CN1549718A - Use of compounds for treating conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries - Google Patents
Use of compounds for treating conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries Download PDFInfo
- Publication number
- CN1549718A CN1549718A CNA028168682A CN02816868A CN1549718A CN 1549718 A CN1549718 A CN 1549718A CN A028168682 A CNA028168682 A CN A028168682A CN 02816868 A CN02816868 A CN 02816868A CN 1549718 A CN1549718 A CN 1549718A
- Authority
- CN
- China
- Prior art keywords
- people
- chemical compound
- corneal nerve
- corneal
- ait
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
-
- 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
- A61K31/075—Ethers or acetals
- A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- 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
- A61P27/04—Artificial tears; Irrigation solutions
Abstract
The present invention provides methods for the treatment of conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries or trauma.
Description
Background technology
1.
Technical field
The present invention relates to promote the chemical compound of neuron regeneration or axon growth to be used for the treatment of by laser in-situ keratomileusis (Laser In Situ Keratomileusis (LASIK)) or the wherein application of other postoperative corneal nerve damage of being damaged of corneal nerve situation about being caused.
2.
The description of related art
The patient usually experiences the sensitivity reduction and the slight xerophthalmia to moderate of cornea behind lasik surgery.For Most patients, this is a kind of acute problems that only continues several days.But, for a considerable amount of patients, sustainable some months of these problems or longer time (Yu 2000).This iatrogenic variation is likely because the intra-operative corneal nerve is cut off the (Wilson2001 that is caused; Ambrosio ﹠amp; Wilson 2001).The method of the xerophthalmia that treatment operation at present causes comprises alleviation such as the frequent local artificial tears of use such as the Tears Naturale or the Bion Tears of symptom, or other artificial wetting agent.But these treatments have reduced uncomfortable can not treat basic pathological changes.Known to the inventor, corneal sensitivity reduces does not at present have acceptable treatment.
Neurotrophic factor is the peptide molecule that stimulates or keep neuronal tissue's growth.Neurotrophic factor is essential from the transhipment of brain neurad unit cell space for the survival of most of ophthalmic nerves.Neurotrophic factor lacks can induce neuron programmed cell death people such as (, 1993) Raff.
The neurotrophin of peptide class (NT) section comprises nerve growth factor (NGF), Brain Derived Neurotrophic Factor (BDNF), NT-3, NT-4/5 and NT-6.They can work by combining as TrkA, TrkB, TrkC and p75NTR with neurotrophin receptor (NT-receptor).The Trk receptor is a tyrosine kinase.TrkA is selective to NGF, and TrkB is selective to BDNF and NT-4/5, and TrkC is selective to NT-3.After combination, NT-receptor complex by internalization and by axonal transport to cell space.The experience inductive phosphorylation of part of these receptors and dimerizations, and activate the protein mediated signal transduction incident of the Ras of a succession of first many critical functions that affect the nerves (people such as Lewin, 1997; People such as Segal, 1996; People such as Ebadi, 1997; People such as Kaplan, 1997).Therefore, these receptors in regulate forming neuronic survival and differentiation aspect play an important role and help and keeping neuronic structure in life.
For example, in ocular tissue, in amphiblestroid ganglionic cell (RGC), dopaminergic amacrine cell and optic nerve, all observed the mRNA of TrkA and TrkB.Confirmed that during neuron forms their expression is high degree of controlled (people such as Jelsma, 1993; People such as Rickman, 1995; People such as Ugolini, 1995; People such as Cellerino, 1997).Confirmed that TrkB receptor-selective ligands BDNF and NT-4/5 are effective to protection RGC.Many researchs show, these NT have not only improved survival and the axon growth of RGC in the culture, but also significantly reduced the damage that axon cuts off optic nerve and RGC in the inductive body of institute, and the growth of the branch that has stimulated aixs cylinder from the RGC that regenerates (people such as Anderson, 1974; People such as Quigley, 1976; People such as Mansour-Robaey, 1994; People such as Meyer-Franke, 1995; With people such as Cui, 1994).For example, when carrying out administration during first five days after damage, intravitreal injection 5 μ g BDNF have prevented optic nerve death (the Mansour Robaey 1994 of axon microsurgery separately; People such as Gao, 1997).
Ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) are other neurotrophic factors of supporting neuronal survival.They are structurally uncorrelated with neurotrophin.Confirmed that also they can prevent to damage inductive neuron and aixs cylinder death (people such as Mey, 1993; People such as Weibel, 1995).
In normal people and rat cornea, find to exist neurotrophic factor such as NGF people 2000 such as () Lambiase.The epithelial cell of people and rat cornea produces, storage and discharge NGF and express TrkA receptor people 1998 such as (, people such as Lambiase 2000) Lambiase.These trophic factors obviously play an important role in the biology of cornea.In the mice cornea that TrkA knocks out, the number of nerve trunk, branch and thin teleneuron sharply descends.These mices are to machinery, heat and the Blinking reflex of chemical destructive stimulus also significantly descend people such as (, 1998) De Castro.
Therefore, neurotrophic factor is very important for the health of cornea and normal function.But these trophic factors are peptide molecules, and therefore, it is owing to being difficult to be developed to medicine in the bioavailability problem that usually exists aspect the drug administration of peptide.Therefore, need to stimulate the neurotrophic activity in the impaired retinal tissue and do not have a non-peptide molecule of the bioavailability problem of natural peptide matters.
General introduction of the present invention
The present invention has overcome these defectives and other shortcoming of the prior art by compositions and the method that is provided for treating situation about being caused by the corneal nerve damage.Said composition comprises the chemical compound that one or more can promote neuron regeneration or axon growth in pharmaceutically useful carrier.
Here used " can promote the chemical compound of neuron regeneration or axon growth " refers to those generation or active chemical compounds that can increase neurotrophic factor in ocular tissue, especially cornea on the spot.Here used " neurotrophic factor " refers to NGF, BDNF, NT-3, NT-4/5, NT-6, CNTF, bFGF and maybe can prevent, treat or improve the corneal nerve pathological changes or promote other trophic factors that impaired corneal nerve unit regrows.The example of neurotrophic factor stimulus object comprises: AIT-082 (neotrofin), idebenone, CB-1093, NS521 ((1-(1-butyl)-4-(2-oxo-1-Benzimidazolinone) piperidines), SS-701 and KT-711 (all explanations below), ONO-2506 and Celenbuterol.The most preferred neurotrophin stimulus object of the present invention is AIT-082 (neotrofin).Above-mentioned molecule can obtain maybe can synthesize with the method for well known to a person skilled in the art by commercial sources.
Method of the present invention comprise to human patients use one or more chemical compounds that can promote neuron regeneration or axon growth for example the neurotrophic factor stimulus object come to since the situation that the corneal nerve damage that operation causes is caused treat.
Method of the present invention particularly relates to uses compounds for treating xerophthalmia that promotes neuron regeneration or axon growth and other disease such as the corneal sensitivity that is caused by the corneal nerve damage to descend.
According to well known to a person skilled in the art preparation technique, the present invention promotes the chemical compound of neuron regeneration or axon growth can be included in various types of pharmaceutical compositions.Generally speaking, the chemical compound of this promotion neuron regeneration or axon growth can be made the solution or the suspension of topical ophthalmic usefulness or eye drops, perhaps can make the tablet, capsule or the solution that are used for whole body administration (for example oral or intravenous administration).Chemical compound of the present invention preferably is prepared to solution or the suspension that topical ophthalmic is used.
