+

WO2000076454A2 - Compositions therapeutiques a usage ophtalmique et compositions therapeutiques destinees au traitement des lesions cerebrales centrales - Google Patents

Compositions therapeutiques a usage ophtalmique et compositions therapeutiques destinees au traitement des lesions cerebrales centrales Download PDF

Info

Publication number
WO2000076454A2
WO2000076454A2 PCT/JP2000/003830 JP0003830W WO0076454A2 WO 2000076454 A2 WO2000076454 A2 WO 2000076454A2 JP 0003830 W JP0003830 W JP 0003830W WO 0076454 A2 WO0076454 A2 WO 0076454A2
Authority
WO
WIPO (PCT)
Prior art keywords
ion
composition
treating
optic nerve
sodium
Prior art date
Application number
PCT/JP2000/003830
Other languages
English (en)
Japanese (ja)
Other versions
WO2000076454A3 (fr
Inventor
Shinseiro Okamoto
Kentaro Okamoto
Original Assignee
Advanced Medicine Research Institute
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Advanced Medicine Research Institute filed Critical Advanced Medicine Research Institute
Priority to AU51094/00A priority Critical patent/AU5109400A/en
Publication of WO2000076454A2 publication Critical patent/WO2000076454A2/fr
Publication of WO2000076454A3 publication Critical patent/WO2000076454A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • 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
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A61K38/063—Glutathione
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A61P27/12—Ophthalmic agents for cataracts

