CN105188702A - Compositions for use in treating eye disorders using dipyridamole - Google Patents
Compositions for use in treating eye disorders using dipyridamole Download PDFInfo
- Publication number
- CN105188702A CN105188702A CN201480016302.6A CN201480016302A CN105188702A CN 105188702 A CN105188702 A CN 105188702A CN 201480016302 A CN201480016302 A CN 201480016302A CN 105188702 A CN105188702 A CN 105188702A
- Authority
- CN
- China
- Prior art keywords
- dipyridamole
- eye
- day
- disease
- compositions
- 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.)
- Granted
Links
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 229960002768 dipyridamole Drugs 0.000 title claims abstract description 60
- 239000000203 mixture Substances 0.000 title claims abstract description 37
- 208000030533 eye disease Diseases 0.000 title claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 210000001508 eye Anatomy 0.000 claims description 37
- 210000000795 conjunctiva Anatomy 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 210000002159 anterior chamber Anatomy 0.000 claims 2
- 230000003203 everyday effect Effects 0.000 description 35
- 208000005494 xerophthalmia Diseases 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 230000002596 correlated effect Effects 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 208000031973 Conjunctivitis infective Diseases 0.000 description 11
- 201000001028 acute contagious conjunctivitis Diseases 0.000 description 11
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 9
- 206010013774 Dry eye Diseases 0.000 description 9
- 208000009329 Graft vs Host Disease Diseases 0.000 description 9
- 201000002154 Pterygium Diseases 0.000 description 9
- 210000004087 cornea Anatomy 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 208000024908 graft versus host disease Diseases 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 206010002091 Anaesthesia Diseases 0.000 description 8
- 206010064996 Ulcerative keratitis Diseases 0.000 description 8
- 230000037005 anaesthesia Effects 0.000 description 8
- 201000007717 corneal ulcer Diseases 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 201000004768 pinguecula Diseases 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003889 eye drop Substances 0.000 description 6
- 230000036407 pain Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000006196 drop Substances 0.000 description 5
- 206010023332 keratitis Diseases 0.000 description 5
- 206010010741 Conjunctivitis Diseases 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 206010046851 Uveitis Diseases 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 206010069732 neurotrophic keratopathy Diseases 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 230000035807 sensation Effects 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 210000001745 uvea Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010022941 Iridocyclitis Diseases 0.000 description 3
- 201000002287 Keratoconus Diseases 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 201000004612 anterior uveitis Diseases 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 206010010984 Corneal abrasion Diseases 0.000 description 2
- 208000028006 Corneal injury Diseases 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 208000000222 Viral Eye Infections Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 206010047513 Vision blurred Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 230000037058 blood plasma level Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 210000003683 corneal stroma Anatomy 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 210000003560 epithelium corneal Anatomy 0.000 description 2
- 239000003885 eye ointment Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 206010023365 keratopathy Diseases 0.000 description 2
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical compound N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 description 2
- 210000003786 sclera Anatomy 0.000 description 2
- 239000008279 sol Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000016134 Conjunctival disease Diseases 0.000 description 1
- 208000027219 Deficiency disease Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000014260 Fungal keratitis Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 206010034944 Photokeratitis Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037508 Punctate keratitis Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 201000009310 astigmatism Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 208000024754 bloodshot eye Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000010036 cardiovascular benefit Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000004614 iritis Diseases 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 201000005111 ocular hyperemia Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
-
- 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
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses compositions for use in treating eye disorders, the compositions including an effective amount of a topically-administered dipyridamole. Preferably, the topically-administered dipyridamole is formulated as a solution. Preferably, the topically-administered dipyridamole is at least one agent selected from the group consisting of: dipyridamole, and a pharmaceutically-acceptable salt thereof. Preferably, the effective amount corresponds to a concentration of at least about 10-5 molarity. Preferably, the effective amount is based on a treatment administration of at least once every other day.
Description
Technical field
The present invention relates to the compositions being used for the treatment of disease of eye using dipyridamole.
Background technology
As known in the art, the medical condition being called as " xerophthalmia " is a kind of imbalance of tear film, and this is because tear lack or the evaporation of excessive tear, thus causes the destruction to eye surface between eyelid be associated with the symptom of eye discomfort.Current, xerophthalmia comprises two primary categories: (i) olighydria type xerophthalmia (ADDE), and (ii) vaporized strong type xerophthalmia (EDE).ADDE mainly refers to because lacrimal gland function is incomplete and can not secrete enough tear.ADDE has two main subclasses: (i) Sjorgen Cotard xerophthalmia (SSDE), and (ii) non-Sjorgen Cotard xerophthalmia (such as in graft versus host disease (GvHD) or in diabetes).EDE can be: (i) is intrinsic, owing to affecting eyelid structure or dynamic disease, or (ii) is exogenous, wherein eye surface diseases is due to some external exposures, as topical remedy's antiseptic, the wearing of contact lens, pterygium or hypovitaminosis A.
Term " corneal ulcer ", typically refers to wherein corneal epithelium, substrate or medical condition that both are dissolved because of activation and the supersecretion of colloidal sol protoenzyme and delete.Colloidal sol protoenzyme causes corneal ulcer, and bacterial collagenase and matrix metalloproteinase (MMP) are this exedens processes of known participation.