Detailed description of the present invention
LASIK, and other operation of correcting defects of vision makes many people that wear correcting spectacle lens can not re-use correcting spectacle lens.This is favourable from many aspects.For some occupations as be engaged in for the people of art, science and building operation, because the essential contact of its work dust, pigment and chemicals, so correcting spectacle lens may be a kind of thing of disliking of making us feeling.But behind lasik surgery, the patient corneal sensitivity often occurs and descends and slight xerophthalmia to moderate.For Most patients, this is a kind of acute problems that only continues several days.But for a considerable amount of patients, this problem may continue some months or longer time (Yu 2000).This problem be likely since the intra-operative corneal nerve impaired cause (Wilson 2001; Ambrosio ﹠amp; Wilson 2001).The present inventor has been found that at used after operation and promotes axon growth or stimulate the chemical compound of cut or impaired neuranagenesis that impaired corneal nerve is treated persistent period that can shorten xerophthalmia or the sickness rate that reduces xerophthalmia.Such treatment can also alleviate by LASIK or wherein other corneal sensitivity of being caused of operation of suffering damage of corneal nerve descend.
The present invention relates to promote the application that the chemical compound of cut neuranagenesis and/or axon growth is used for the treatment of xerophthalmia and is descended by the caused corneal sensitivity of operation on cornea.Promote cut neuron regeneration or promote the chemical compound of axon growth to realize the function that it promotes cut neuron regeneration or promotes axon growth by the generation of the trophic factors that excites nerve or by the activity that increases neurotrophic factor.The used chemical compound of the present invention can also promote to be cut off neural regeneration and/or axon growth by directly acting on impaired nerve.
Some neurotrophic factor stimulus object in scientific and technical literature, have been reported, for example AIT-082 (Graul ﹠amp; Castaner 1997), idebenone (people such as Nabeshima, 1994), ONO-2506 (people such as Matsui, 1998), NS521 (people such as Gronborg, 1998), CB-1093 (people such as Aimone, 1998) and Celenbuterol (people such as Culmsee, 1998).But not open in the prior art or hint is treated lasik surgery or other postoperative xerophthalmia or other iatrogenic injury with the neurotrophic factor stimulus object.
Owing to be easy to administration, so the topical ophthalmic of preferred neuron regeneration or axon growth stimulus compound.Topical ophthalmic can be solution or suspension.Generally speaking, topical formulations comprises active neurotrophin factor stimulus object and inert excipient.
Compositions of the present invention can be damaged at corneal nerve, as being carried out eye drops after LASIK or other operation infringement.The compositions that is used for eye drops generally is intraocular injection compositions or surgery washing solution.The intraocular injection compositions generally is made of aqueous solution, the equilibrated as discussed below salt rinse solution of example.
When behind operation technique, neuron regeneration or axon growth being promoted that chemical compound carries out administration, for example, most preferably use equilibrated salt rinse solution as carrier by behind the eyeball or periocular injections and intraocular irrigation or injection when carrying out administration.The aseptic ophthalmic rinse solution of aseptic rinse solution of BSS and BSS Plus (Alcon Laboratories, Inc., Fort Worth, Texas USA) is the example that the physiology goes up equilibrated ophthalmic rinse solution.A kind of solution in back is to be described in 4,550,022 the United States Patent (USP) in the patent No., and its full content here is introduced into as a reference.Be known to those skilled in the art and in many publications, all be described with periocular injections behind the eyeball, for example
Ophthalmic Surgery:Principles of Practice (1990)Preferred route of administration is the eyes topicals.Therefore, can be used for the above-claimed cpd that contains pharmacy effective dose of local ophthalmic administration or the solution or the suspension of its active analogue thereof by well known to a person skilled in the art the method preparation.
Generally speaking, the dosage that is used for above-mentioned purpose can change, but should be the effective dose that prevents, alleviates or improve xerophthalmia or reduce with the relevant corneal sensitivity of performing the operation.Here used " pharmacy effective dose " refers to the amount that can prevent, alleviate or improve the neurotrophin factor stimulus object that xerophthalmia or the corneal sensitivity relevant with operation or wound reduce.This neurotrophic factor stimulus object generally is contained in topical formulations or pharmaceutically suitable carrier considered here with about 0.001 amount to about 10.0% weight/volume (%w/v).Preferred concentration is about 0.1 to about 5.0%w/v.Topical formulations general every day, it can be decided by the clinicist to ophthalmic administration one to six time.The compositions of whole body administration generally comprises the neurotrophic factor stimulus object of about 1-1000mg, and can use 1-4 time every day, and it can be decided by the clinician.