Definitions

  • the present invention relates to a composition for treating ophthalmology and a composition for treating central cerebral lesions, and more particularly, for treating optic nerve dysfunction such as glaucoma, treating a lesion of the optic nerve itself, treating retinal damage, treating cataract, and
  • the present invention relates to a composition for ophthalmic treatment such as treatment of corneal wounds, and a composition for treatment of central cerebral lesions by optic nerve axon transport.
  • Glaucoma is an optic nerve dysfunction caused by increased intraocular pressure, which causes the optic nerve to be compressed by the optic papilla, which is the entrance and exit of the eye, resulting in dysfunction.
  • An increase in intraocular pressure may trigger apoptosis of the optic nerve, causing optic nerve dysfunction.
  • glaucoma treatment has only reduced intraocular pressure with eye drops from Procker or oral administration of intraocular pressure-lowering drugs.
  • the vision loss or tunnel vision be lowered intraocular pressure continues to progress, therefore c that has been made can not be prevented even when administered vitamin B 12 and the blood flow improving agent, insufficient only lowers the intraocular pressure
  • drugs that maintain, improve, grow and regenerate the function of the optic nerve itself are needed. There is also a need for drugs that prevent apoptosis of the optic nerve.
  • optic nerve dysfunction due to optic canal fractures, intraorbital tumors, optic nerve compression due to arterial varices, intracranial disease, brain tumors, pituitary tumors, hemorrhage, and infarction can cause optic nerve damage.
  • a simple treatment method for these is desired.
  • Alzheimer's disease demyelinating neurological disease, autoimmune disease, cerebral hemorrhage, cerebral infarction, brain tumor, cerebral atrophy, brain trauma, aging, treatment of other intracranial lesions, Parkinson's disease , Multiple schizophrenia, amyotrophic lateral sclerosis, etc., and limbs caused by pronunciation disorders, olfactory disorders, movement disorders, sensory disorders, general paralysis, hemiplegia resulting from various brain lesions
  • An object of the present invention is to provide an ophthalmic composition that is useful for treating optic nerve dysfunction, particularly glaucoma, by preventing apoptosis and directly acting on the optic nerve.
  • An object of the present invention is to provide an ophthalmic composition useful for treating dysfunction, particularly glaucoma.
  • Another object of the present invention is to provide an ophthalmic composition capable of treating optic nerve dysfunction by a simple administration method without imposing an excessive burden on patients and doctors.
  • Another object of the present invention is to provide a composition for treating a cerebral center lesion which treats a cerebral center lesion by optic nerve axonal transport.
  • Yet another object of the present invention is to provide a composition for preventing or treating retinal degeneration.
  • the present invention is a.
  • composition for ophthalmic treatment and a composition for treatment of central cerebral lesions, comprising
  • FIG. 1 is a view showing the therapeutic effect of the composition of the present invention on recovery of pupil photoreactivity according to Test Example 1.
  • FIG. 2 is a diagram showing the therapeutic effect of the composition of the present invention on rabbit eyes with optic nerve damage according to Test Example 2.
  • FIG. 3 is a schematic diagram of a laser Doppler cataract measuring device and a measuring method used in Test Example 3.
  • FIG. 4 is a schematic diagram showing a fast component (A) and a slow component (B) of the autocorrelation function in the measurement of lens opacity.
  • FIG. 5 (a) is a diagram showing the cataract treatment effect of Test Example 3 of the composition of the present invention
  • FIG. 5 (b) is a diagram showing an example of standing.
  • FIG. 6 is a graph showing the therapeutic effect of the composition of the present invention on retinal lesions in Test Example 4.
  • FIG. 6 (a) shows normal ERG (retinal electrogram) immediately before the start of corneal suction.
  • FIG. 6 (b) shows the ERG immediately after the compression is released
  • FIG. 6 (c) shows the ERG one week after the end of the compression.
  • compositions of the present invention are sodium ion 50 to 25 OmM / L; potassium ion 2.5 to 8 mM / L; calcium ion 0.5 to 2 mM / L; magnesium ion 0.5 to 2 mM / L; 80 to 18 OmM / L; phosphate ion 1.5 to 4.5 mM / L; carbonate ion 15 to 35 mMA; glucose 0 to 7 mM / L; and oxyglutathiol 0.1 to 0.6 mL.
  • compositions of the present invention are sodium ion about 153 mM / L; potassium ion about 5.
  • compositions of the present invention can be from any pharmaceutically suitable compound source, such as sodium, potassium, calcium, magnesium chloride, phosphate, hydrogen phosphate, carbonate, and bicarbonate.
  • it is derived from sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium phosphate, sodium hydrogen phosphate, sodium hydrogen carbonate and sodium carbonate.
  • the most preferred composition of the present invention comprises about 122 mM / L sodium chloride, about 5.1 mM / L potassium chloride, about 1.1 mM / L shiridani calcium, about 1.0 mM / L magnesium chloride, phosphoric acid It contains about 3.OmM of sodium hydrogen, about 25m / L of sodium bicarbonate, glucose 0 to about 5. ImML, and about 0.3m / L of oxyglutathione.
