WO1993006856A1 - Treating ophthalmic fibrosis using interferon-alpha - Google Patents
Treating ophthalmic fibrosis using interferon-alpha Download PDFInfo
- Publication number
- WO1993006856A1 WO1993006856A1 PCT/AU1992/000541 AU9200541W WO9306856A1 WO 1993006856 A1 WO1993006856 A1 WO 1993006856A1 AU 9200541 W AU9200541 W AU 9200541W WO 9306856 A1 WO9306856 A1 WO 9306856A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- interferon
- patient
- treatment
- surgery
- diluent
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to the use of topical interferon-α for the treatment of various forms of fibrosis in and around the eye arising from various ophthalmic diseases and procedures. Specifically the invention relates to alleviation of corneal scarring after laser photoablative refractive keratectomy (PRK). It aslo relates to the alleviation of posterior (lens) capsular opacification after extracapsular cataract surgery with lens implant; the alleviation of wound scarring following glaucoma filtration surgery. Interferon-α may also be used to coat the lens implant prior to or during implantation. It may also possibly be injected into the eye during eye surgery for inhibiting posterior capsule opacification after cataract surgery and in addition may be injected into the vitreous body to prevent retinal fibrosis and proliferative vitreo-retinopathy, and injected subconjunctivally to inhibit fibrosis and scarring following glaucoma filtration surgery.
Description
TREATING OPHTHALMIC FIBROSIS USING INTERFERON-ALPHA
Technical Field
The present invention relates to the use of topical interferon-α for the treatment of various forms of fibrosis in and around the eye arising from various ophthalmic diseases
^ 5 and procedures. Specifically the invention relates to alleviation of corneal scarring after laser photoablative refractive keratectomy (PRK). It also relates to the alleviation of
'" posterior (lens) capsular opacification after extracapsular cataract surgery with lens implant; the alleviation of wound scarring following glaucoma filtration surgery.
Interferon-α may also be used to coat the lens implant prior to or during implantation. It
10 may also possibly be injected into the eye during eye surgery for inhibiting posterior capsule opacification after cataract surgery and in addition may be injected into the vitreous body to prevent retinal fibrosis and proliferative vitreo-retinopathy, and injected subconjunctivally to inhibit fibrosis and scarring following glaucoma filtration surgery.
Background Art 15 In the field of ophthalmic surgery, it is known to use excimer laser photoablative refractive keratectomy to sculpt the cornea of the eye in order to relieve refractive errors (e.g. myopia) and a number of corneal conditions and diseases. Specifically, the 193nm argon fluoride excimer laser is able to discretely remove corneal tissue by photoablation without thermal damage to surrounding tissue. 20 Of major concern is the activation of the stro al keratocytes when a wound is made to the stroma. As is well known, the basic response of wounded tissue is to repair the defect and therefore the ophthalmic surgeon when using this technique is confronted with alteration to the biochemistry, morphologic features and tissue function unpredictability brought about by the wound itself and the healing phenomenon. 25 Therefore, even though excimer laser ablation of corneal tissue appears to be an efficient method of removing tissue with minimal damage to adjacent areas, nevertheless the healing process does not always lead to the preservation of transparent corneal tissue. Previous methods of overcoming this problem have been: application of topical steroids such as prednisolone, prednisolone acetate, prednisolone sodium phosphate, 30 fluoromethalone, fluoromethalone acetate, hydromesterone, dexamethasone, and dexamethasone alcohol. Other compounds tested have been idoxuridine, collagen cross- linkage inhibitors and mitomycin C. f It is an object of this invention to ameliorate the known disadvantages of present techniques when dealing with the wound repair mechanism following photoablative 35 refractive keratectomy.
