IE48222B1 - Ophthalmic compositions containing colchicine and vinblastine - Google Patents
Ophthalmic compositions containing colchicine and vinblastineInfo
- Publication number
- IE48222B1 IE48222B1 IE908/79A IE90879A IE48222B1 IE 48222 B1 IE48222 B1 IE 48222B1 IE 908/79 A IE908/79 A IE 908/79A IE 90879 A IE90879 A IE 90879A IE 48222 B1 IE48222 B1 IE 48222B1
- Authority
- IE
- Ireland
- Prior art keywords
- colchicine
- vinblastine
- composition
- compositions containing
- isotonic
- Prior art date
Links
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 title claims abstract description 40
- 229960001338 colchicine Drugs 0.000 title claims abstract description 20
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 title claims abstract description 17
- 229960003048 vinblastine Drugs 0.000 title claims abstract description 17
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 title claims abstract description 17
- 239000000203 mixture Substances 0.000 title claims abstract description 12
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 6
- 229930013930 alkaloid Natural products 0.000 claims abstract description 4
- 150000003797 alkaloid derivatives Chemical class 0.000 claims abstract description 4
- 230000004410 intraocular pressure Effects 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000003755 preservative agent Substances 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 3
- 108091006629 SLC13A2 Proteins 0.000 claims description 2
- 230000002335 preservative effect Effects 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 208000010412 Glaucoma Diseases 0.000 abstract description 7
- 239000003937 drug carrier Substances 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract 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 7
- 239000000969 carrier Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 230000003547 miosis Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000243 solution Substances 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
- 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
- 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 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000001179 pupillary effect Effects 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000208327 Apocynaceae Species 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 240000001829 Catharanthus roseus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000189665 Colchicum autumnale Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 206010027646 Miosis Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- BTOSCLDHCFIRKM-ZYQDXHPFSA-N [(1r,4r,5r,7s)-7-[[4-(dimethylamino)phenyl]carbamoyl]-8-(3-methylbutyl)-8-azabicyclo[3.2.1]octan-4-yl] n-pentylcarbamate Chemical compound O=C([C@@H]1[C@H]2CC[C@H]([C@@H](C1)N2CCC(C)C)OC(=O)NCCCCC)NC1=CC=C(N(C)C)C=C1 BTOSCLDHCFIRKM-ZYQDXHPFSA-N 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000013011 aqueous formulation Substances 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
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000006071 cream Substances 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
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- -1 e.g. Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007788 liquid Substances 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
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940096984 ophthalmic cream Drugs 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000001052 transient effect 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
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a therapeutic composition comprising a topically administrable ophthalmic pharmaceutical carrier and an effective amount of an alkaloid selected from colchicine or vinblastine for temporarily alleviating the symptoms of glaucoma in humans.
Description
PATENT APPLICATION BY (777 NELSON RESEARCH & DEVELOPMENT COMPANY, A CORPORATION ORGANISED AND EXISTING UNDER THE LAWS OF THE STATE OF CALIFORNIA, UNITED STATES OF AMERICA, OF 19722 JAMBOREE BOULEVARD, IRVINE, CALIFORNIA, UNITED STATES OF AMERICA.
Print. QOn
The invention relates generally to a composition for reducing intraocular pressure (Ι0Ρ) in humans and animals.
Colchicine is a major alkaloid of Colchicum autumnale L.,
Libaceoe whose extraction procedure is well known in the art. Colchicine has been used heretofore in research on plant genetics and in the therapeutic treatment of gout and Familial Mediterranean Fever.
Vinblastine is an alkaloid isolated from Vinca rosea Linn., Apocynaceae whose extraction procedure is well known in the art. See, for example, U.S. Patent Nos. 3,097,137 and 3,225,030.
Vinblastine has been used heretofore in research and as an antineoplastic agent.
Glaucoma is a condition of the eye characterized by increased intraocular pressure. Untreated, the condition eventually leads to irreversible retinal damage and blindness. Conventional therapy for glaucoma is with pilocarpine and/or epinephrine administered topically several times daily.
One of the problems with many conventional drugs for the treatment of glaucoma is that they decrease the size of the pupil, i.e. they are miotic drugs. This is an undesirable side effect, resulting in temporarily impaired vision.
There has now been discovered a composition for reducing IOP and for treating glaucoma in which there is a minimum of miotic side effects.
The present invention relates to a therapeutic composition comprising a topically administrable ophthalmic pharmaceutical carrier and an effective intraocular pressure reducing amount of an alkaloid
- 2 48222 selected from colchicine or vinblastine.
Suitable ophthalmic carriers are known to those skilled in the art and all such conventional carriers may be employed in the present invention. Thus, a particular carrier may take the form of a sterile, ophthalmic ointment, cream, gel, solution or dispersion. Also included in suitable ophthalmic carriers are slow release polymers, e.g.,
Ocusert polymers, Hydron (Registered Trade Mark) polymers, etc. Stabilizers may also be used such as, for example, chelating agents, e.g., EDTA. Antioxidants may also be used, e.g., sodium bisulfite, sodium thiosulfite, 8-hydroxy quinoline or ascorbic acid. Sterility typically will be maintained by conventional ophthalmic preservatives, e.g., chlorbutanol, benzalkonium chloride, cetylpyridium chloride, phenyl mercuric salts, thimerosal, etc., for aqueous formulations, and used in amounts which are nontoxic and which generally vary from about 0.001 to about 0.1? by weight of the aqueous solution. Conventional preservatives for ointments include methyl and propyl parabens. Typical ointment bases include white petrolatum and mineral oil or liquid petrolatum. However, preserved aqueous carriers are preferred. Solutions may be manually delivered to the eye in suitable dosage form, e.g. eye drops, or delivered by suitable microdrop or spray apparatus typically affording a metered dose of medicament. Examples of suitable ophthalmic carriers include sterile, substantially isotonic, aqueous solutions containing minor amounts, i.e., less than about 5? by weight hydroxypropyImethylcellulose, polyvinyl alcohol, carboxymethylcellulose, hydroxyethylcellulose,glycerine and EDTA. The solutions are preferably maintained at substantially neutral pH and isotonic with appropriate amounts of
- 3 48222 conventional buffers, e.g., phosphate, borate, acetate, tris, etc.
A preferred ophthalmic composition is a preserved aqueous solution containing the following ingredients at the indicated concentration.
Colchicine or Vinblastine
Stabilizer --------per cent
0.1
0.01
0.005
0.05
Preservative --------------------
Buffer -------------------- M
NaC1 q.s. ad isotonic.
Water q.s. ad 100 percent.
The amount of colchicine or vinblastine to be used in reducing intraocular pressure and in the therapeutic treatment of glaucoma will vary with the age of the patient and the severity of the glaucoma. Generally a dose level of one or two drops of the foregoing aqueous solution 1 to 2 times daily would be a suitable dosage amount, though less, i.e., every other day dosage, also may be effective. Generally, the concentration of colchicine or vinblastine will vary from 0.001 to 2 and preferably from 0.01 to 1% by weight.
It has been found that both colchicine and vinblastine administered either topically or by intravitreal injection lowers intraocular pressure in a dose dependent manner. A single topical application of 2 to 5 pg of either of these compounds significantly reduce intraocular pressure for more than 24 hours without signs of ocular irritation or pupillary constriction.
EXAMPLE
A study on the effect of topical administration of colchicine and vinblastine on rabbit intraocular pressure was performed. Different
- 4 48222 amounts of colchicine or vinblastine in phosphate buffer, pH 7.5 were instilled onto the cornea of the test eye of New Zealand white rabbits at time 0, the control eye received an equal volume of the phosphate buffer without colchicine or vinblastine. Ι0Ρ was measured with a pneumatic tonometer and is shown as the difference between the test and control eyes. Five animals were used for each concentration. The results for colchicine are shown in Table 1 below; the results for vinblastine in Table 2.
TABLE 1
Change in IOP (mmHg)
Concentration of Colchicine (%) 0 8 hrs. 24 hrs. 48 hrs. 72 hrs 0.05 0 -0.5 -3 0 - 0.1 0 -0.5 -4 -1.5 - 0.5 0 -1 -9 -3 -0.5 15 2.0 0 +2.5 -9 -6 -4
The highest concentration of colchicine (2%) resulted in an initial rise in IOP, while the remaining concentrations produced a lower· ing of IOP without the initial rise in pressure. The lowest concentration of colchicine (0.05%) showed no ocular irritation of miosis, while the remaining concentrations showed mild ocular irritation and a slight, transient pupillary constriction. The fall in IOP at all doses was slow in onset, becoming apparent 8 hours after administration, reaching a maximum by 24 hours and then slowly returning to normal.
