DE2330338A1 - Okular-hypotensives mittel - Google Patents
Okular-hypotensives mittelInfo
- Publication number
- DE2330338A1 DE2330338A1 DE2330338A DE2330338A DE2330338A1 DE 2330338 A1 DE2330338 A1 DE 2330338A1 DE 2330338 A DE2330338 A DE 2330338A DE 2330338 A DE2330338 A DE 2330338A DE 2330338 A1 DE2330338 A1 DE 2330338A1
- Authority
- DE
- Germany
- Prior art keywords
- isoproterenol
- salt
- ophthalmologically
- intraocular pressure
- agent according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002220 antihypertensive agent Substances 0.000 title description 2
- 230000004410 intraocular pressure Effects 0.000 claims description 28
- JWZZKOKVBUJMES-LLVKDONJSA-N 4-[(1S)-1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol Chemical compound CC(C)NC[C@@H](O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-LLVKDONJSA-N 0.000 claims description 25
- 230000000694 effects Effects 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 229940039009 isoproterenol Drugs 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- LBOPECYONBDFEM-VUAFVNRWSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;4-[(1s)-1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol Chemical group OC(=O)[C@H](O)[C@@H](O)C(O)=O.CC(C)NC[C@@H](O)C1=CC=C(O)C(O)=C1 LBOPECYONBDFEM-VUAFVNRWSA-N 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 3
- IROWCYIEJAOFOW-RFVHGSKJSA-N 4-[(1s)-1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol;hydrochloride Chemical group Cl.CC(C)NC[C@@H](O)C1=CC=C(O)C(O)=C1 IROWCYIEJAOFOW-RFVHGSKJSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 229940018435 isoproterenol sulfate Drugs 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000006195 ophthalmic dosage form Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000003814 drug Substances 0.000 description 11
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 5
- 229930182837 (R)-adrenaline Natural products 0.000 description 5
- 208000010412 Glaucoma Diseases 0.000 description 5
- 229960005139 epinephrine Drugs 0.000 description 5
- 235000019271 petrolatum Nutrition 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 239000004264 Petrolatum Substances 0.000 description 4
- 230000001800 adrenalinergic effect Effects 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000002997 ophthalmic solution Substances 0.000 description 4
- 229940066842 petrolatum Drugs 0.000 description 4
- 210000001747 pupil Anatomy 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- IROWCYIEJAOFOW-UHFFFAOYSA-N DL-Isoprenaline hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(O)C(O)=C1 IROWCYIEJAOFOW-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 229960001317 isoprenaline Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004493 normal intraocular pressure Effects 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 230000035900 sweating Effects 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- YLXIPWWIOISBDD-NDAAPVSOSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;4-[(1r)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CNC[C@H](O)C1=CC=C(O)C(O)=C1 YLXIPWWIOISBDD-NDAAPVSOSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- 206010015958 Eye pain Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical class CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000035719 Maculopathy Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001384 anti-glaucoma Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229960003157 epinephrine bitartrate Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000734 parasympathomimetic agent Substances 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 229940005542 parasympathomimetics Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- -1 physostigmine Chemical compound 0.000 description 1
- 229960002516 physostigmine salicylate Drugs 0.000 description 1
- HZOTZTANVBDFOF-PBCQUBLHSA-N physostigmine salicylate Chemical compound OC(=O)C1=CC=CC=C1O.C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C HZOTZTANVBDFOF-PBCQUBLHSA-N 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 108010008282 pilocarpine esterase Proteins 0.000 description 1
- 229960002139 pilocarpine hydrochloride Drugs 0.000 description 1
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 201000006366 primary open angle glaucoma Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000025508 response to water Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000330 serious eye damage Toxicity 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940072358 xylocaine Drugs 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26349672A | 1972-06-16 | 1972-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2330338A1 true DE2330338A1 (de) | 1974-01-03 |
Family
ID=23002016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2330338A Pending DE2330338A1 (de) | 1972-06-16 | 1973-06-14 | Okular-hypotensives mittel |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS4948819A (cs) |
| BE (1) | BE801020A (cs) |
| CA (1) | CA1015663A (cs) |
| DD (1) | DD106262A5 (cs) |
| DE (1) | DE2330338A1 (cs) |
| FR (1) | FR2189032B1 (cs) |
| GB (1) | GB1369396A (cs) |
| IE (1) | IE37801B1 (cs) |
| IL (1) | IL42495A (cs) |
| NL (1) | NL7308193A (cs) |
| ZA (1) | ZA733953B (cs) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988007380A1 (en) * | 1987-03-25 | 1988-10-06 | Pharmacia Ab | A composition for the topical treatment of glaucoma or ocular hypertension |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6452727A (en) * | 1988-05-02 | 1989-02-28 | Santen Pharmaceutical Co Ltd | Antiallergic eye drop |
| ZA994264B (en) | 1998-07-01 | 2000-01-25 | Warner Lambert Co | Stereoisomers with high affinity for adrenergic receptors. |
| US7232837B2 (en) | 1999-06-29 | 2007-06-19 | Mcneil-Ppc, Inc. | Stereoisomers with high affinity for adrenergic receptors |
| CA2644488A1 (en) * | 2006-03-24 | 2007-10-04 | National Research Council Of Canada | Anti-diabetic cataract compounds and their uses |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2070173A1 (en) * | 1969-10-29 | 1971-09-10 | Alcon Lab In | Stabilized aqs pyrocatecholamine prepns |
-
1973
- 1973-05-15 CA CA171,427A patent/CA1015663A/en not_active Expired
- 1973-06-12 GB GB2788973A patent/GB1369396A/en not_active Expired
- 1973-06-12 ZA ZA733953A patent/ZA733953B/xx unknown
- 1973-06-13 IL IL42495A patent/IL42495A/en unknown
- 1973-06-13 NL NL7308193A patent/NL7308193A/xx unknown
- 1973-06-14 FR FR7321591A patent/FR2189032B1/fr not_active Expired
- 1973-06-14 DE DE2330338A patent/DE2330338A1/de active Pending
- 1973-06-15 IE IE987/73A patent/IE37801B1/xx unknown
- 1973-06-15 JP JP48066976A patent/JPS4948819A/ja active Pending
- 1973-06-15 BE BE132363A patent/BE801020A/xx unknown
- 1973-06-15 DD DD171583A patent/DD106262A5/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988007380A1 (en) * | 1987-03-25 | 1988-10-06 | Pharmacia Ab | A composition for the topical treatment of glaucoma or ocular hypertension |
Also Published As
| Publication number | Publication date |
|---|---|
| NL7308193A (cs) | 1973-12-18 |
| JPS4948819A (cs) | 1974-05-11 |
| IL42495A (en) | 1976-02-29 |
| FR2189032B1 (cs) | 1977-09-09 |
| GB1369396A (en) | 1974-10-09 |
| BE801020A (fr) | 1973-12-17 |
| CA1015663A (en) | 1977-08-16 |
| DD106262A5 (cs) | 1974-06-12 |
| IL42495A0 (en) | 1973-08-29 |
| AU5642073A (en) | 1974-12-05 |
| ZA733953B (en) | 1974-05-29 |
| IE37801L (en) | 1973-12-16 |
| IE37801B1 (en) | 1977-10-12 |
| FR2189032A1 (cs) | 1974-01-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHJ | Non-payment of the annual fee |