  • compositions having compositions similar to the therapeutic compositions of the present invention for intraocular and extraocular perfusion and irrigation during ophthalmic surgery.
  • none of the prior art documents describes that such a composition can be used as a therapeutic agent, and there is no description suggesting that.
  • composition of the present invention may be any of an ophthalmic injection (subconjunctival injection, ophthalmic injection, intraocular injection), an ophthalmic external preparation (ophthalmic ophthalmic ophthalmic ointment), etc.
  • ophthalmic injection subconjunctival injection, ophthalmic injection, intraocular injection
  • ophthalmic external preparation ophthalmic ophthalmic ophthalmic ointment
  • a dosage form for topical administration to the eye is preferred. Ointments are preferred.
  • the optic nerve dysfunction in the present invention includes, for example, optic nerve dysfunction due to optic canal fracture or intraorbital tumor or optic nerve compression due to arteriovenous aneurysm; intracranial disease; brain tumor; pituitary tumor or hemorrhage ⁇ blood circulation disorder ⁇ optic nerve function due to infarction Disorders and glaucomatous optic nerve disease.
  • Glaucoma applied to the present invention includes low-tension glaucoma (normal-tension glaucoma; In this case, it can be said that the optic nerve itself is impaired. Apoptosis is also possible. ) And high-tension glaucoma (open-angle glaucoma or narrow-angle glaucoma (acute inflammatory glaucoma), congenital glaucoma, secondary glaucoma), etc., but the present invention is not limited to these. It is effective in all other types of optic nerve dysfunction, especially glaucoma.
  • the lesion of the optic nerve itself in the present invention includes, for example, retrobulbar optic neuritis and axial optic neuritis.
  • a retinal lesion in the present invention can include any condition involving damage or degeneration of photoreceptors or other retinal cells, for example, retinal detachment, macular disorder, photoretinopathy, diabetic retinopathy, toxic retinopathy, immaturity Retinopathy, viral retinopathy, ischemic retinopathy, peripheral vitreoretinopathy, hereditary retinal degeneration, retinitis pigmentosa, hypertensive retinopathy, chorioretinal atrophy, central retinal vein occlusion, Central retinochoroiditis, S Gol bottom bleeding.
  • the composition of the present invention for treating diabetic retinopathy it is clinically better to reduce the amount of glucose or to eliminate glucose.
  • the cataract in the present invention includes congenital cataract and late cataract, and senile cataract.
  • the therapeutic composition of the present invention acts on the optic nerve by local administration to the eye such as eye drops, is taken in, and is transferred into the skull by axon transport (active) of the optic nerve. Exhibits therapeutic effects.
  • treatment of various neurological diseases causing apoptosis such as Alzheimer, demyelinating neurological disease, autoimmune disease, cerebral hemorrhage, cerebral infarction, brain tumor, brain atrophy, brain trauma, aging, treatment of other intracranial lesions, Parkinson's disease, It is effective for multiple sclerosis, amyotrophic lateral sclerosis, etc.
  • composition of the present invention It is also effective in accelerating rehabilitation treatment and recovery of various functions, and can reduce bedridden elderly people. As a result, rehabilitation will be accelerated and will help prevent aging.
  • additives and bases known in the art are appropriately used.
  • other active ingredients for example, a neurotrophic factor and its derivative may be added to the composition of the present invention.
  • composition of the present invention is prepared as an eye drop and an ointment will be described below.
  • the eye drops and eye ointments of the present invention may optionally contain isotonic agents, bases, pH adjusters, thickeners, suspending agents, emulsifiers, preservatives, and other pharmaceutically acceptable additives. Can be added.
  • Examples of the aqueous base used in the present invention include sterilized purified water, solvents such as physiological saline, and purified water containing vitamin B12.
  • Examples of the non-aqueous base include cottonseed oil and soybean oil.
  • vegetable oils such as sesame oil, peanut oil, castor oil, olive oil, camellia oil, rapeseed oil and corn oil, and liquid paraffin.
  • the tonicity agent is not particularly limited as long as it is used in the field. In particular, boric acid, potassium nitrate, D-mannitol, glucose, and the like are preferable. 0.6 to 2.0 is acceptable.
  • the pH adjuster is not limited as long as it is used in this field, but boric acid, hydrochloric acid, acetic acid, borax, a buffer, and the like are particularly preferable.
  • the amount of the pH adjuster is the pH of the ophthalmic composition. Should be an amount that can be adjusted to 3.0 to 8.0.
  • the above-mentioned thickener is not limited as long as it is used in the relevant field.
  • the amount of use may be the consistency of dripping from an eye dropper bottle, but may be, for example, 0.001% to 10% (W / V).