That terminology used here " pharmaceutically suitable carrier " refers to is safe, can be any preparation that required route of administration is transmitted at least a neurotrophic factor stimulus object of effective dose aptly.
Compositions of the present invention can comprise other pharmacy activity component or can with the administration simultaneously of other medicines compositions.Specifically, when in order to prevent, to treat or improve situation about being caused and when mammal treated by intra-operative corneal nerve damage, compositions of the present invention can comprise other active component or can with other material or compositions simultaneously or administration in succession.The example of other material comprises: artificial tears, artificial Wetting Solution or other well known to a person skilled in the art suitable material.
Embodiment
The following examples have proved the protection effectiveness of neurotrophic factor stimulus object (propentofylline) to ocular tissue's cell injury.
Embodiment 1
This chemical compound can the whole body administration or to eyes topical (for example, in topical, the eye-chamber administration or by implanting administration).This chemical compound preferably is blended into the topical ophthalmic preparation that is used for ophthalmic administration.This chemical compound can with can the eye usefulness antiseptic, surfactant, viscosifier, penetration enhancer, buffer agent, sodium chloride and hydration in order to form a kind of aseptic aqueous ophthalmic suspension or solution.Ophthalmic solution formulations can be by being prepared compound dissolution in physiologically acceptable isotonic water buffer.In addition, this ophthalmic solution can also comprise can the eye usefulness surfactant to help the dissolving of chemical compound.In addition, this ophthalmic solution can also comprise the material that is used for increasing viscosity such as hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, methylcellulose, polyvinylpyrrolidone or the like to improve the reservation of said preparation at conjunctival sac.Can also use gellant, it comprises gellan gum and xanthan gum without limitation.In order to prepare aseptic ophthalmic ointment, active component and antiseptic can be mixed wherein said suitable substrate such as mineral oil, liquid lanolin or white vaseline in suitable substrate.Aseptic eye-gel preparation can be prepared by active component being suspended in the prepared hydrophilic matrix of combination by for example carbopol-940 grade according to the disclosed prescription that is used for similar ophthalmic preparation; Can be to wherein sneaking into antiseptic and tonicity agents.
It is about 5 to 8 local ophthalmic suspension or solution that this chemical compound preferably is made into pH.The amount that is contained in this chemical compound in these preparations is generally 0.001% to 5% weight, but is preferably 0.05% to 2% weight.Therefore, for topical, consider according to clinician's routine, every day 1 to 4 time with 1 to 2 these agent delivery to ocular surface.
According to description of the invention, do not need to carry out too much experiment and just can prepare and implement all compositionss and/or method disclosed and that require here.Though the compositions and methods of the invention are described with embodiment preferred, but obviously can change the step of said composition and/or method and method described here or the order of step to those skilled in the art, it can not break away from notion of the present invention, purport and scope.Specifically, obviously can substitute material as described herein with some material that chemistry and structure all are correlated with and obtain similar result.All such conspicuous to those skilled in the art replacements and change still are included in by in the defined purport of the present invention of appended claim, scope and the notion.
Reference material
Provide example operation or other detailed content below with reference to data for content described here, therefore be incorporated herein by reference especially.
United States Patent (USP)
4,550,022
Books
Ophthalmic Surgery:Principles of Practice, editor G.L.Spaeth, W.B.Sanders Co., Philadelphia, PA, U.S.A., 85-87 page or leaf (1990)
Other publication
People such as Aimone, 1 α, 25 (OH)
2D
3Analog CB-1093 induces nerve growth factor in inhuman Primate brain, Society For Neurosci., summary, 24:292, (1998).
