CA2120950A1 - Treating ophthalmic fibrosis using interferon-alpha - Google Patents
Treating ophthalmic fibrosis using interferon-alphaInfo
- Publication number
- CA2120950A1 CA2120950A1 CA002120950A CA2120950A CA2120950A1 CA 2120950 A1 CA2120950 A1 CA 2120950A1 CA 002120950 A CA002120950 A CA 002120950A CA 2120950 A CA2120950 A CA 2120950A CA 2120950 A1 CA2120950 A1 CA 2120950A1
- Authority
- CA
- Canada
- Prior art keywords
- interferon
- alpha
- treatment
- surgery
- patient
- 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.)
- Abandoned
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
Abstract
The present invention relates to the use of topical interferon-.alpha. 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-.alpha. 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.
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-.alpha. 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
W093/06856 2 ~ 2 0 ~1 i O pcr/Au92/oos41 TREATING OPHTHALMIC FIBROSIS USING INTERFERON-ALPHA
Technical Field The present invention relates to the use of topical interferon-a for the treatment of various forms of fibrosis in and around the eye arising from various ophthalmic diseases s 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-a may also be used to coat the lens implant prior to or during implantation. lt 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 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 discrete1y remove corneal tissue by photoablation without thermal damage to surrounding tissue.
20 Of major concern is the acdvation of the stromal keratocytes when a wound is made to the stroma. As is well known, the basic response of wounded tissue is to repair *e defect and therefore the ophthalmic surgeon when using *is teclLnique is confronted wi* alteration to the biochemistry, morphologic features~ and tissue function ~ unpredictability brought about by the wound itself and ~the healing phenomenon.
- 2s Therefore, even though excimer laser ablation of cornea1 tissue appears to ~e an efficient method of removing tissue with minimal damage to adjacent arças, nevertheless the healing pro~ess does not always lead to the preserva~on 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-iinkage inhibitors and mitomycin (: .
It is an object of this invention to ameliorate the known disadvantages of present techniques when dealing with the wound repair mechanism fiollowing photoablative35 refractive keratectomy.
Interfe~ons are a heterogeneous group of proteins that can inhibit many aspects of ~- the fibrotic response. Originally identified by their well known ability to interfere wieh ; ~ the p oduction 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-WO 93/06856 pcr/Aus2~oo54l 2~9~ 2 oncogene. Type I interferon (viral interferon, interferon-a and -~) is produced in response to viral infection, and type II (immune interferon, interferon-~) in response to specific antigens or mitogens. Of the different classes, a-interferon is secreted by leukocytes, ~ by fibroblasts and ~ by stimulated Iymphocytes. lnterferons, s particularly interferon-a, 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.
Fib~oblasts are stimulated to produce interferons by many cytokines that mediate wound 10 healing, such as interleukin-l-(IL-1), platelet derived growth factor (PDGF) and tumour necrosis factor (TNF). Interferons inhibit fibroblast chemotaxis and proliferation as well as collagen production, the latter syner~istically with TNF-a. lntraperitoneallyimplanted foreign bodies in mice suffered less encapsulation in the presence of interferon- y, the capsules having a reduced collagen content. Pibroblast 5 glycosaminoglycan production is inhibited by interferon-a, 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 a- and ,B
subclasses exhibit a broader antifibrotic spectrum.
The present inventors have recently demonstrated that interferon-a inhibits foetal 20 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 particularj 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 2s treatment of corneal scar~ing in a patient requiring such treatment, comprlsing adn~inistering to the cornea of said patient an effective amount of interferon-oc or a pharmaceutical compositivn for the treatment of corneal scarring in a patient comprisîng interfer~n-a together with a phanna~utically acceptable carrier7 diluent and/or excipient.
30 According to a second form of this invention, there is provided a method for inhibiting opacificatios~. of the posterior c~psule after extracapsular ca~ract surgery, in a patient requiring such treatment, comprising administering to the lens capsule of said patient an effective amount of interferon-(x or a pharmaceutical composition for this method comprising interferon-a together with a pharmaceutically acceptable carrier, 35 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 effe~tive amount of interferon-a or a pharrnaceutical composition for this WO 93/06856 ~ ~ 2 ~ 9 ~ ~ pcr/Aug2/oos41 method comprising interferon-o~ together with a pharmaceutically accepeable carrier, diluent and/or excipient.
According to a fourth form of this invention, therç is provided a method for inhibiting formation of pre-retinal membranes and proliferative vitreo-retinopathy 5 following retinal detachment surgery and/or vitrectomy, following traumat 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-a or a pharrnaceutical composition for this method comprising interferon-oc together with a pharmaceutically lo acceptable carrier, diluent and/or excipient.