  • the suspending agent is not limited as long as it is used in the art.
  • polysorbate 80 (trade name), polyoxyethylene castor oil, polyoxy-hardened castor oil, carboxymethyl cellulose, and the like can be used. It is preferable that the amount used is in the range of 0.001% to 10% (W / V).
  • the emulsifier is not limited as long as it is used in the field.Especially, egg yolk lecithin, polysorbate 80 and the like are preferable, and the amount of the emulsifier is 0.001% to 10% (W / V). Should be fine.
  • the preservative is not limited as long as it is used in the art, but in particular, preferably, salt fenzari benzalkonium, salt hazeride benzenitonium, chlorobutanol, phenylethyl alcohol, and paraoxybenzoate are preferred.
  • the used amount may be 0.001% to 10% (W / V).
  • the base of the ophthalmic ointment is not limited as long as it is used in the field, and particularly, vaseline, gelled hydrocarbon, polyethylene glycol, purified lanolin and the like are preferable.
  • Glaucoma is thought to occur because the optic nerve is compressed by the increase in intraocular pressure at the optic disc, which is the entrance and exit of the eye, and as a result, dysfunction occurs.
  • the path of the light response of the pupil is the eye-optic nerve (afferent) —central—parasympathetic nerve (efferent) —iris, and optic nerve damage due to glaucoma causes afferent dysfunction. Appears as a decline. Therefore, in this test, the light response of the pupil was measured using colored rabbits that increased intraocular pressure, caused optic nerve dysfunction, and reduced the light response of the pupil to stimulus light. The therapeutic effect of the ophthalmic composition of the present invention was confirmed.
  • the stimulus light source for the light response measurement is Neite Brite's scope (Neitz Brite
  • a + 14D convex lens was placed in front of the eye at a distance of 7 cm, and the inside of the eye was illuminated with the light that was once focused and diffused, and an open loop was formed to uniformly illuminate a wide area of the fundus .
  • optic nerve dysfunction due to increased intraocular pressure was determined, and the therapeutic effect of the ophthalmic composition of the present invention was determined.
  • aspiration was performed for 9 hours except that the aspiration was paused twice a day, in the morning and afternoon, when eating and drinking rabbits for 1 hour.
  • Attenuation of the light response to the stimulating light was scarcely observed by aspiration for 1 week and 2 weeks, but began to be observed from the 3rd week.c
  • the suction was stopped after one month of suction, and the progress of the light response was observed for one month and one week.
  • the ophthalmic composition of the present invention (Preparation Example 1) was instilled four to one times a day from one drop to several drops (the administered drug solution was absorbed from the cornea and moved into the aqueous humor, Some of them reach the optic disc from the croquettes, exert their effects on nerve fibers, some diffuse into the vitreous, reach the optic nerve, and some of the abnormal humor in the unusual rumen.
  • G unconventional route
  • the therapeutic effect (recovery degree) is measured by measuring the light response immediately after opening the suction, and using the pupil diameter at this time as a reference value, subtracting the value of the pupil diameter showing the light response recovered over time from the reference value. photoreactive variation was calculated as delta 7.
  • the therapeutic effect of the ophthalmic composition of the present invention appears in one week, and the visual nerve function gradually recovers with time.
  • V E P visual evoked potential
  • a ring-shaped sclerocorneal suction device I was created and attached to the left eye of colored rabbits and white rabbits, and intraocular pressure was increased with an air pump (non-noise S500, trade name, manufactured by Nippon Animal Pharmaceutical).
  • the sclera was aspirated from the periphery of the cornea in a ring shape so as to increase to 6 O mmHg.
  • the increase in intraocular pressure was confirmed using a simple jump tonometer (manufactured by Chiron).
  • Rabbits measured VEP after the end of the suction ring I by suction ring and the following morning.
  • the ophthalmic composition of the present invention was started to be instilled when the reduced potential was not recovered the next morning.
  • VEP was measured using a Neuropack 2 evoked potential tester (MEB-7102, trade name, manufactured by Nihon Kohden) by the following method (2-channel flash VEP method).
  • the extraction electrode (1) was punctured and fixed subcutaneously to the left side of the occipital region of the rabbit (channel 1, right eye stimulation potential) and right occipital region (channel 2, left eye stimulation potential), and the reference electrode (+) was fixed to the ear (right and left connection)
  • the ground electrode was fixed to the forehead.
  • the rabbits were dark-adapted and measured under the following measurement conditions.
  • VEP is a response that occurs in the visual cortex of the cerebral cortex when photostimulation is applied to retinal photoreceptors.Excitement generated in the retina is transmitted from the optic nerve via the optic nerve to another neuron in the lateral geniculate body.
  • the cerebral cortex leads to the visual cortex.