Interferons are a heterogeneous group of proteins that can inhibit many aspects of the fibrotic response. Originally identified by their well known ability to interfere with the production of viral RNA and protein, they also exert anticellular activities generally considered to be inhibitory, which maybe due to their ability to inhibit the c-myc proto-
oncogene. Type I interferon (viral interferon, interferon-α and -β) is produced in response to viral infection, and type LI (immune interferon, interferon-γ) in response to specific antigens or mitogens. Of the different classes, α-interferon is secreted by leukocytes, β- by fibroblasts and γ- by stimulated lymphocytes. Interferons, particularly interferon-α, have been successfully used in humans for twenty years for the treatment of systemic malignancy.
Considerable interest has recently been shown in the potential of interferon as a treatment for such fibrotic diseases as systemic sclerosis, pulmonary fibrosis and keloid. Fibroblasts are stimulated to produce interferons by many cytokines that mediate wound healing, such as interieukin-l-(LL-l), platelet derived growth factor (PDGF) and tumour necrosis factor (TNF). Interferons inhibit fibroblast chemotaxis and proliferation as well as collagen production, the latter synergistically with TNF-α. Intraperitoneally implanted foreign bodies in mice suffered less encapsulation in the presence of interferon-γ, the capsules having a reduced collagen content. Fibroblast glycosaminoglycan production is inhibited by interferon-α, while collagenase production is increased. This deactivation of activated fibroblasts can persist for a long time after a brief exposure to interferon. Of the different types of interferon, the α- and β- subclasses exhibit a broader antifibrotic spectrum.
The present inventors have recently demonstrated that interferon-α inhibits foetal calf serum and platelet derived growth factor induced proliferation of human tenon's capsule fibroblasts in vitro. They suggest that interferons may prove to be of benefit in the treatment of fibrosis following PRK in particular, and of ocular fibrosis in general.
Disclosure of the Invention According to a first form of this invention, there is provided a method for the treatment of corneal scarring in a patient requiring such treatment, comprising administering to the cornea of said patient an effective amount of interferon-α or a pharmaceutical composition for the treatment of corneal scarring in a patient comprising ϊnterferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient. According to a second form of this invention, there is provided a method for inhibiting opacification of the posterior capsule after extracapsular cataract surgery, in a patient requiring such treatment, comprising administering to the lens capsule of said patient an effective amount of interferon-α or a pharmaceutical composition for this method comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
According to a third form of this invention, there is provided a method for inhibiting wound fibrosis and scarring after glaucoma filtration surgery, in a patient requiring such treatment, comprising administering to the subconjunctival space of said patient an effective amount of interferon-α or a pharmaceutical composition for this
method comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
According to a fourth form of this invention, there is provided a method for inhibiting formation of pre-retinal membranes and proliferative vitreo-retinopathy 5 following retinal detachment surgery and/or vitrectomy, following trauma, and as a result of retinal vascular disease (including diabetes, thalassaemia and retinal vein
^ occlusion) in a patient requiring such treatment, comprising administering to the vitreous body or retina of said patient an effective amount of interferon-α or a pharmaceutical composition for this method comprising interferon-α together with a pharmaceutically
10 acceptable carrier, diluent and/or excipient.
Interferon-α 2 A, interferon-α 2B or interferon-α 2C or any other type of interferon-α may be used in this invention.
The invention also provides novel protein formulations in which the carrier or diluent is a bioerodable polymer, e.g. a polymer ester (polyanhydrine), which may be a 15 copolymer of sebacic acid and bis paracarboxyphenoxybutane; or a poly(ortho) ester.
The method of this, invention inhibits the scarring response following a variety of corneal procedures such as photoablative refractive keratectomy; lamellar keratoplasty; lamellar keratectomy; epikeratoplasty; removal of pterygium and keratomileusis.
Typically, the patient on whom the methods of this invention are used is a human. 20 However, the methods would also be able to be used on other mammals.
The methods of this invention may also inhibit scarring after chemical damage to conjunctiva and comea and may also prevent scarring in pathological conditions such as ocular pemphigoid and StevensJohnson's syndrome, Simplex & Zoster keratitis. It may also inhibit fibrosis in thyroid eye disease, orbital psuedo-tumour and ocular myositis. 25 Preparation of topical composition drops are made up from Intron A powder
(Schering-Plough) or Roferon-A (Roche) to a solution of 1 x 106 IU/mL. Formulation of Intron A is as follows: α- 2b interferon solution Dibasic sodium phosphate, anhydrous, USP 30 Monosodium phosphate, monohydrate, USP
Glycine, ph. eur. Human albumin solution, ph. eur. ♦ Water for injection, ph. eur.