Ambrosio?&?Wilson，J.Refractive?Surgery?17：350-380(2001)。
People such as Anderson, intraocular pressure is to the influence of axoplasmic transport fast in the monkey optic nerve, Invest.Ophthalmol, 13:771-783 (1974).
People such as Beck, Brain Derived Neurotrophic Factor is to the protective effect of ischemic cell injury in the rat hippocampus, J.Cereb.Blood Flow Metab., 14:689-692 (1994).
People such as Cellerino, Brain Derived Neurotrophic Factor/neurotrophin-4 receptor TrkB is positioned in vertebrates retinal ganglial cells and the dopaminergic amacrine cell, J.Camp.Neurol., 386:149-160 (1997).
People such as Cui, Nt-4/5 have reduced the naturally occurring retinal ganglial cells death of neonate rat, Neuroreport, 5:1882-1884 (1994).
People such as Culmsee, the NGF antisense oligonucleotide has been blocked the protective effect of Celenbuterol to cerebral ischaemia in inductive external exitotoxicity of glutamate, Glu and the body, Society For Nneurosci., summary, 24:295 (1998).
People such as De Castro, the corneal nerve of TrkA knock-out mice distributes and to the sensitivity of destructive stimulus, Eup.J.Neurosci., 10:146-152 (1998).
People such as Ebadi, neurotrophin and receptor thereof in nerve injury and reparation, Neurochem Int., 30:347-374 (1997).
People such as Gao, the mRNA of the rising of Brain Derived Neurotrophic Factor expresses in the ganglion cell layer of retina behind optic nerve injury, Invest.Ophthalmol.Vis.Sci., 38:1840-1847 (1997).
Graul?&?Castaner，AIT-082，Drugs?of?The?Future，22：945-947(1997)。
People such as Gronborg, the neuroprotective of new compound Ns521, Society ForNeurosci., summary, 24:1551 (1998).
People such as Jelsma, it is multi-form that the neurotrophin receptor TrkBmRNA in rat retina and optic nerve dominates, J.Neurobiol., 24:1207-1214 (1993).
People such as Kaplan, the signal transduction that the neurotrophin receptor carries out, Curr.Opin.Cellbiol., 9:213-221 (1997).
People such as Kirsch, the sign of the multiple local function of ciliary neurotrophic factor in the retinal development (CNTF): CNTF and receptor expression thereof and to the interaction in vitro of target cell, J.Neurochem., 68:979-990 (1997).
People such as Lambiase, healthy individual and the expression of ocular surface nerve growth factor during the inflammatory diseases occurs, Invest.Ophthalmol.Vis.Sci., 39:1272-1275 (1998).
People such as Lambiase, the facilitation of nerve growth factor corneal healing: structure, biochemistry and the analysis of molecules of rat and people's cornea, Invest.Ophthalmol.Vis.Sci., 41:1063-1069 (2000).
People such as Lewin, the physiology of neurotrophin, Ann.Rev.Neurosci, 19:289-317 (1997).
People such as Lindholm, Brain Derived Neurotrophic Factor is the neuronic existence key element of rat cerebellum granule of being cultivated and protects it not to be subjected to inductive neurovirulent influence of glutamate, Glu, Eur.J.Neurosci., 5:1455-1464 (1993).
People such as Mansour-Robaey, the administration of ocular damage and Brain Derived Neurotrophic Factor is to the survival of the retinal ganglial cells of axon cut-out and the influence of growth, Proc.Natl.Acad.Sci.USA, 91:1632-1636 (1994).
People such as Matsui are at the protective effect of the permanent closed 1 week back ONO-2506 of intraluminal middle cerebral artery occlusion in rats to neurological deficit and cerebral infarction volume, Society For Neurosci., summary, 24:254 (1998).
People such as Mey, the support effect that the retinal ganglial cells that the intravitreal injection neurotrophic factor cuts off the adult rat axon is in vivo survived, Brain Res., 602:304-317 (1993).
