NL7920004A - COMPOSITIONS FOR TREATING GREEN CATHARAS. - Google Patents
COMPOSITIONS FOR TREATING GREEN CATHARAS. Download PDFInfo
- Publication number
- NL7920004A NL7920004A NL7920004A NL7920004A NL7920004A NL 7920004 A NL7920004 A NL 7920004A NL 7920004 A NL7920004 A NL 7920004A NL 7920004 A NL7920004 A NL 7920004A NL 7920004 A NL7920004 A NL 7920004A
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- Prior art keywords
- compositions
- green
- hydroxy
- formula
- ophthalmic
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims description 28
- 208000002177 Cataract Diseases 0.000 claims description 15
- -1 carbostyril compound Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N carbostyril Natural products C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 10
- 239000002997 ophthalmic solution Substances 0.000 description 10
- 239000000969 carrier Substances 0.000 description 6
- 230000004410 intraocular pressure Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000003885 eye ointment Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 229960000686 benzalkonium chloride Drugs 0.000 description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 229940054534 ophthalmic solution Drugs 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GHQFLMULNSGOAR-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;sodium Chemical compound [Na].OC(=O)C(O)C(O)C(O)=O GHQFLMULNSGOAR-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000003123 bronchiole Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- MUHFRORXWCGZGE-KTKRTIGZSA-N 2-hydroxyethyl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCO MUHFRORXWCGZGE-KTKRTIGZSA-N 0.000 description 1
- QVKSJODVQXGNCG-UHFFFAOYSA-N 8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC QVKSJODVQXGNCG-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- AEQDBKHAAWUCMT-UHFFFAOYSA-N Procaterol hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC AEQDBKHAAWUCMT-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- LNGNZSMIUVQZOX-UHFFFAOYSA-L disodium;dioxido(sulfanylidene)-$l^{4}-sulfane Chemical compound [Na+].[Na+].[O-]S([O-])=S LNGNZSMIUVQZOX-UHFFFAOYSA-L 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 150000002730 mercury Chemical class 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
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 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
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 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
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 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
- 230000004304 visual acuity Effects 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Quinoline Compounds (AREA)
Description
794002/vdV/vdKl/hh794002 / vdV / vdKl / hh
Korte aanduiding : Samenstellingen voor het behandelen van groene staar*Short designation: Green cataract treatment compositions *
De uitvinding heeft betrekking op samenstellingen voor het behandelen van groene staar.The invention relates to compositions for treating green cataracts.
Groene staar wordt voornamelijk toegeschreven aan een voortdurende of herhaalde toename van de intra-oculaire druk en leidt 5 tot functionele en verdere organische afwijkingen van het oog. Voor de behandeling van deze ziekte wordt het verminderen van de toename van de intra-oculaire druk tot het normale niveau om de juiste gezichtsscherpte te handhaven bijzonder belangrijk geacht (Masakichi Mikuni en Kazuo Iwata, "Glaucoma," Kanehara Shuppan Co.,Ltd., 1968). 10 De samenstellingen volgens de uitvinding voor de behandeling van groene staar bevatten als werkzaam bestanddeel een carbostyril verbinding met formule 1 van het formuleblad, waarin R^ en R^ elk een lagere alkylgroep voorstellen en de koolstof-koolstofbinding tussen plaats 3 en 4 van de carbostyrilketen een enkele of een 15 dubbele binding is, of een zuur addiiiezout hiervan.Green cataract is mainly attributed to a continuous or repeated increase in intraocular pressure and leads to functional and further organic abnormalities of the eye. For the treatment of this disease, reducing the increase in intraocular pressure to normal levels to maintain proper visual acuity is considered particularly important (Masakichi Mikuni and Kazuo Iwata, "Glaucoma," Kanehara Shuppan Co., Ltd., 1968). The compositions of the invention for the treatment of green cataract contain as active ingredient a carbostyril compound of formula 1 of the formula sheet, wherein R 1 and R 1 each represent a lower alkyl group and the carbon-carbon bond between positions 3 and 4 of the carbostyril chain is a single or a double bond, or an acid addition salt thereof.