Drops base may be hypromellose or polyvinyl alcohol for dilution to 106 IU/mL. "t 35 The composition of the present invention may be administered topically as a solution, ointment, or within a collagen shield or similar dissolving corneal contact protective dressing containing conventional, non-toxic, pharmaceutically acceptable carriers, diluents and/or excipients as desired, or by direct injection.
The dosage range of interferon-α may be between about 50,000 and 50 x 106 IU
and may be between about 1 x 106 to 20 x 106 IU/mL. Preferably the dosage is between about lxlO6 and about lOxlO6 IU/mL. The interferon-α may be administered in 50 μL drops, four times a day for six weeks; or preferably two times a day for one week. Interferon-α may also be administered two times a day for three days or one drop hourly for three days. This dosage range is applicable to the first, second and third embodiments of the invention.
When applied according to the fourth embodiment the interferon-α is given by intravitreal injection within the range of 50,000 to 5.0 x 106 IU/O.lmL.
The compositions of this invention may also contain a slow release polymer. The pharmaceutically acceptable carriers, diluents and/or excipients are those well known in the art of ophthalmic surgery and comprise the following: hydroxyethyl cellulose, hypromellose, polyvinyl alcohol, gelatin, polyquad, dextran, castor oil or other vegetable oil e.g. sesame, inert soft white paraffin, liquid paraffin, anhydrous lanolin, sodium hyalusonate, methyl cellulose, potassium sorbate, polysorbate; or sodium chloride, sodium phosphate, buffers hydrochloric acid bicarbonate, Na citrate (citric acid) boric acid in purified water. They may also be biodegradable polymer esters (polyanhydrines) e.g. sebacic acid and bis paracarboxyphenoxybutane, which are employed in the novel formulations of the invention.
The compositions may also contain preservatives and antiseptics such as: thiomersal, phenyl mercuric acetate, benzylalkonium chloride, disodium edetate, sodium metabisulfite, polymercuric nitrate, chlorobutol, hyloxapol, povidone, propyl hydroxy benzoate, methyl hydroxy benzoate.
It is preferable that the composition of this invention be applied to the cornea immediately following photoablative refractive keratectomy. As a drop, ointment or collagen shield etc. Where the interferon is applied as a drop, it is preferably to treat the eye thus, four to eight times a day for up to about 6 weeks.
The corneal response may be modified by the pre-treatment with interferon α drops before PRK. It may also be modified by pre-treatment with steroid drops.
The interferon-α may be prepared from natural sources or may be prepared by recombinant DNA techniques. All of these techniques would be well known to one skilled in this art.
Best Mode and Other Modes for Carrying Out the Invention An effective amount of interferon-α-2b to prevent corneal scarring after photoablative refractive keratectomy is administered topically to the cornea which has been subjected to this procedure.
The present invention will now be described with reference to the following examples which should not be construed as limiting on the scope thereof.
Example 1 Preparation of interferon α-2B topical composition Preparation of topical composition drops are made up from Intron A powder (Schering-Plough) to a solution of 1 x 106 IU/mL. Formulation of Intron A is as follows: α-2b interferon solution Dibasic sodium phosphate, anhydrous, USP
Monosodium phosphate, monohydrate, USP Glycine, ph. eur. Human albumin solution, ph. eur.
Water for injection, ph. eur. The drops base is hypromellose or polyvinyl alcohol for dilution to 106 IU/mL.
Example 2 The composition of this invention is applied to the cornea immediately following photoablative refractive keratectomy, As a drop, ointment or collagen shield etc. Where the interferon is applied as a drop, it is preferable to treat the eye thus, four times a day for up to about 6 weeks.