  • stimulus from one eye is transmitted to the left and right brains by optic nerve crossing, and the optic nerve of the rabbit is completely crossed, so that all excitation of the retina of the left eye is transmitted to the visual cortex of the right brain.
  • VEP was measured once or twice daily after the start of treatment with the composition of the present invention. The results are shown in FIG. Recovery of the optic nerve function over time of rabbit eyes VEP in which the composition of the present invention was instilled for 21 days was observed. Recovery of VEP was also observed in rabbit eyes in which the control solution was instilled, but it was very slight.
  • a confirmation test of the cataract treatment effect of the composition of the present invention was performed.
  • the opacity is measured by irradiating the lens with a diode laser (FP64 / 5AE manufactured by AUTEX), receiving the scattered light with a photomultiplier (H4730-1 manufactured by Hamamatsu Photonics), and creating an autocorrelator using a hardware window. (Correlator) was used to calculate the autocorrelation function, and the particle diameter was measured.
  • a laser Doppler cataract measurement device N0DEC V0-1000 (prototype) was used.
  • Fig. 3 shows a schematic diagram of this device and the measurement method. In Fig.
  • 1 is the eye of the patient
  • 2 is the CCD camera
  • 3 is the photomultiplier tube
  • 4 is the autocorrelator (correlator)
  • 5 is the computer (for example, FUJITSU FMV DESK POWER). )
  • 6 is a focusing lens
  • 7 is a fiber lens
  • 8 is a field stop
  • 9 is a mirror
  • 10 is a polarizer
  • 1 1 is an image stop
  • 1 2 is a shutter
  • 1 3 is interference.
  • Filters 14 a cylindrical lens (for aiming), 15 a monitor photodiode, 16 a polarizer, 17 a heat expander, 18 a fiber, and 19 a fiber
  • composition of the present invention was instilled, it was confirmed that the opacity was cured earlier than the control of the untreated example.
  • FIG. 5 shows the results of turbidity measurement by laser scattered light in a case where a traumatic cataract was produced and the composition of the present invention (Formulation Example 1) was administered for one week and a case where the composition was left as a control.
  • Fig. 5 (a) shows the autocorrelation coefficient of the instilled example
  • Fig. 5 (b) shows the autocorrelation coefficient of the untreated example.
  • the early component (A) appears strongly, the particle size of the turbidity is small, and the cataract is small.
  • the early component (A) is small, the late component (B) is strong, and the turbidity is still strong.
  • PE-200 retina potential measuring device
  • a contact lens electrode was set on the cornea of a colored rabbit as a lead electrode, a needle electrode was inserted into the ear as a ground, and a common (COMMON) (—) electrode was inserted into the forehead of the colored rabbit.
  • the ERG electroretinogram
  • the right eye served as control.
  • Fig. 6 (a) shows the results immediately before the start of corneal suction.
  • R indicates normal ERG, where R indicates right eye (no instillation), L indicates left eye (instillation), A indicates A wave, and B indicates B wave.
  • Fig. 6 (b) shows the ERG immediately after the compression is released, and
  • Fig. 6 (c) shows the ERG one week after the end of the compression.
  • composition of the present invention was instilled into the left eye for 1 week (4 times a day), and ERG was measured.
  • the right eye was left as it was without instillation, and the ERG was measured and used as a control.
  • composition of the present invention had a therapeutic effect on retinal lesions by instillation.
  • composition of the present invention has a corneal wound healing promoting effect.
  • the therapeutic composition of the present invention exerts its effects by acting on the optic nerve. As a result, it has the advantage that it can be administered directly to the eyeball with almost no side effects.
  • composition of the present invention can treat optic nerve dysfunction by a simple administration method without imposing an excessive burden on patients and doctors.
  • compositions of the present invention are also effective in treating cataracts, retinal lesions, and corneal damage.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Psychology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions thérapeutiques à usage ophtalmique ou des compositions thérapeutiques destinées au traitement des lésions cérébrales centrales. Ces compositions se caractérisent en ce qu'elles contiennent de 0 à 300 mM/l d'ions sodium, de 2,5 à 10 mM/l d'ions potassium, de 0,5 à 3 mM/l d'ions calcium, de 0,5 à 3 mM/l d'ions magnésium, de 60 à 200 mM/l d'ions chlore, de 1,5 à 6 mM/l d'ions phosphate, de 10 à 50 mM/l d'ions carbonate, de 0 à 10 mM/l de glucose et de 0,1 à 1mM/l d'oxyglutathione.
PCT/JP2000/003830 1999-06-14 2000-06-13 Compositions therapeutiques a usage ophtalmique et compositions therapeutiques destinees au traitement des lesions cerebrales centrales WO2000076454A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU51094/00A AU5109400A (en) 1999-06-14 2000-06-13 Therapeutic compositions for ophthalmic use and therapeutic compositions for brain central lesions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP11/166784 1999-06-14
JP16678499 1999-06-14