Ulcer can be promoted by the Collagen extracellular environment change caused of degrading.Such condition produces the vicious cycle of activation keratocyte and degraded corneal stroma.When antibacterial is killed by antibiotic, bacterial collagenase secretion is suppressed, and directly corneal stroma degraded is suppressed due to antibacterial.But, because most antibiotics can not suppress the activation of the keratocyte caused by the signal of organism being once sent to keratocyte from antibacterial, so observe the progress of ulcer clinically every now and then.
Cornea/conjunctival disease, the corneal epithelium deficiency disease of the etch and prolongation that comprise the repetition of cornea joins with such disease association.The repair process of cornea/conjunctival epithelium disease is related to and being lacked by the migration protective epithelium of corneal epithelial cell, follows by subsequent cell division and differentiation, causes normal cornea and conjunctival reconstruction.Corneal anesthesia becomes neurotrophic keratopathy with congenital corneal anesthesia General development.Neurotrophic keratopathy is a kind of degenerative keratopathy brought out by injury of trigeminal nerve.The innerv damage of corneal sensitivity or loss are the reasons of corneal epithelial defect, ulcer and perforation.
Pterygium is the non-cancer growth started in the limpid thin tissue (conjunctiva) of eyes.The white portion (sclera) of eyes is contained in this growth, and extends on cornea.It erects often slightly, and containing visible vessels.This problem may occur in one or two eyes.Pterygium may become inflammation and cause in calcination, stimulation or sensation eyes seemingly has exotic.If growth enough far extends to cornea, so vision may be affected.At present known except operation for pterygial radical treatment.
Pinguecula is that the scleral band of approach angle film edge on conjunctiva is yellow, slightly erects and thickens.Pinguecula usually occurs in the part between sclera and eyelid, is therefore exposed to the sun.In some cases, pinguecula becomes swelling and inflammation, i.e. a kind of patient's condition being called pinguecula inflammation.Continually, pinguecula can cause pterygial formation.The radical treatment for pinguecula except operation unknown at present.
Uveitis is the inflammation in the eyes intermediate layer being called tunica uvea (uvea) or tunica uvea (uvealtract).Tunica uvea is made up of the middle pigment blood vessel structure of eyes, and comprises iris, corpus ciliare and choroid.In western countries, anterior uveitis accounts for 50% to 90% of uveitis case, and in Asian countries, this ratio drops between 28% and 50%.Uveitis estimation is the reason of about 10 to the 20% blind case of the U.S..Pathogenic factor normally infectious (antibacterial or viral infection) or autoimmunity.Inherited genetic factors serves as the risk factor of this intractable treatment patient's condition.
In the prior art, dipyridamole { 2, two (diethanolamino)-4 of 6-, 8-bis-piperidines pyrimido [5,4-d] pyrimidine, the closely-related pyrimido-pyrimidine that is substituted and its method for making by Fischer at U.S. Patent number 3,031, teaching in 450 (hereinafter referred to as 450 of Fischer).Dipyridamole is described as a kind of nineteen sixty for early stage coronary vasodilator, and is knownly have the anticoagulant character that causes because adenosine uptake suppresses.Subsequently, in the brain medium-sized artery circulating research of a rabbit model, display dipyridamole can reduce thrombosis.These investigation cause it to use as antithrombotic agent.Dipyridamole becomes for such as prevention of stroke very soon, keeps the unobstructed of coronary bypass and valve displacement, and the therapeutic choice of the application for the treatment of for front coronary angioplasty.
In the patent publication No. EP0234854B1 (hereinafter referred to as 854 of Gilbard) of the people such as Gilbard, suggestion ring-type cAMP works as the second message,second messenger of exocytosis in lachrymal gland, and action is to increase lacrimal secretion.CAMP is by di-phosphate ester enzymatic degradation.Therefore can think, cAMP level in the born of the same parents suppressing phosphodiesterase can cause increasing, and then promote lacrimal secretion.Dipyridamole is considered to serve as phosphodiesterase inhibitor, and is considered to by its some cardiovascular benefits of this mechanisms play.
But, at the 19th page of the patent publication No. WO2007/140181 (hereinafter referred to as 181 of Leung) of Leung, it discloses compared to contrast, can ignore the impact of cAMP after adding dipyridamole.Only the combination of caffeine and dipyridamole produces the desired effects of external reduction cAMP, and this is assumed to be the cellular level that instruction increases cAMP.
By expecting, there is the compositions being used for the treatment of disease of eye using dipyridamole.This compositions and treatment indication will especially overcome the problem of above-mentioned with such disease association connection.
Summary of the invention
The object of the present invention is to provide the compositions being used for the treatment of disease of eye and treatment indication that use dipyridamole.