The corneal response may be modified by the pre-treatment with interferon-α-2b drops before PRK. It may also be modified by pre-treatment with steroid drops. Industrial Applicability
It should be clear that the method of treatment of this invention will find wide use in the veterinary and medical fields.
The foregoing describes only some embodiments of the present invention and modifications obvious to those skilled in the art can be made thereto without departing from the scope of the invention.
References Gipson IK (1990) Archives of Opthalmology 108 1539. Cintron C (1990) Archives of Opthalmology 108 1540. Binder PS (1990) Archives of Opthalmology 108 1541.
Claims
1. Use of interferon-α for treating corneal scarring, for inhibiting opacification ofthe posterior capsule after extracapsular cataract surgery, for inhibiting wound fibrosis
5 and scarring after glaucoma filtration surgery, or for inhibiting formation of pre-retinal membranes and proliferative vitreo-retinopathy.
2. Use according to claim 1 wherein the dosage of interferon-α is between about
50,000 and 50 x 106 IU/mL.
3. Use according to claim 2 wherein the dosage unit is between about 1 x 106 to 10 20 x 106 IU/mL.
4. Use according to claim 3 wherein the dosage range is between about 1 x 106 and about 10 x 106 IU/mL.
5. Use according to any one of claims 1 to 4 wherein the interferon-α is interferon-α-2A. 5
6. Use according to any one of claims 1 to 4 wherein interferon-α is interferon- α-2B.
7. Use according to any one of claims 1 to 4 wherein interferon-α is interferon- α-2C.
8. A process for preparing a composition of interferon-α comprising 0 formulating interferon-α together with a pharmaceutically carrier, diluent and/or excipient.
9. The process of claim 8 wherein the carrier, diluent and/or excipient is a bioerodable polymer.
10. A process of claim 9 wherein the bioerodable polymer is a polymer ester 5 (polyanhydrine) or a poly(ortho) ester.
11. A process of claim 10 wherein the polyanhydrine is a copolymer of sebacic acid and bisparacarboxyphenoxybutane.
12. A method for the treatment of corneal scarring in a patient requiring such treatment, comprising administering to the cornea of said patient an effective amount of 0 interferon-α or a pharmaceutical composition for the treatment of corneal scarring in a patient comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
13. A method for inhibiting opacification of the posterior capsule after extracapsular cataract surgery, in a patient requiring such treatment, comprising administering to the lens capsule of said patient an effective amount of interferon-α or a pharmaceutical composition for this method comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
14. A method for inhibiting wound fibrosis and scarring after glaucoma filtration surgery, in a patient requiring such treatment, comprising administering to the subconjunctival space of said patient an effective amount of interferon-α or a pharmaceutical composition for this method comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
15. The method according to any one of claims 12 to 14 wherein the dosage of interferon-α range is between about 50,000 and 50 x 106 IU/mL.
16. The method according to claim 15 wherein the dosage unit is between about 1 x 106 to 20 x 106 IU/mL.
17. The method according to claim 16 wherein the dosage range is between about 1 x 106 and about 10 x 106 IU/mL.
18. The method according to any one of claims 14 to 17 wherein the interferon-α may be administered in about 50μL drops four times a day for six weeks.
19. The method according to claim 18 wherein the interferon-α may be administered two times a day for three days.
20. The method according to any one of claims 14 to 17 wherein the interferon-α is administered as one drop hourly for three days.
21. A method for inhibiting formation of pre-retinal membranes and proliferative vitreo-retinopathy following retinal detachment surgery and/or vitrectomy, following trauma, and as a result of retinal vascular disease (including diabetes, thalassaemia and retinal vein occlusion) in a patient requiring such treatment, comprising administering to the vitreous body or retina of said patient an effective amount of interferon-α or a pharmaceutical composition for this method comprising interferon-α together with a pharmaceutically acceptable carrier, diluent and/or excipient.