Interferon-a 2A, interferon-a 2B or interferon-a 2C or any other type of interferon-a 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 i~ a human.
20 However, the methods would also be able to be used on other mammals. r The methods of this invention may also inhibit scarring after chemical damage toconjunctiva and cornea 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:
a- 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.
Technical Field The present invention relates to the use of topical interferon-a for the treatment of various forms of fibrosis in and around the eye arising from various ophthalmic diseases s 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-a may also be used to coat the lens implant prior to or during implantation. lt 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 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 discrete1y remove corneal tissue by photoablation without thermal damage to surrounding tissue.
20 Of major concern is the acdvation of the stromal keratocytes when a wound is made to the stroma. As is well known, the basic response of wounded tissue is to repair *e defect and therefore the ophthalmic surgeon when using *is teclLnique is confronted wi* alteration to the biochemistry, morphologic features~ and tissue function ~ unpredictability brought about by the wound itself and ~the healing phenomenon.
- 2s Therefore, even though excimer laser ablation of cornea1 tissue appears to ~e an efficient method of removing tissue with minimal damage to adjacent arças, nevertheless the healing pro~ess does not always lead to the preserva~on 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-iinkage inhibitors and mitomycin (: .
It is an object of this invention to ameliorate the known disadvantages of present techniques when dealing with the wound repair mechanism fiollowing photoablative35 refractive keratectomy.
Interfe~ons are a heterogeneous group of proteins that can inhibit many aspects of ~- the fibrotic response. Originally identified by their well known ability to interfere wieh ; ~ the p oduction 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-WO 93/06856 pcr/Aus2~oo54l 2~9~ 2 oncogene. Type I interferon (viral interferon, interferon-a and -~) is produced in response to viral infection, and type II (immune interferon, interferon-~) in response to specific antigens or mitogens. Of the different classes, a-interferon is secreted by leukocytes, ~ by fibroblasts and ~ by stimulated Iymphocytes. lnterferons, s particularly interferon-a, 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.
Fib~oblasts are stimulated to produce interferons by many cytokines that mediate wound 10 healing, such as interleukin-l-(IL-1), platelet derived growth factor (PDGF) and tumour necrosis factor (TNF). Interferons inhibit fibroblast chemotaxis and proliferation as well as collagen production, the latter syner~istically with TNF-a. lntraperitoneallyimplanted foreign bodies in mice suffered less encapsulation in the presence of interferon- y, the capsules having a reduced collagen content. Pibroblast 5 glycosaminoglycan production is inhibited by interferon-a, 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 a- and ,B
subclasses exhibit a broader antifibrotic spectrum.
The present inventors have recently demonstrated that interferon-a inhibits foetal 20 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 particularj 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 2s treatment of corneal scar~ing in a patient requiring such treatment, comprlsing adn~inistering to the cornea of said patient an effective amount of interferon-oc or a pharmaceutical compositivn for the treatment of corneal scarring in a patient comprisîng interfer~n-a together with a phanna~utically acceptable carrier7 diluent and/or excipient.
30 According to a second form of this invention, there is provided a method for inhibiting opacificatios~. of the posterior c~psule after extracapsular ca~ract surgery, in a patient requiring such treatment, comprising administering to the lens capsule of said patient an effective amount of interferon-(x or a pharmaceutical composition for this method comprising interferon-a together with a pharmaceutically acceptable carrier, 35 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 effe~tive amount of interferon-a or a pharrnaceutical composition for this WO 93/06856 ~ ~ 2 ~ 9 ~ ~ pcr/Aug2/oos41 method comprising interferon-o~ together with a pharmaceutically accepeable carrier, diluent and/or excipient.
According to a fourth form of this invention, therç is provided a method for inhibiting formation of pre-retinal membranes and proliferative vitreo-retinopathy 5 following retinal detachment surgery and/or vitrectomy, following traumat 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-a or a pharrnaceutical composition for this method comprising interferon-oc together with a pharmaceutically lo acceptable carrier, diluent and/or excipient.
Interferon-a 2A, interferon-a 2B or interferon-a 2C or any other type of interferon-a 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 i~ a human.
20 However, the methods would also be able to be used on other mammals. r The methods of this invention may also inhibit scarring after chemical damage toconjunctiva and cornea 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:
a- 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.
3~ 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-o~ may be between about 50,000 and 50 x 106 IU
and may be between about I x 106 to 20 x lo6 lU/mL. Preferably the dosage is between about lx106 and about 10X106 IU/mL. The interferon-o~ may be administered in 50 ~L
drops, four times a day for six weeks; or preferably two times a day for one week.
Interferon-o~ may also be administered two times a day for three days or one drop hourly 5 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-a is given by intravitreal injection within the range of 50,000 to 5.0 x 106 IU/0.lmL.