De lagere alkylgroepen die in formule 1 zijn weergegeven met R^ en R£ zijn onvertakte of vertakte alkylgroepen met 1 tot 4 koolstofatomen, zoals methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, enz. Bruikbare zuuradditiezouten van de carbostyrilver-20 bindingen met formule 1 zijn zuuraditiezouten die gewoonlijk farmaceutisch aanvaardbaar zijn en omvatten bijvoorbeeld de zouten van zoutzuur, zwavelzuur, salpeterzuur, broomwaterstofzuur, oxaalzuur, maleïnezuur, fumaarzuur, citroenzuur, wijnsteenzuur, enz.The lower alkyl groups represented by R 1 and R 2 in Formula 1 are straight or branched chain alkyl groups of 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, etc. Useful acid addition salts of the carbostyrilver-20 compounds of formula 1 are acid addition salts which are usually pharmaceutically acceptable and include, for example, the salts of hydrochloric, sulfuric, nitric, hydrobromic, oxalic, maleic, fumaric, citric, tartaric, etc.
Kenmerkende voorbeelden van de werkzame verbindingen met 25 formule 1 die kunnen worden toegepast in de samenstellingen voor het behandelen van groene staar volgens de uitvinding zijn: 8-Hydroxy-5-(l-hydroxy-2-isopropylaminobutyl)carbostyril 8-Hydroxy-5-(l-hydroxy-2-tert-butylaminopropyl)carbostyril 8-Hydroxy-5-(l*hydroxy-2-ethylaminobutyl)-3,4-dihydrocarbostyril 30 8-Hydroxy-5-(l-hydroxy-2-isopropylaminobutyl)3,4-dihydrocarbostyril 7920004 -2-Typical examples of the active compounds of formula 1 which can be used in the green cataract treatment compositions of the invention are: 8-Hydroxy-5- (1-hydroxy-2-isopropylaminobutyl) carbostyril 8-Hydroxy-5- (1-hydroxy-2-tert-butylaminopropyl) carbostyril 8-Hydroxy-5- (1 * hydroxy-2-ethylaminobutyl) -3,4-dihydrocarbostyril 30 8-Hydroxy-5- (1-hydroxy-2-isopropylaminobutyl) 3 , 4-dihydrocarbostyril 7920004 -2-
De verbindingen met formule 1 die als werkzame bestanddelen kunnen worden toegepast zijn bekende verbindingen die bijvoorbeeld worden bereid volgens de in de Japanse octrooiaanvrage 10994/1978 beschreven wijze. De werkzame verbindingen bezitten bronchodilata-5 tiewerking en kunnen worden toegepast voor het genezen van brochia-le asthma.The compounds of formula 1 which can be used as active ingredients are known compounds which are prepared, for example, in the manner described in Japanese patent application 10994/1978. The active compounds have bronchodilator activity and can be used to cure brochial asthma.
De uitvinding is gebaseerd op het feit dat een groepwoarbo-styrilverbindingen, die bekende middelen vormen voor het behandelen van bronchiole asthma, verbindingen omvatten die een werkzaamheid 10 bezitten als middelen voor de behandeling van groene staar, namelijk een vermindering van de intra-oculaire druk, die niet was te verwachten op grond van de werking als middel voor de behandeling van bronchiole asthma.The invention is based on the fact that a group of woarbo-styril compounds, which are known agents for treating bronchiole asthma, comprise compounds which have an activity as agents for the treatment of green cataracts, namely a reduction of the intraocular pressure, not expected due to its activity as a treatment for bronchiole asthma.
De samenstellingen voor het behandelen van groene staar 15 volgens de uitvinding kunnen in een geschikte toedieningsvorm gebracht worden door een verbinding met formule 1 of een zuuradditie-zout hiervan met een voor afthalmische preparaten geschikte drager te mengen. De samenstellingen kunnen elke gebruikelijke toedieningsvorm bezitten, zoals ofthalmiscbe zalven, ofthalmische oplossingen, 20 enz. voor plaatselijke toediening, en tabletten, korrels en injec-tieoplossingen, enz. voor algemene toediening. Het verdient in het bijzonder de voorkeur de samenstellingen volgens de uitvinding toe te passen als ofthalmische oplossingen.The compositions for treating green cataracts of the invention can be brought into a suitable dosage form by mixing a compound of formula 1 or an acid addition salt thereof with a carrier suitable for ophthalmic preparations. The compositions may be in any conventional administration form, such as ophthalmic ointments, ophthalmic solutions, etc., for topical administration, and tablets, granules and injection solutions, etc., for general administration. It is particularly preferred to use the compositions of the invention as ophthalmic solutions.
Hoewel de dosering van de onderhavige samenstellingen niet 25 bijzonder beperkt is, worden de samenstellingen gewoonlijk toegediend in een dagelijkse dosis van 0,01 tot 0,5 mg, bij voorkeur 0,05 tot 0,1 mg. voor een volwassene, berekend als het werkzame bestanddeel van de samenstellingen. Bij voorkeur worden de samenstellingen toegediend in in twee tot drie hoeveelheden verdeelde 30 dagelijkse doses. Gewoonlijk verdient het de voorkeur dat de hoeveelheid werkzaam bestanddeel in de samenstellingen ongeveer 7920004 -3- 0,04 tot ongeveer 2 gew./2 bedraagt.Although the dosage of the present compositions is not particularly limited, the compositions are usually administered in a daily dose of 0.01 to 0.5 mg, preferably 0.05 to 0.1 mg. for an adult, calculated as the active ingredient of the compositions. Preferably, the compositions are administered in two to three divided doses daily. Usually, it is preferred that the amount of active ingredient in the compositions is from about 7920004-3.04 to about 2% w / w.
De samenstellingen volgens de uitvinding kunnen op bekende wijze worden bereid onder toepassing van de verbinding met formule 1 of een zuuradditiezout hiervan als werkzaam bestanddeel, doordat 5 men een geschikte drager of excipiens mengt, en het mengsel desgewenst in de gewenste toedieningsvorm brengt. De samenstellingen worden wanneer zij in de vorm van ofthalmische zalven ofthalmische oplossingen of injectieoplossingen zijn gebracht, vervolgens geste-10 riliseerd. Geschikte dragers of verdunningsmiddelen worden gekozen in overeenstemming met de vorm van de samenstellingen. Voorbeelden van voor de bereiding van ofthalmische zalven bruikbare dragers zijn: emulgeerbare dragers, wateroplosbare dragers en suspendeerbare dragers. Voorbeelden van dergelijke dragers zijn witte vaseline, gezui-15 verde lanoline, vloeibare paraffine, enz. Een voorbeeld van een verdunningsmiddel voor de bereiding van ofthalmische oplossingen is gesteriliseerd gedestilleerd water.The compositions of the invention can be prepared in known manner using the compound of formula 1 or an acid addition salt thereof as the active ingredient by mixing a suitable carrier or excipient and bringing the mixture into the desired dosage form, if desired. The compositions, when placed in the form of ophthalmic ointments, ophthalmic solutions or injection solutions, are then sterilized. Suitable carriers or diluents are selected in accordance with the form of the compositions. Examples of carriers useful for the preparation of ophthalmic ointments are: emulsifiable carriers, water-soluble carriers and suspensible carriers. Examples of such carriers are white petrolatum, purified lanolin, liquid paraffin, etc. An example of a diluent for the preparation of ophthalmic solutions is sterilized distilled water.
Solubiliserende middelen, stabilisatoren, buffers, anti-oxydantia, conserveringsmiddelen, enz. kunnen eveneens aan de samen-20 stellingen volgens de uitvinding worden toegevoegd. Voorbeelden van bruikbare solubiliserende middelen zijn natriumcarboxymethylcellulose; polyoxythyleenethers zoals polyoxyethyleenlaurylether en polyoxyethy-leenoleylether; hogere vetzuuresters van polyethyleenglycol zoals polyethyleenglycolmonooleaat en polyethyleenglycolmonolauraat ; 25 vetzuuresters van polyoxyethyleen zoals polyoxyethyleensorbitanmono-lauraat en polyoxyethyleensorbitanmonoleaat; enz. Voorbeelden van bruikbare stabilisatoren zijn hydroxypropylmethylcellulose, polyvinyl-alcohol, carboxymethylcellulose, hydroxyethylcellulose, glycerol, EDTA, enz. Voorbeelden van bruikbare buffers zijn natriumbifosfaat, 30 kaliumbifosfaat, boorzuur, natriumboraat, citroenzuur, natriumcitraat, wijnsteenzuur, natriumtartraat, enz. Voorbeelden van bruikbare anti-oxydantia zijn natriumbisulfiet, natriumthiosulfiet, ascorbinezuur, enz. Voorbeelden van bruikbare conserveringsmiddelen zijn chloorbuta- 7920004 -4- nol, benzalkoniumchloride, cet^ylpyridiniumchloride, phynylkwikzout, thimerosdl, phenetylalcohol, methylparaben, propylparaben enz.Solubilizers, stabilizers, buffers, antioxidants, preservatives, etc. can also be added to the compositions of the invention. Examples of useful solubilizing agents are sodium carboxymethyl cellulose; polyoxyethylene ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether; higher fatty acid esters of polyethylene glycol such as polyethylene glycol monooleate and polyethylene glycol monolaurate; Fatty acid esters of polyoxyethylene such as polyoxyethylene sorbitan monolaurate and polyoxyethylene sorbitan monoleate; etc. Examples of useful stabilizers are hydroxypropylmethylcellulose, polyvinyl alcohol, carboxymethylcellulose, hydroxyethylcellulose, glycerol, EDTA, etc. Examples of useful buffers are sodium biphosphate, potassium biphosphate, boric acid, sodium borate, citric acid, sodium citrate, tartaric acid, sodium tartaric acid, examples of sodium tartaric acid. anti-oxidants are sodium bisulfite, sodium thiosulfite, ascorbic acid, etc. Examples of useful preservatives are chlorobutan 7920004 -4-nol, benzalkonium chloride, cetyl pyridinium chloride, phynyl mercury salt, thimerosdl, phenethyl alcohol, methyl paraben, propyl paraben, etc.
De samenstellingen volgens de uitvinding dienen, wanneer 5 zij ofthalmische oplossingen zijn, bij voorkeur isotonisch te worden gemaakt met tranen. Hiervoor kan gewoon zout of een dergelijke verbinding naar wens aan de samenstellingen worden toegevoegd. Het is gewenst de pH van de ofthalmische oplossingen op 5,5 tot 8,5 , bij voorkeru 6,5 tot 7,5 , te brengen.The compositions of the invention, when they are ophthalmic solutions, should preferably be made isotonic with tears. For this, ordinary salt or the like compound can be added to the compositions as desired. It is desirable to adjust the pH of the ophthalmic solutions to 5.5 to 8.5, preferably 6.5 to 7.5.
10 De aldus bereide samenstellingen volgens de uitvinding voor de behandeling van groene staar worden op verschillende wijzen aan patiënten gegeven, in overeenstemming met de vorm van de preparaten. Ofthalmische oplossingen worden druppelsgewijze uit een geschikte houder op het oog gebracht of op het oog verstoven met een verstuiver.The compositions of the invention thus prepared for the treatment of green cataracts are given to patients in various ways, according to the form of the preparations. Ophthalmic solutions are applied dropwise from a suitable container to the eye or sprayed onto the eye with a nebulizer.
15 Ofthalmische zalven worden eveneens op het oog gebracht. Tabletten en korrels worden oraal toegediend, terwijl injektieoplossingen sub-cutaan,intramusculair of intraveneus worften toe gediend. De gewenste genezende werking kan in elk van deze gevallen worden verkregen.15 Ophthalmic ointments are also applied to the eye. Tablets and granules are administered orally, while injection solutions are administered subcutaneously, intramuscularly or intravenously. The desired healing effect can be obtained in either of these cases.
De uitvinding zal nader worden toegelicht aan de hand van 20 niet-beperkende bereidingsvoorbeelden en het onderzoek naar de medicinale werking.The invention will be further elucidated by means of non-limiting preparation examples and research into the medicinal effect.
Voorbeeld I.Example I.