22. The method according to claim 21 wherein the interferon-α is given by intravitreal injection within the range of about 50,000 to 5.0 x 106 IU/O.lmL.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP92921557A EP0607275A4 (en) | 1991-10-11 | 1992-10-12 | Treating ophthalmic fibrosis using interferon-alpha. |
| AU27748/92A AU669132B2 (en) | 1991-10-11 | 1992-10-12 | Treating ophthalmic fibrosis using interferon-alpha |
| JP5506481A JPH07501320A (en) | 1991-10-11 | 1992-10-12 | Treatment of ocular fibrosis with interferon alpha |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPK886591 | 1991-10-11 | ||
| AUPK8865 | 1991-10-11 | ||
| AUPK9080 | 1991-10-22 | ||
| AUPK908091 | 1991-10-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993006856A1 true WO1993006856A1 (en) | 1993-04-15 |
Family
ID=25644122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/AU1992/000541 WO1993006856A1 (en) | 1991-10-11 | 1992-10-12 | Treating ophthalmic fibrosis using interferon-alpha |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0607275A4 (en) |
| JP (1) | JPH07501320A (en) |
| CA (1) | CA2120950A1 (en) |
| WO (1) | WO1993006856A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996029092A1 (en) * | 1995-03-17 | 1996-09-26 | Toray Industries, Inc. | Corneal vascularization inhibitor |
| EP0797998A1 (en) * | 1995-11-17 | 1997-10-01 | Toray Industries, Inc. | Endothelial cell protective |
| WO1998029069A2 (en) * | 1997-01-02 | 1998-07-09 | Allergan Sales, Inc. | Method for changing the refractive power of an eye |
| WO2006136116A1 (en) * | 2005-06-24 | 2006-12-28 | Centro De Ingenieria Genetica Y Biotecnologia | Use of interferon-alpha in order to obtain a compound for the treatment of optical neuromyelitis |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2243161A1 (en) * | 1996-11-22 | 1998-05-28 | Toray Industries, Inc. | Use of interferon-beta to treat retinal edema |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0082481A1 (en) * | 1981-12-23 | 1983-06-29 | Schering Corporation | Stabilised alpha-interferon formulations and their preparation |
| AU6829287A (en) * | 1986-02-05 | 1987-08-06 | Dr. Karl Thomae Gmbh | Stabilised formulations of alpha-interferon |
| AU7730787A (en) * | 1986-08-21 | 1988-02-25 | Dr. Karl Thomae Gmbh | Formulations of alpha-interferons |
| WO1988003411A1 (en) * | 1986-11-06 | 1988-05-19 | Amarillo Cell Culture Company, Inc. | Improved interferon therapy |
| AU6820190A (en) * | 1988-01-25 | 1991-03-14 | Baker Norton Pharmaceuticals, Inc. | Method of treating fibrotic disorders |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6391331A (en) * | 1986-10-03 | 1988-04-22 | Senjiyu Seiyaku Kk | Ophthalmic aqueous composition |
-
1992
- 1992-10-12 JP JP5506481A patent/JPH07501320A/en active Pending
- 1992-10-12 CA CA002120950A patent/CA2120950A1/en not_active Abandoned
- 1992-10-12 EP EP92921557A patent/EP0607275A4/en not_active Withdrawn
- 1992-10-12 WO PCT/AU1992/000541 patent/WO1993006856A1/en not_active Application Discontinuation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0082481A1 (en) * | 1981-12-23 | 1983-06-29 | Schering Corporation | Stabilised alpha-interferon formulations and their preparation |
| AU6829287A (en) * | 1986-02-05 | 1987-08-06 | Dr. Karl Thomae Gmbh | Stabilised formulations of alpha-interferon |
| AU7730787A (en) * | 1986-08-21 | 1988-02-25 | Dr. Karl Thomae Gmbh | Formulations of alpha-interferons |
| WO1988003411A1 (en) * | 1986-11-06 | 1988-05-19 | Amarillo Cell Culture Company, Inc. | Improved interferon therapy |
| AU6820190A (en) * | 1988-01-25 | 1991-03-14 | Baker Norton Pharmaceuticals, Inc. | Method of treating fibrotic disorders |
Non-Patent Citations (1)
| Title |
|---|
| See also references of EP0607275A4 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996029092A1 (en) * | 1995-03-17 | 1996-09-26 | Toray Industries, Inc. | Corneal vascularization inhibitor |
| EP0797998A1 (en) * | 1995-11-17 | 1997-10-01 | Toray Industries, Inc. | Endothelial cell protective |
| EP0797998A4 (en) * | 1995-11-17 | 2003-01-15 | Toray Industries | Endothelial cell protective |
| WO1998029069A2 (en) * | 1997-01-02 | 1998-07-09 | Allergan Sales, Inc. | Method for changing the refractive power of an eye |
| WO1998029069A3 (en) * | 1997-01-02 | 1998-10-08 | Allergan Inc | Method for changing the refractive power of an eye |
| WO2006136116A1 (en) * | 2005-06-24 | 2006-12-28 | Centro De Ingenieria Genetica Y Biotecnologia | Use of interferon-alpha in order to obtain a compound for the treatment of optical neuromyelitis |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07501320A (en) | 1995-02-09 |
| CA2120950A1 (en) | 1993-04-15 |
| EP0607275A1 (en) | 1994-07-27 |
| EP0607275A4 (en) | 1995-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5811446A (en) | Prophylactic and therapeutic methods for ocular degenerative diseases and inflammations and histidine compositions therefor | |
| Freeman et al. | Prevalence, pathophysiology, and treatment of rhegmatogenous retinal detachment in treated cytomegalovirus retinitis | |
| Fujitani et al. | Corneoscleral ulceration and corneal perforation after pterygium excision and topical mitomycin C therapy | |
| EP0179477B1 (en) | Fibronectin preparations | |
| JPH10158188A (en) | Composition for treating cornea | |
| CA2138644A1 (en) | Method of treating ophthalmic disorders using tgf-.beta. | |
| Phinney et al. | Corneal edema related to accidental Hibiclens exposure | |
| US7977385B2 (en) | Agents for corneal or intrastromal administration to treat or prevent disorders of the eye | |
| Pfister | Clinical measures to promote corneal epithelial healing | |
| AU2009201897B2 (en) | Agents for corneal or intrastromal administration to treat or prevent disorders of the eye | |
| Gelender | Bacterial endophthalmitis following cutting of sutures after cataract surgery | |
| WO1993006856A1 (en) | Treating ophthalmic fibrosis using interferon-alpha | |
| US5863530A (en) | Treating ophthalmic fibrosis using interferon-α | |
| WO2018066963A1 (en) | Pharmaceutical composition for treating corneal injury containing 8-oxo-deoxyguanosine or pharmaceutically acceptable salt thereof as active ingredient | |
| AU2774892A (en) | Treating ophthalmic fibrosis using interferon-alpha | |
| Ohashi | Treatment of herpetic keratitis with acyclovir: benefits and problems | |
| JPH06271478A (en) | Agent for treating dry eye | |
| JPH08503968A (en) | Composition containing growth factor and antimetabolite | |
| US20140112902A1 (en) | Methods for treatment of inflammatory and infectious diseases | |
| EP0080032A2 (en) | Pharmaceutical preparation for treating herpetic lesions | |
| US5948403A (en) | Corneal angiogenesis inhibitor | |
| Genvert et al. | Treatment of marginal corneal ulcers with cryotherapy and conjunctival recession or resection | |
| JP3118584B2 (en) | Postoperative astigmatism prevention agent | |
| EP0885612A1 (en) | Pirenoxine for the topical treatment of inflammatory conditions | |
| JPH0881389A (en) | Agent for multiplying pigment epithelial cell of retina |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO PL RO RU SD SE UA US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL SE BF BJ CF CG CI CM GA GN ML MR SN TD TG |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2120950 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1992921557 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1992921557 Country of ref document: EP |
|
| ENP | Entry into the national phase |
Ref document number: 1994 211655 Country of ref document: US Date of ref document: 19940801 Kind code of ref document: A |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1992921557 Country of ref document: EP |