The compositions of this invention may also contain a slow release polymer.
0 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 15 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 ~uch as:
20 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 corneaimmediately following photoablative refractive keratectomy. As a drop, ointment or 2s 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 comeal response may be modified by the pre-treatment with interferon o~ drops before PRX. It may also be modified by pre-treatment with steroid drops.
The interferon-a may be prepared from natural sources or may be prepared by 30 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-ol-2b to prevent corneal scarring after photoablative refractive keratectomy is administered topically to the cornea which has 3~ 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.
WO 93/06856 2 ~ 2 0 9 ~ ~ PCr/AU92/00541 Example 1 Preparation of interferon a-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 f~llows: ;
a-2b interferon solution Dibasic sodium phosphate, anhydrous, USP
Monosodium phosphate, monohydrate, USP
Glycine, ph. eur. ;
0 Human albumin solution, ph. eur.
Water for injection, ph. eur.
The drops base is hypromellose or polyvinyl alcohol for dilution to lo6 IU/ml,.
Example 2 The composition of this invention is applied to the cornea immediately followingls 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-a-2b drops before PRK. It may also be modified by pre-treatment with steroid dr~s. - ~
20 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 modifica'dons obvious to those sldlled in the art can be made thereto without departing 25 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.
,: ~ ....
The dosage range of interferon-o~ may be between about 50,000 and 50 x 106 IU
and may be between about I x 106 to 20 x lo6 lU/mL. Preferably the dosage is between about lx106 and about 10X106 IU/mL. The interferon-o~ may be administered in 50 ~L
drops, four times a day for six weeks; or preferably two times a day for one week.
Interferon-o~ may also be administered two times a day for three days or one drop hourly 5 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-a is given by intravitreal injection within the range of 50,000 to 5.0 x 106 IU/0.lmL.
The compositions of this invention may also contain a slow release polymer.
0 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 15 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 ~uch as:
20 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 corneaimmediately following photoablative refractive keratectomy. As a drop, ointment or 2s 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 comeal response may be modified by the pre-treatment with interferon o~ drops before PRX. It may also be modified by pre-treatment with steroid drops.
The interferon-a may be prepared from natural sources or may be prepared by 30 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-ol-2b to prevent corneal scarring after photoablative refractive keratectomy is administered topically to the cornea which has 3~ 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.
WO 93/06856 2 ~ 2 0 9 ~ ~ PCr/AU92/00541 Example 1 Preparation of interferon a-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 f~llows: ;
a-2b interferon solution Dibasic sodium phosphate, anhydrous, USP
Monosodium phosphate, monohydrate, USP
Glycine, ph. eur. ;
0 Human albumin solution, ph. eur.
Water for injection, ph. eur.
The drops base is hypromellose or polyvinyl alcohol for dilution to lo6 IU/ml,.
Example 2 The composition of this invention is applied to the cornea immediately followingls 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-a-2b drops before PRK. It may also be modified by pre-treatment with steroid dr~s. - ~
20 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 modifica'dons obvious to those sldlled in the art can be made thereto without departing 25 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 (22)
1. Use of interferon-.alpha. for treating corneal scarring, for inhibiting opacification of the posterior capsule after extracapsular cataract surgery, for inhibiting wound fibrosis 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-.alpha. 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 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-.alpha. is interferon-.alpha.-2A.
6. Use according to any one of claims 1 to 4 wherein interferon-.alpha. is interferon-.alpha.-2B.
7. Use according to any one of claims 1 to 4 wherein interferon-a is interferon-.alpha.-2C.
8. A process for preparing a composition of interferon-.alpha. comprising formulating interferon-.alpha. 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 (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 interferon-.alpha. or a pharmaceutical composition for the treatment of corneal scarring in a patient comprising interferon-.alpha. together with a pharmaceutically acceptable carrier, diluent and/or excipient.
13. A method for inhibiting opacification of the posterior capsule after extracapsular cataraci surgery, in a patient requiring such treatment, comprising administering to the lens capsule of said patient an effective amount of interferon-.alpha. or a pharmaceutical composition for this method comprising interferon-.alpha. 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-.alpha. or a pharmaceutical composition for this method comprising interferon-.alpha. 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-.alpha. 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-.alpha.
may be administered in about 50µL drops four times a day for six weeks.
may be administered in about 50µL drops four times a day for six weeks.
19. The method according to claim 18 wherein the interferon-.alpha. 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-.alpha.
is administered as one drop hourly for three days.
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-.alpha. or a pharmaceutical composition for this method comprising interferon-.alpha. together with a pharmaceutically acceptable carrier, diluent and/or excipient.
22. The method according to claim 21 wherein the interferon-.alpha. is given by intravitreal injection within the range of about 50,000 to 5.0 x 106 IU/0.lmL.
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 |
|---|---|
| CA2120950A1 true CA2120950A1 (en) | 1993-04-15 |
Family
ID=25644122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002120950A Abandoned CA2120950A1 (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) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2190510A1 (en) * | 1995-03-17 | 1996-09-26 | Saburo Sone | Corneal angiogenesis inhibitor |
| WO1997018831A1 (en) * | 1995-11-17 | 1997-05-29 | Toray Industries, Inc. | Endothelial cell protective |
| CA2243161A1 (en) * | 1996-11-22 | 1998-05-28 | Toray Industries, Inc. | Use of interferon-beta to treat retinal edema |
| AU5805998A (en) * | 1997-01-02 | 1998-07-31 | 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 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3262575D1 (en) * | 1981-12-23 | 1985-04-18 | Schering Corp | Stabilised interferon formulations and their preparation |
| DE3603444A1 (en) * | 1986-02-05 | 1987-08-06 | Thomae Gmbh Dr K | PHARMACEUTICAL PREPARATIONS FOR STABILIZING INTERFERON ALPHA |
| DE3628468A1 (en) * | 1986-08-21 | 1988-03-03 | Thomae Gmbh Dr K | NEW APPLICATION FORM (ALPHA) INTERFERONE |
| JPS6391331A (en) * | 1986-10-03 | 1988-04-22 | Senjiyu Seiyaku Kk | Ophthalmic aqueous composition |
| ZA878295B (en) * | 1986-11-06 | 1988-05-03 | Amarillo Cell Culture Co. Inc. | Treatment of immuno-resistant disease |
| AU2855189A (en) * | 1988-01-25 | 1989-07-27 | Baker Cummins Dermatologicals, Inc. | Method of treating fibrotic disorders |
-
1992
- 1992-10-12 EP EP92921557A patent/EP0607275A4/en not_active Withdrawn
- 1992-10-12 JP JP5506481A patent/JPH07501320A/en active Pending
- 1992-10-12 CA CA002120950A patent/CA2120950A1/en not_active Abandoned
- 1992-10-12 WO PCT/AU1992/000541 patent/WO1993006856A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0607275A1 (en) | 1994-07-27 |
| JPH07501320A (en) | 1995-02-09 |
| WO1993006856A1 (en) | 1993-04-15 |
| 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 | |
| Miller et al. | Regression of experimental iris neovascularization with systemic alpha-interferon | |
| EP1247532B1 (en) | Composition promoting lacrimal secretion | |
| US4740498A (en) | Fibronectin preparations | |
| KR20160147023A (en) | Compounds for treating ophthalmic diseases and disorders | |
| WO2002058730A2 (en) | Compositions for treatment of ocular neovascularization | |
| JPH10158188A (en) | Composition for treating cornea | |
| US20080176953A1 (en) | Methods and compositions for treatment of ocular neovascularization and neural injury | |
| Reim et al. | Surgical procedures in the treatment of most severe eye burns: revival of the artificial epithelium | |
| EP0434625B1 (en) | IGF-I for treating adverse effect of steroid therapy | |
| CA2120950A1 (en) | Treating ophthalmic fibrosis using interferon-alpha | |
| US5411940A (en) | Use of TGF-β3 to reduce the formation of scar tissue in response to corneal trauma | |
| Gelender | Bacterial endophthalmitis following cutting of sutures after cataract surgery | |
| WO2018066963A1 (en) | Pharmaceutical composition for treating corneal injury containing 8-oxo-deoxyguanosine or pharmaceutically acceptable salt thereof as active ingredient | |
| US5863530A (en) | Treating ophthalmic fibrosis using interferon-α | |
| US9011845B2 (en) | Methods for treatment of inflammatory and infectious viral diseases | |
| Ohashi | Treatment of herpetic keratitis with acyclovir: benefits and problems | |
| JPH06271478A (en) | Agent for treating dry eye | |
| AU669132B2 (en) | Treating ophthalmic fibrosis using interferon-alpha | |
| AU7846794A (en) | Compositions containing growth factors and antimetabolites | |
| EP0080032A2 (en) | Pharmaceutical preparation for treating herpetic lesions | |
| KR20170021745A (en) | 4 pharmaceutical composition for preventing or treating corneal wound comprising thymosine 4 and citric acid | |
| US5948403A (en) | Corneal angiogenesis inhibitor | |
| US8877183B2 (en) | Methods for treatment of ocular diseases | |
| MXPA04008776A (en) | Agents for corneal or intrastromal administration to treat or prevent disorders of the eye. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |