Ltd | Alpha1-blocker eye drop lotion |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008026756A1 (en) * | 2006-08-28 | 2008-03-06 | Senju Pharmaceutical Co., Ltd. | Ophthalmic percutaneous absorption type preparation |
| EP3653205A3 (en) * | 2011-03-03 | 2020-08-26 | Voom, LLC | Oxymethazoline for topical ophthalmic administration and uses thereof |
| US10912765B2 (en) | 2011-03-03 | 2021-02-09 | Voom, Llc | Compositions and methods for non-surgical treatment of ptosis |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7081598A (en) | 1998-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI620569B (en) | Non-irritating ophthalmic povidone-iodine compositions | |
| JP3402613B2 (en) | Eye drops | |
| JPS61500225A (en) | eye drop composition | |
| JP2002501884A (en) | Nasal solution | |
| EP1928444A2 (en) | Use of ambroxol for the treatment of rhinovirus infections | |
| JP5132015B2 (en) | Eye drop composition | |
| JP4457422B2 (en) | Nasal composition | |
| JPH11189533A (en) | Eye drop | |
| JP3527256B2 (en) | Antiallergic eye drops | |
| WO2001087304A1 (en) | Ophthalmic solution | |
| WO2003035109A1 (en) | Remedies for pruritus | |
| WO1998047510A1 (en) | Eye drops | |
| JP2002308764A (en) | Pharmaceutical composition for ophthalmic use | |
| JP2002161032A (en) | Composition applied to mucous membrane | |
| JP2013049729A (en) | Pharmaceutical composition | |
| JPH115750A (en) | Ophthalmic solution | |
| JP3987501B2 (en) | Pharmaceutical composition | |
| JPH11147825A (en) | Improvement of absorption from mucous membrane and preparation for external use for mucous membrane | |
| JP2005008596A (en) | Ophthalmological composition | |
| JPH05286860A (en) | Gel ointment | |
| JP2002020284A (en) | Eye lotion | |
| JPH0967256A (en) | Drug for common cold | |
| JP2004143154A (en) | Ophthalmic solution | |
| JPH10330257A (en) | Inhibitor of cytokine production for ocular topical use | |
| JPH0262821A (en) | Anticatalactous agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA CN KR US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |
|
| DPE2 | Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101) |