8-Hydroxy-5-(l-hydroxy-2-isopropylaminobutyl)- carbostyrilhydrochloride 0,2 .g 25 Benzalkoniumchloride 0,01 g8-Hydroxy-5- (1-hydroxy-2-isopropylaminobutyl) carbostyril hydrochloride 0.2 g Benzalkonium chloride 0.01 g
Natriumdiwaterstoffosfaat 0,56 gSodium dihydrogen phosphate 0.56 g
Kaliumdiwaterstoffosfaat 0,8 gPotassium dihydrogen phosphate 0.8 g
Gedestilleerd water_geschikte hoeveelheidDistilled water_suitable amount
Totaal 100 ml 30 De bestanddelen lost men op in gedestilleerd water, en men steriliseert de oplossing door deze met een geschikt filtreerpapier te filtreren om een samenstelling voor het behandelen van groene 7920004 -5- staar in de vorm van een ofthalmische oplossing te verkrijgen. Voorbeeld II.Total 100 ml. The ingredients are dissolved in distilled water, and the solution is sterilized by filtering it with a suitable filter paper to obtain a composition for treating green 7920004 -5 cataract in the form of an ophthalmic solution. Example II.
8-Hydroxy-5-(l-hydroxy-2-isopropylaminobutyl- 3,4-dihydrocarbostyril hydrochloride 0,2 g 5 Benzalkoniumchloride 0,01 g8-Hydroxy-5- (1-hydroxy-2-isopropylaminobutyl-3,4-dihydrocarbostyril hydrochloride 0.2 g 5 Benzalkonium chloride 0.01 g
Natriumdiwaterstoffosfaat 0,56 gSodium dihydrogen phosphate 0.56 g
Kaliumdiwaterstoffosfaat 0,8 gPotassium dihydrogen phosphate 0.8 g
Gedestilleerd water_geschikte hoeveelheidDistilled water_suitable amount
Totaal 100 ml 10 Men lost de bestanddelen op in gedestilleerd water, en steriliseert de oplossing door filtreren met een geschikt filtreer-papier om een samenstelling voor de behandeling van groene staar volgens de uitvinding in de vorm van een ofthalmische oplossing te 15 verkrijgen.Total 100 ml. The ingredients are dissolved in distilled water, and the solution is sterilized by filtration with a suitable filter paper to obtain a green cataract treatment composition according to the invention in the form of an ophthalmic solution.
Werkzaamheidsproef.Efficacy test.
Men brengt een druppel (ongeveer 25 μΐ) van de ofthalmische die oplossing/volgens voorbeeld I is verkregen, twee maal per dag, 's morgens en 's avonds, gedurende drie dagen op beide ogen van drie 20 mannelijke patiënten met open hoek-groene staar.One drop (about 25 μΐ) of the ophthalmic solution obtained according to Example I is applied twice a day, morning and evening, for three days on both eyes of three 20 male patients with open angle green cataracts.
De intra-oculaire druk van het oog meet men tussen 10 uur en 11 uur 's avonds met behulp van een Goldmann applanatie tonometer. In tabel A zijn de resultaten weergegeven.The intraocular pressure of the eye is measured between 10 a.m. and 11 p.m. using a Goldmann applanation tonometer. The results are shown in Table A.
792 00 0 4792 00 0 4
-6-TABEL A-6-TABLE A
Intro-oculaire druk (mm Hg)Introocular pressure (mm Hg)
Patient Voor na 1 dag na 2 dagen na 3 dagen toediening 5 1 L.O.* 3ÏT64 2ÏT35 Ϊ3Γ46 ΊΟδ A --TT------ R.O. * 25.32 17.42 14.75 15.67 UO 38.85 23.78 24.52 21.27 B ------ R.O. 35.43 21.47 23.38 20.69 L.O. 23.57 18.68 14.75 16.37 C ------ 10 R.O. 26.17 17.95 15.74 14.65Patient Before after 1 day after 2 days after 3 days of administration 5 1 L.O. * 3ÏT64 2ÏT35 Ϊ3Γ46 ΊΟδ A --TT ------ R.O. * 25.32 17.42 14.75 15.67 UO 38.85 23.78 24.52 21.27 B ------ R.O. 35.43 21.47 23.38 20.69 L.O. 23.57 18.68 14.75 16.37 C ------ 10 R.O. 26.17 17.95 15.74 14.65
Linker oog ** Rechter oogLeft eye ** Right eye
Tabel A toont dat de samenstelling volgens de uitvinding voor de behandeling van groene staar de intra-oculaire druk bij de 15 patiënten met groene staar sterk vermindert en een uitstekende therapeutische werking verschaft.Table A shows that the composition according to the invention for the treatment of green cataracts greatly reduces the intraocular pressure in the 15 patients with green cataracts and provides an excellent therapeutic effect.