People such as Meyer-Franke, the feature description of the developmental retinal ganglial cells survival that promotion is cultivated and the signal interaction of growth, Neuron, 15:805-819 (1995).
People such as Nabeshima, the oral administration of the synthetic stimulus object of NGF is to the restitution of the reduction of senile rat brain NGF content and substrate-preceding cerebral lesion rat cognitive function disorder, Gerontology, 40 (supplement 2): 46-56 (1994).
People such as Quigley, the acute intraocular pressure of Primates optic nerve raises to aixs cylinder transfering dynamics and localized blocking-up, Invest.Ophthalmol., 15:606-616 (1976).
People such as Raff, the control of programmed cell death and cell survival: derive from neural lesson, Science, 262:695-700 (1993).
People such as Rickman, the proto-oncogene-expression of Trk-receptor in developmental rat retina, Vis.Neurosci., 12:215-222 (1995).
People such as Segal are by signal transduction path in the activated cell of neurotrophic factor, Ann.Rev.Neurosci., 19:463-489 (1996).
People such as Ugolini, TrkA, TrkB and p75mRNA are expressed in the developmental regulation in the rat retina, Brain Res, 704:121-124 (1995).
People such as Unoki, Brain Derived Neurotrophic Factor, ciliary neurotrophic factor and basic fibroblast growth factor are to preventing the protective effect of rat retina ischemic injury, Invest.Ophthalmol.Vis.Sci., 35:907-915 (1994).
People such as Weibel, Brain Derived Neurotrophic Factor (BDNF) can be prevented the aixs cylinder dieback of the young rat optic nerve that caused by damage, Brain Res., 679:249-254 (1995).
Wilson，Ophthalmology?108：1082-1087(2001)。
Yu, Symposium on Cataract, IOL and Refractory Surgery, summary 263 (2000).
Claims (18)
1. the method for the xerophthalmia that caused by the corneal nerve damage of a treatment, described method comprises the compound compositions that comprises at least a promotion neuron regeneration or axon growth to patient's administering therapeutic effective dose of the described treatment of needs.
2. the method for claim 1, wherein said corneal nerve damage is caused by operation.
3. method as claimed in claim 2, wherein said operation is a lasik surgery.
4. the method for claim 1, wherein said chemical compound can be selected from propentofylline, AIT-082 (neotrofin), idebenone, ONO-2506, CB-1093, NS521 (1-(1-butyl)-4-(2-oxo-1-Benzimidazolinone) piperidines), eliprodil, SR57746A (xaliproden hydrochlorate) or its pharmaceutically useful analog.
5. method as claimed in claim 4, wherein said chemical compound is AIT-082.
6. method as claimed in claim 4, wherein said chemical compound is an eliprodil.
7. the method that descends of the corneal sensitivity that caused by the corneal nerve damage of a treatment, described method comprises at least a compound compositions that promotes neuron regeneration or axon growth that comprises to patient's administering therapeutic effective dose of the described treatment of needs.
8. method as claimed in claim 7, wherein said corneal nerve damage is caused by operation.
9. method as claimed in claim 8, wherein said operation is a lasik surgery.
10. method as claimed in claim 7, wherein said chemical compound can be selected from propentofylline, AIT-082 (neotrofin), idebenone, ONO-2506, CB-1093, NS521 (1-(1-butyl)-4-(2-oxo-1-Benzimidazolinone) piperidines), eliprodil, SR57746A (xaliproden hydrochlorate) or its pharmaceutically useful analog.
11. method as claimed in claim 10, wherein said chemical compound is AIT-082.
12. method as claimed in claim 10, wherein said chemical compound is an eliprodil.
13. a method for the treatment of the corneal nerve damage, described method comprise the compound compositions that promotes neuron regeneration or axon growth that comprises to patient's administering therapeutic effective dose of the described treatment of needs.
14. method as claimed in claim 13, wherein said corneal nerve damage is caused by operation.
15. method as claimed in claim 14, wherein said operation is a lasik surgery.
16. method as claimed in claim 13, wherein said chemical compound can be selected from propentofylline, AIT-082 (neotrofin), idebenone, ONO-2506, CB-1093, NS521 (1-(1-butyl)-4-(2-oxo-1-Benzimidazolinone) piperidines), eliprodil, SR57746A (xaliproden hydrochlorate) or its pharmaceutically useful analog.
17. method as claimed in claim 16, wherein said chemical compound is AIT-082.
18. method as claimed in claim 16, wherein said chemical compound is an eliprodil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31565201P | 2001-08-29 | 2001-08-29 | |
| US60/315,652 | 2001-08-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1549718A true CN1549718A (en) | 2004-11-24 |
Family
ID=23225436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA028168682A Pending CN1549718A (en) | 2001-08-29 | 2002-07-23 | Use of compounds for treating conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1420791A4 (en) |
| JP (1) | JP2005502678A (en) |
| CN (1) | CN1549718A (en) |
| AR (1) | AR036194A1 (en) |
| BR (1) | BR0212151A (en) |
| CA (1) | CA2455896A1 (en) |
| MX (1) | MXPA04001255A (en) |
| PL (1) | PL368565A1 (en) |
| WO (1) | WO2003020281A1 (en) |
| ZA (1) | ZA200400837B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE525111T1 (en) * | 2003-04-18 | 2011-10-15 | Senju Pharma Co | 2-CHLORO-6,7-DIMETHOXY-N-5 Ä5-(1)H-INDAZOLYLUQUINAZOLINE-4-AMINE, N-(1-BENZYL-4-PIPERIDINYL)-1H-INDAZOLE-5-AMINE DIHYDROCHLORIDE, 4-Ä2 -(2,3,4,5,6- |
| ES2234428B1 (en) * | 2003-12-09 | 2006-11-01 | Universidad Miguel Hernandez | COMPOUNDS FOR THE TREATMENT OF THE DROUGHT OF THE OCULAR SURFACE CAUSED BY THE PHOTO-REFRECTIVE SURGERY. |
| CA2563882A1 (en) * | 2004-04-23 | 2005-11-03 | Senju Pharmaceutical Co., Ltd. | Corneal neuritogenesis promoter containing pacap and its derivative |
| CN1795196B (en) | 2004-06-03 | 2013-07-24 | 千寿制药株式会社 | Use of amide in preparing compound agent for repairing corneal sensitivity |
| JPWO2006098292A1 (en) | 2005-03-15 | 2008-08-21 | 小野薬品工業株式会社 | Eye disease treatment |
| CN113350326B (en) * | 2021-07-28 | 2023-03-17 | 爱尔眼科医院集团股份有限公司 | Application of compound LM22B-10 in preparation of corneal epithelium and nerve injury treatment drugs |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5166317A (en) * | 1988-10-31 | 1992-11-24 | Houston Biotechnology Incorporated | Neurotrophic factor |
| FR2672213B1 (en) * | 1991-02-05 | 1995-03-10 | Sanofi Sa | USE OF 4- (3-TRIFLUOROMETHYLPHENYL) -1,2,3,6-TETRAHYDROPYRIDINIC DERIVATIVES AS SENSORS OF FREE RADICALS. |
| US5767079A (en) * | 1992-07-08 | 1998-06-16 | Celtrix Pharmaceuticals, Inc. | Method of treating ophthalmic disorders using TGF -β |
| US5604244A (en) * | 1995-06-07 | 1997-02-18 | Alcon Laboratories, Inc. | Intraocular irrigating solution containing a polyamine antagonist |
| TWI246421B (en) * | 1998-12-03 | 2006-01-01 | Alcon Mfg Ltd | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases |
| AU2001261360A1 (en) * | 2000-05-10 | 2001-11-20 | Alcon, Inc. | R-eliprodil for treating glaucoma |
-
2002
- 2002-07-23 MX MXPA04001255A patent/MXPA04001255A/en not_active Application Discontinuation
- 2002-07-23 JP JP2003524588A patent/JP2005502678A/en not_active Withdrawn
- 2002-07-23 CA CA002455896A patent/CA2455896A1/en not_active Abandoned
- 2002-07-23 CN CNA028168682A patent/CN1549718A/en active Pending
- 2002-07-23 BR BR0212151-4A patent/BR0212151A/en not_active Application Discontinuation
- 2002-07-23 WO PCT/US2002/023871 patent/WO2003020281A1/en not_active Application Discontinuation
- 2002-07-23 EP EP02756710A patent/EP1420791A4/en not_active Withdrawn
- 2002-07-23 PL PL02368565A patent/PL368565A1/en unknown
- 2002-07-30 AR ARP020102872A patent/AR036194A1/en unknown
-
2004
- 2004-02-02 ZA ZA200400837A patent/ZA200400837B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1420791A4 (en) | 2004-09-15 |
| PL368565A1 (en) | 2005-04-04 |
| ZA200400837B (en) | 2005-02-02 |
| MXPA04001255A (en) | 2004-05-27 |
| JP2005502678A (en) | 2005-01-27 |
| EP1420791A1 (en) | 2004-05-26 |
| BR0212151A (en) | 2004-08-24 |
| AR036194A1 (en) | 2004-08-18 |
| CA2455896A1 (en) | 2003-03-13 |
| WO2003020281A1 (en) | 2003-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5582535B2 (en) | Treatment or prevention of neurological or neuropsychiatric disorders by eye drops | |
| CN108135737A (en) | For treating pteryium composition and method | |
| CN109908140A (en) | The purposes of biotin treatment multiple sclerosis | |
| CN101048156A (en) | Inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases | |
| CN1549718A (en) | Use of compounds for treating conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries | |
| JP2016026229A (en) | Ophthalmic preparations based on bdnf (brain-derived neurotrophic factor) and their use | |
| CN1325308A (en) | Use of neurotrophic factor stimulators for treatment of ophthalmic neurodegenerative diseases | |
| CN1302810C (en) | Optic nerve protecting agents containing alpha1 receptor blocker as the active ingredient | |
| JP2014510115A (en) | Ophthalmic formulation based on PACAP (pituitary adenylate cyclase activating polypeptide) that restores normal visual function in early glaucoma | |
| CN1870989A (en) | Coumarin derivative for treatment of ophthalmic disorders | |
| US20040162315A1 (en) | Use of compounds for treating conditions resulting from injury to the corneal nerve after LASIK and other ocular surgeries or trauma | |
| RU2134107C1 (en) | Preparation "gistokhrom" for treatment of eye retina and cornea inflammatory sicknesses | |
| CN105935443A (en) | Pharmaceutical composition for treating diabetic cataract | |
| JP4268912B2 (en) | Drug sustained-release contact lens kit | |
| CN1838955A (en) | Flupirtine preparation for treating neurodegenerative disorders of the visual system and diabetes mellitus | |
| CN1049602C (en) | Compound injection for curing ischemic eye disease | |
| AT402691B (en) | USE OF GALANTHAMINE FOR PRODUCING MEDICINAL PRODUCTS FOR TREATING TRISOMY 21 OR RELATED TRISOMY SYNDROME | |
| RU2224519C2 (en) | Antioxidant and nervous cell growth-stimulating agent | |
| AU2002322700A1 (en) | Use of compounds for treating conditions resulting from injury to the corneal nerve after lasik and other ocular surgeries or trauma | |
| JP2004331502A (en) | Optical nerve cell protecting agent | |
| KR20190099495A (en) | Ophthalmic Formulations | |
| US6906077B1 (en) | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases | |
| EP1169026B1 (en) | Use of ap-1 activators to treat glaucoma and ocular hypertension | |
| KR20240050324A (en) | Myopia treatment method using vinpocetine | |
| MXPA01002895A (en) | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |