US3467756A - Composition and method for treating glaucoma - Google Patents
Composition and method for treating glaucoma Download PDFInfo
- Publication number
- US3467756A US3467756A US623540A US3467756DA US3467756A US 3467756 A US3467756 A US 3467756A US 623540 A US623540 A US 623540A US 3467756D A US3467756D A US 3467756DA US 3467756 A US3467756 A US 3467756A
- Authority
- US
- United States
- Prior art keywords
- glaucoma
- epoxy
- opthalmic
- hydroxyimino
- compositions
- 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.)
- Expired - Lifetime
Links
- 239000000203 mixture Substances 0.000 title description 21
- 208000010412 Glaucoma Diseases 0.000 title description 10
- 238000000034 method Methods 0.000 title description 9
- 239000004593 Epoxy Substances 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 230000000699 topical effect Effects 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 230000003547 miosis Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000004410 intraocular pressure Effects 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000150 Sympathomimetic Substances 0.000 description 5
- 230000001384 anti-glaucoma Effects 0.000 description 5
- 239000002220 antihypertensive agent Substances 0.000 description 5
- 229960005139 epinephrine Drugs 0.000 description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000003604 miotic agent Substances 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 3
- -1 3-dimethylaminopropyl Chemical group 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940096826 phenylmercuric acetate Drugs 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000001975 sympathomimetic effect Effects 0.000 description 3
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 206010027646 Miosis Diseases 0.000 description 2
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 2
- 229910021538 borax Inorganic materials 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
- 239000006172 buffering agent Substances 0.000 description 2
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- QPJORFLSOJAUNL-UHFFFAOYSA-N dibenzo[a,d][7]annulene Chemical compound C1=CC2=CC=CC=C2CC2=CC=CC=C21 QPJORFLSOJAUNL-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940039009 isoproterenol Drugs 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 229960001416 pilocarpine Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000001179 pupillary effect Effects 0.000 description 2
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 1
- GBEPCNLTEZAPMJ-UHFFFAOYSA-N 8-hydroxy-1h-quinolin-2-one;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=C(O)C2=NC(O)=CC=C21 GBEPCNLTEZAPMJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010022949 Iris cyst Diseases 0.000 description 1
- 206010043087 Tachyphylaxis Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940055075 anticholinesterase parasympathomimetics Drugs 0.000 description 1
- 239000000030 antiglaucoma agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- ZXZKYYHTWHJHFT-UHFFFAOYSA-N quinoline-2,8-diol Chemical compound C1=CC(=O)NC2=C1C=CC=C2O ZXZKYYHTWHJHFT-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009827 uniform distribution Methods 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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
- 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
Definitions
- the present invention relates to topical opthalmic compositions useful in the treatment of glaucoma. More particularly, this invention relates to anti-glaucoma agents which effectively lower intraocular pressure and to methods for the preparation and administration of such compositions.
- a further object is to topically administer such compositions to the eye in a dosage form that will significantly lower intraocular pressure while achieving the pupillary goals of a submaximally dilated and mobile pupil, retaining sensitivity to stimulation by light.
- compositions of this invention contain one of the following compounds as novel intraocular hypotensive agents:
- compositions of this invention wherein the novel hypotensive agents form the only active ingredient effectively lower intraoclar tension for some purposes it may be desirable to combine treatment with exogenous sympathomirnetic amines.
- the sympathomimetic amine can be administered with the intraocular hypotensive agent of this invention in a single vehicle in dosages which effectively lower intraocular pressure.
- exemplary of such sympathomimetic amines are epinephrine, norepinephrine and isoproterenol.
- the sympathomimetic amine can be administered following instillation of the novel hypotensive agent of this invention.
- compositions of this invention are administered topically to the eye, either in the form of opthalmic solutions, or as opthalmic ointments.
- Formulations are herein expressed as percent weight by volume and generally the dosages for the intraocular hypotensive agent fall within the range of 0.01 to 0.02 percent. Higher dosages, as for example, up to about 0.2 percent, or lower dosages can be employed, provided the dose is effective in lowering intraocular pressure, is non-irritating and achieves the desired pupillary goals previously set forth.
- compositions of this invention are incorporated into a sterile opthalmic vehicle.
- sterile opthalmic vehicles are Well known in the art and are fully described in such standard reference works as Remingtons Pharmaceutical Sciences, Martin and Cook, Mack Publishing Co., Easton, 13th 3 edition (1965). The following is a suitable example. (The percentages in the following examples refer to a percent weight by volume.)
- the 8-hydroxyquinolone and the sodium bisulfite act as anti-oxidants and can vary tenfold (the former up to about 0.1% and the latter down to about 0.03%.)
- any opthalmic anti-oxidant can be employed. These are more fully described in Remington (supra).
- Phenyl mercuric acetate is employed as a preservative. Any preservative suitable for opthalmic formulation such as those described in Remington (supra) can be employed.
- pH of the foregoing sterile vehicle is adjusted using base or acid it should be recognized that standard buffering agents such as those described in Remington (supra) or in the Merck Index, volume 7 (1960), so long as these buffering agents are suitable for opthalmic formulation, can be utilized. Thus a pH range from about 3.5-8 can be employed, although pH within the physiological range is preferred. When employing a buffered system it is preferred to utilize a pH of about 6.0 to about 8. With a buffered system pH is conventionally adjusted by adjusting the concentration and at the time altering the ratio of the buffered tonicity so as to maintain an isotonic solution.
- buffers can be used at varying pH, when pH is less than 6.0, sodium hydroxide or hydrochloric acid can conveniently be employed to adjust the pH. When using a buffered system it is preferred to adjust the range to that of the physiological pH range of about 6 to 7.5 or 8. US. Patent 3,149,035 sets forth suitable sterile vehicles for use, especially when a catechol amine, such as epinephrine, is employed in the compositions of this invention.
- compositions of this invention can also be administered as opthalmic ointments. These are compounded, for example, by mixing finely milled powdered ingredients with a small amount of white petrolatum and levigating or otherwise mixing until a uniform distribution is achieved. The balance of white petrolatum is added by geometric addition until the desired dosage form is made.
- An anti-glaucoma topical opthalmic composition comprising a topical opthalmic vehicle and 0.01 to 0.2% of a member selected from the group consisting of 10,11- dihydro 5 (3-dimethylaminopropyl)-5,10-epoxy-5H-dibenzo[a,d]cycloheptene-1l-hydroxy-imino, trans 10,1 1-dihydro 5-(3-methylaminopropyl)-5,10-epoxy-1l-hydroxy- 5H-dibenzo[a,d]cycloheptene and a non-toxic acid addition salt thereof.
- a method for lowering intraocular pressure which comprises applying topically to the eye an effective amount of a composition comprising a topical opthalmic vehicle and 0.01 to 0.2% of a member selected from the group consisting of 10,11 dihydro-5-(3-dimethylaminopropyl)- 5,10 epoxy 5H-dibenzo[a,d]cycloheptene-ll-hydroxyimino, trans 10,11 dihydro-5-(3-methylaminopropyl)-5, 10 epoxy-11-hydroxy-5H-dibenzo[a,d]cycloheptene and a non-toxic acid addition salt thereof.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (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 |
|---|---|---|---|
| US62354067A | 1967-03-16 | 1967-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3467756A true US3467756A (en) | 1969-09-16 |
Family
ID=24498471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US623540A Expired - Lifetime US3467756A (en) | 1967-03-16 | 1967-03-16 | Composition and method for treating glaucoma |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3467756A (en:Method) |
| BE (1) | BE712259A (en:Method) |
| DE (1) | DE1667898A1 (en:Method) |
| FR (1) | FR7841M (en:Method) |
| GB (1) | GB1174882A (en:Method) |
| IE (1) | IE31971B1 (en:Method) |
| IL (1) | IL29570A (en:Method) |
| NL (1) | NL6802823A (en:Method) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993018762A2 (en) | 1992-03-19 | 1993-09-30 | Allergan, Inc. | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (gaba) agonists |
| US5716952A (en) * | 1992-03-18 | 1998-02-10 | Allergan | Method for reducing intraocular pressure in the mammalian eye by administration of muscarinic antagonists |
| US5891911A (en) * | 1995-07-28 | 1999-04-06 | Allergan | Method for reducing intraocular pressure in the mammalian eye by administration of calcium chelators |
| US6350780B1 (en) | 1995-07-28 | 2002-02-26 | Allergan Sales, Inc. | Methods and compositions for drug delivery |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3264342A (en) * | 1963-05-24 | 1966-08-02 | Geigy Chem Corp | Derivatives of 5h-dibenzo[a, d] cycloheptene |
| US3336340A (en) * | 1963-11-29 | 1967-08-15 | Rohm & Haas | Benzopyrans and process for the preparation thereof |
-
1967
- 1967-03-16 US US623540A patent/US3467756A/en not_active Expired - Lifetime
-
1968
- 1968-02-28 NL NL6802823A patent/NL6802823A/xx unknown
- 1968-03-04 IL IL29570A patent/IL29570A/en unknown
- 1968-03-04 IE IE249/68A patent/IE31971B1/xx unknown
- 1968-03-12 GB GB01980/68A patent/GB1174882A/en not_active Expired
- 1968-03-15 FR FR144115A patent/FR7841M/fr not_active Expired
- 1968-03-15 DE DE19681667898 patent/DE1667898A1/de active Pending
- 1968-03-15 BE BE712259D patent/BE712259A/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3264342A (en) * | 1963-05-24 | 1966-08-02 | Geigy Chem Corp | Derivatives of 5h-dibenzo[a, d] cycloheptene |
| US3336340A (en) * | 1963-11-29 | 1967-08-15 | Rohm & Haas | Benzopyrans and process for the preparation thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5716952A (en) * | 1992-03-18 | 1998-02-10 | Allergan | Method for reducing intraocular pressure in the mammalian eye by administration of muscarinic antagonists |
| WO1993018762A2 (en) | 1992-03-19 | 1993-09-30 | Allergan, Inc. | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (gaba) agonists |
| US6077839A (en) * | 1992-03-19 | 2000-06-20 | Allergan Sales, Inc. | Method for reducing intraocular pressure in the mammalian eye by administration of gamma aminobutyric acid (GABA) agonists |
| US5891911A (en) * | 1995-07-28 | 1999-04-06 | Allergan | Method for reducing intraocular pressure in the mammalian eye by administration of calcium chelators |
| US6350780B1 (en) | 1995-07-28 | 2002-02-26 | Allergan Sales, Inc. | Methods and compositions for drug delivery |
Also Published As
| Publication number | Publication date |
|---|---|
| IE31971L (en) | 1968-09-16 |
| GB1174882A (en) | 1969-12-17 |
| DE1667898A1 (de) | 1971-07-22 |
| FR7841M (en:Method) | 1970-05-25 |
| BE712259A (en:Method) | 1968-09-16 |
| IE31971B1 (en) | 1973-03-07 |
| IL29570A (en) | 1971-07-28 |
| NL6802823A (en:Method) | 1968-09-17 |
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