Publications (2)

Publication Number Publication Date
WO2000076454A2 true WO2000076454A2 (fr) 2000-12-21
WO2000076454A3 WO2000076454A3 (fr) 2001-06-28

Family

ID=15837622

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/003830 WO2000076454A2 (fr) 1999-06-14 2000-06-13 Compositions therapeutiques a usage ophtalmique et compositions therapeutiques destinees au traitement des lesions cerebrales centrales

Country Status (2)

Country Link
AU (1) AU5109400A (fr)
WO (1) WO2000076454A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006040839A1 (fr) * 2004-10-15 2006-04-20 Advanced Medicine Research Institute Gouttes oculaires et trousses de traitement de maladies oculaires
JP2010531810A (ja) * 2007-06-29 2010-09-30 クラレンス ピーティーワイ エルティーディー 点眼投与による神経疾患または精神神経疾患の治療または予防
US11913958B2 (en) 2017-03-30 2024-02-27 Ecs-Progastrin Sa Compositions and methods for detecting lung cancer

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4443432A (en) * 1981-10-05 1984-04-17 Alcon Laboratories, Inc. Ophthmalic irrigating solution
JPH0611704B2 (ja) * 1989-01-19 1994-02-16 参天製薬株式会社 角膜疾患治療用点眼剤
JPH0643338B2 (ja) * 1988-08-05 1994-06-08 参天製薬株式会社 抗白内障点眼剤
US5281353A (en) * 1991-04-24 1994-01-25 Allergan, Inc. Compositions and methods for disinfecting/cleaning of lenses and for destroying oxidative disinfectants
US5328701A (en) * 1992-09-10 1994-07-12 Peregrine Surgical Ltd. Tissue irrigation solution
JPH0848634A (ja) * 1994-08-05 1996-02-20 Akio Okamoto 角膜治療剤
US6261545B1 (en) * 1996-09-13 2001-07-17 Advanced Medicine Research Institute Ophthalmic compositions of neurotrophic factors, remedies for optic nerve function disorders and method for treating optic nerve function disorders
JPH10218787A (ja) * 1997-02-06 1998-08-18 Akio Okamoto 神経栄養因子による眼科用組成物

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006040839A1 (fr) * 2004-10-15 2006-04-20 Advanced Medicine Research Institute Gouttes oculaires et trousses de traitement de maladies oculaires
JP2010531810A (ja) * 2007-06-29 2010-09-30 クラレンス ピーティーワイ エルティーディー 点眼投与による神経疾患または精神神経疾患の治療または予防
US12042471B2 (en) 2007-06-29 2024-07-23 Photopharmics, Inc. Ocular treatments for neurological and neuropsychiatric disorders
US11913958B2 (en) 2017-03-30 2024-02-27 Ecs-Progastrin Sa Compositions and methods for detecting lung cancer

Also Published As

Publication number Publication date
AU5109400A (en) 2001-01-02
WO2000076454A3 (fr) 2001-06-28

Similar Documents

Publication Publication Date Title
KR100514277B1 (ko) 신경 영양 인자의 안과용 조성물, 시신경 기능 장애 치료제 및 시신경 기능 장애 치료 방법
RU2286157C2 (ru) Средства для введения в стекловидное тело для лечения или предотвращения заболеваний глаз
JPH0468288B2 (fr)
CN1382443A (zh) 钠离子通道阻断剂在制备用于局部神经麻醉或镇痛的药物中的应用
Edwards et al. Ophthalmomyiasis interna causing visual loss
JPH10218787A (ja) 神経栄養因子による眼科用組成物
RU2297813C1 (ru) Способ лечения неоваскулярной глаукомы
RU2071303C1 (ru) Способ лечения помутнений прозрачных сред глаза
RU2270025C1 (ru) Способ лечения диабетической ретинопатии
RU2575966C2 (ru) Способ лечения неоваскулярной глаукомы
WO2000076454A2 (fr) Compositions therapeutiques a usage ophtalmique et compositions therapeutiques destinees au traitement des lesions cerebrales centrales
RU2408335C1 (ru) Способ лечения возрастной макулярной дегенерации сетчатки
RU2613426C1 (ru) Интраоперационный способ профилактики послеоперационного воспаления и отека роговицы в ходе энергетической экстракции твердой катаракты (Варианты)
KR100287991B1 (ko) 안과용 아르가트로반 제제
RU2199989C1 (ru) Способ лечения заболеваний сетчатки и зрительного нерва дистрофического генеза
RU2240086C2 (ru) Способ лечения рефракторной глаукомы
RU2164117C2 (ru) Способ лечения отслойки цилиарного тела
RU2164112C1 (ru) Способ лечения постконтузионных повреждений глаза
RU2325887C2 (ru) Способ лечения неоваскулярной глаукомы
RU2219943C1 (ru) Способ лечения диабетической ретинопатии
KR20210135720A (ko) 황반변성의 완화, 억제, 치료 또는 예방용 조성물
Kavanagh et al. Detection of a congenital cystic eyeball by prenatal ultrasound in a newborn with turner’s syndrome
RU2801496C1 (ru) Способ лечения глаукомной оптической нейропатии
RU2062080C1 (ru) Способ лечения заболеваний глаза
RU2821262C1 (ru) Способ подготовки пациентов с синдромом "сухого глаза" на фоне дисфункции мейбомиевых желез к реконструктивным вмешательствам на роговице

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AU BR CA CN IL JP KR US

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AU BR CA CN IL JP KR US

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 502794

Kind code of ref document: A

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase
点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载