TABLE 2
Change in IOP (mmHg)
Concentration of Vinblastine 0 hrs. 24 hrs. 48 hrs.
0.02
0.1
-1.4
-7.5
-2.1
-9.5
- 5 48223
Claims (6)
1. A therapeutic composition for topical ophthalmic use comprising a topically administrable ophthalmic carrier and an effective, intraocular pressure reducing amount of an alkaloid selected from 5 colchicine or vinblasine.
2. The composition as claimed in Claim 1, wherein the carrier is a preserved, substantially isotonic, aqueous solution.
3. The composition as claimed in Claim 2, wherein an effective amount of colchicine or vinblastine is from 0.001 to 25». 0
4. The composition as claimed in Claim 1, wherein an effective amount of colchicine or vinblastine is from 0.01 to 1%.
5. The composition as claimed in Claim 1 comprising the follow- ing materials in approximately the indicated amounts: Colchicine or Vinblastine percent 0.1 15 Preservative tl 0.005 Stabilizer II 0.01 Buffer M 0.05 2D NaC1 q.s. ad isotonic. Water q.s. ad 100 percent.
6. A therapeutic composition as claimed in any one of claims 1 to 5, substantially as hereinbefore described and exemplified. Dated this 8th day of August 1979. BY: TOMKINS & CO., /Applicants 1 Agents,
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/903,586 US4188394A (en) | 1978-05-08 | 1978-05-08 | Ophthalmic composition and method of use |
| US05/904,586 US4190673A (en) | 1978-05-10 | 1978-05-10 | Colchicine ophthalmic composition and method of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE790908L IE790908L (en) | 1979-11-08 |
| IE48222B1 true IE48222B1 (en) | 1984-10-31 |
Family
ID=27129366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE908/79A IE48222B1 (en) | 1978-05-08 | 1979-08-08 | Ophthalmic compositions containing colchicine and vinblastine |
Country Status (7)
| Country | Link |
|---|---|
| AU (1) | AU527129B2 (en) |
| CA (1) | CA1139668A (en) |
| DE (1) | DE2918264A1 (en) |
| FR (1) | FR2425243A1 (en) |
| GB (1) | GB2020180B (en) |
| IE (1) | IE48222B1 (en) |
| IT (1) | IT1113376B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1170152B (en) * | 1982-07-19 | 1987-06-03 | Lilly Co Eli | IMPROVEMENTS TO OR CONCERNING VINCA-ALCALOID FORMULATIONS |
| GB8710780D0 (en) * | 1987-05-07 | 1987-06-10 | Scras | Opthalmological application of eicosapentaenoic acid |
| IL83086A (en) * | 1987-07-06 | 1991-03-10 | Teva Pharma | Stable,injectable solutions of vincristine salts |
| US4918165A (en) * | 1987-07-16 | 1990-04-17 | Ophthalmic Research Corporation | Mitotic inhibitor and method for preventing posterior lens capsule opacification after extracapsular extraction |
| FR2623089B1 (en) * | 1987-11-13 | 1990-04-27 | Pf Medicament | PHARMACEUTICAL COMPOSITION FOR PARENTERAL ADMINISTRATION OF NAVELBINE |
-
1979
- 1979-04-25 GB GB7914444A patent/GB2020180B/en not_active Expired
- 1979-05-03 AU AU46651/79A patent/AU527129B2/en not_active Ceased
- 1979-05-07 CA CA000327076A patent/CA1139668A/en not_active Expired
- 1979-05-07 DE DE19792918264 patent/DE2918264A1/en not_active Ceased
- 1979-05-07 FR FR7911494A patent/FR2425243A1/en active Granted
- 1979-05-08 IT IT22443/79A patent/IT1113376B/en active
- 1979-08-08 IE IE908/79A patent/IE48222B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR2425243A1 (en) | 1979-12-07 |
| IT7922443A0 (en) | 1979-05-08 |
| GB2020180B (en) | 1982-08-25 |
| AU4665179A (en) | 1979-11-15 |
| DE2918264A1 (en) | 1979-11-15 |
| FR2425243B1 (en) | 1984-07-20 |
| IE790908L (en) | 1979-11-08 |
| IT1113376B (en) | 1986-01-20 |
| CA1139668A (en) | 1983-01-18 |
| GB2020180A (en) | 1979-11-14 |
| AU527129B2 (en) | 1983-02-17 |
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