De groene staar behandelende samenstelling, verkregen in Voorbeeld II, is op dezelfde wijze onderzocht op de werkzaamheid. De samenstelling verschaft vrijwel dezelfde vermindering van de intra-20 oculaire druk.The green cataract-treating composition obtained in Example II has been similarly tested for efficacy. The composition provides much the same reduction in intra-20 ocular pressure.
79200047920004
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8623178 | 1978-07-14 | ||
| JP8623178A JPS5513241A (en) | 1978-07-14 | 1978-07-14 | Remedy for glaucoma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL7920004A true NL7920004A (en) | 1980-05-30 |
Family
ID=13881010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL7920004A NL7920004A (en) | 1978-07-14 | 1979-07-13 | COMPOSITIONS FOR TREATING GREEN CATHARAS. |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0020765A1 (en) |
| JP (1) | JPS5513241A (en) |
| CH (1) | CH643143A5 (en) |
| DE (1) | DE2952959C2 (en) |
| GB (1) | GB2039739B (en) |
| NL (1) | NL7920004A (en) |
| SE (1) | SE451070B (en) |
| WO (1) | WO1980000215A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU518814B2 (en) * | 1979-01-30 | 1981-10-22 | Otsuka Pharamaceutical Co. | Glaucoma treatment |
| JPS57172004A (en) * | 1981-04-17 | 1982-10-22 | Nichireki Chem Ind Co | Construction of bitminous thin layered pavement |
| FR2539413A1 (en) * | 1983-01-17 | 1984-07-20 | Pos Lab | CARBOSTYRILOXIMINOPROPANOLAMINES USEFUL AS MEDICAMENTS AND PROCESS FOR THEIR PREPARATION |
| JPH0726362B2 (en) * | 1985-04-08 | 1995-03-22 | 日瀝化学工業株式会社 | Bituminous pavement construction method |
| KR970704439A (en) * | 1994-08-10 | 1997-09-06 | 오쓰카 아키히코 | A method of preventing and treating ophthalmic inflammation and / or wound, |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5310994B2 (en) * | 1974-06-13 | 1978-04-18 | ||
| US4022776A (en) * | 1974-01-31 | 1977-05-10 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]ethyl-8-hydroxycarbostyril derivatives |
| DK230476A (en) * | 1976-05-26 | 1977-11-27 | E H Sahlertz | LIGHT SIGNS AND WRITING EQUIPMENT |
-
1978
- 1978-07-14 JP JP8623178A patent/JPS5513241A/en active Granted
-
1979
- 1979-07-13 NL NL7920004A patent/NL7920004A/en unknown
- 1979-07-13 GB GB8007253A patent/GB2039739B/en not_active Expired
- 1979-07-13 WO PCT/JP1979/000185 patent/WO1980000215A1/en not_active Ceased
- 1979-07-13 CH CH205680A patent/CH643143A5/en not_active IP Right Cessation
- 1979-07-13 DE DE19792952959 patent/DE2952959C2/en not_active Expired
-
1980
- 1980-02-25 EP EP79900778A patent/EP0020765A1/en not_active Ceased
- 1980-03-13 SE SE8001981A patent/SE451070B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GB2039739B (en) | 1983-01-26 |
| SE451070B (en) | 1987-08-31 |
| DE2952959C2 (en) | 1986-08-28 |
| EP0020765A4 (en) | 1980-12-02 |
| CH643143A5 (en) | 1984-05-30 |
| EP0020765A1 (en) | 1981-01-07 |
| GB2039739A (en) | 1980-08-20 |
| JPS611007B2 (en) | 1986-01-13 |
| WO1980000215A1 (en) | 1980-02-21 |
| JPS5513241A (en) | 1980-01-30 |
| DE2952959T1 (en) | 1981-01-08 |
| SE8001981L (en) | 1980-03-13 |
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