Detailed description of the invention
For the sake of clarity, term " disease of eye " is special in use definition herein, include, but is not limited to scleritis, graft versus host disease (GvHD), keratitis, corneal ulcer, corneal abrasion, snow blindness, ThygesonShi superficial punctate keratopathy, cornea neovascularization, FuchShi malnutrition, keratoconus, keratoconjunctivitis (xerophthalmia), iritis, corneal anesthesia, neurotrophic keratopathy, blood-shot eye illness, pink eye disease, fungal keratitis, xerophthalmia (xerophthalmia), retinoblastoma, uveitis, pterygium, any disease of keratopathy and pinguecula.
In addition, it should be noted that term " exemplary " is used to refer to the example of embodiment and/or enforcement in this article, and and do not mean that and must pass on a more preferably use-case.Similarly, term " preferably " is used to refer to an expection embodiment and/or the example that sub-elects of enforcement in this article, and and do not mean that and must pass on a more preferably use-case.Therefore, from should be understood that " exemplary " and " preferably " may be used on multiple embodiment and/or enforcement in this article above.
Dipyridamole, easily from gastrointestinal absorption, reaches human plasma peak level at oral administration after 1 to 3 hours.Peak serum level is dose dependent, and scope is from the 1.6g/mL after about 0.5g/mL to the 75mg dosage after 25mg dosage.Blood level alters a great deal, and may depend on food intake and gastrointestinal peristalsis.Eat on an empty stomach and may cause higher blood level.After intravenous (IV) administration, distribution half-life is about 25 minutes in the mankind, and after oral administration, is about 3 hours.When reaching 60 hours after the blood plasma level IV following medicine or oral administration 20-50mg, blood plasma level is three index decreased, its half-life be 5 minutes (only IV), 53 minutes and about 10 to 12 hours.The volume of distribution is about 140L, and wherein about 92 to 99% in conjunction with plasma protein, mainly α 1 acidoglycoprotein.Dipyridamole typical every day oral dosage ranges from 100 to 400mg.
Dipyridamole is hardly water-soluble (water solubility is 8.17mg/L (people (1996) such as Meylan, WM)), but is fairly dissolved in methanol.This is find a kind of appropriate method for ophthalmic applications to create challenge, the aqueous solution preferably sent via single in ophthalmic applications.Embodiment of the present invention provide the compositions and the treatment indication that use dipyridamole to be used for the treatment of disease of eye.After measured, by regulating the pH of aqueous solution to about 6.6 (6.5 to 6.7), dipyridamole fully dissolves in aqueous.The native pH of tear is 7.4; But, as long as the pH value of drug administration remains in the scope of 6.6 to 7.8, user can not the not feel well (people such as SampathKumar, " the up-to-date challenge of ocular drug delivery system and progress (RecentChallengesandAdvancesinOphthalmicDrugDeliverySyste m) ", at ThePharmaInnovation, 1st volume, in No. 4 (2012)).
Other method can be used to realize water solublity, and as ultrasonic mixing, or dipyridamole to be dissolved in wherein dipyridamole be solvable methanol, chloroform, acetic acid, DMSO or other supporting agent, then adds water or saline, then removes all or part supporting agent.Another kind method can to relate in water/saline mixing before polishing compounds to nanoparticle size.It should be noted that when preparing rarer exemplary formulation C and D described below, few acidify is necessary.Although often preferred aqueous solutions is used for eyes instillation, the dipyridamole be prepared in oil or emulsifiable paste matrix is the another kind of method overcoming water solublity challenge.
According to aspects of the present invention, find that dipyridamole can effectively treat eye medical condition when in normal saline preparation during local application.The local application of dipyridamole can be used for treating the xerophthalmia caused by the relevant xerophthalmia of such as graft versus host disease (GvHD), diabetes, anaphylaxis conjunctivitis, contact lens and Sjorgen Cotard.
In an exemplary embodiment of the present invention, local dipyridamole also may be used for treating by such as: viral infection, bacteriological infection, fungal infection, wear the corneal ulcer that damage that contact lens causes, traumatic injury and parasitic infection causes.In addition, local dipyridamole also can be used for treatment pterygium, corneal anesthesia and cornea neovascularization.
Therefore, according to the present invention, provide a kind of compositions for being used for the treatment of disease of eye in the very first time, described compositions comprises: the dipyridamole of the local application of (a) effective dose.Preferably, the dipyridamole of described local application is deployed into solution.Preferably, the dipyridamole of described local application is that at least one is selected from by the medicament of the following group formed: dipyridamole and its medicinal acceptable salt.Preferably, described effective dose corresponds at least about 10
-5the concentration of molar concentration.Preferably, described effective dose uses based at least every other day treatment once.These and other embodiment will from following detailed description and example apparent.
preferred embodiment explanation
The present invention relates to the compositions being used for the treatment of disease of eye using dipyridamole.According to the present invention, in these compositionss, purposes and advantage can illustrate with reference to enclosing and understand better.This explanation should not be considered to have limited significance, but just to the object of General Principle of the present invention is described, because scope of the present invention is preferably defined by the appended claims.Exemplary of the present invention is described in detail in following exemplary formulation.
Exemplary formulation A:
Prepare dipyridamole eye drop as follows.1g citric acid is blended in 100mL saline (aseptic aqueous solution of 0.9%w/v sodium chloride), obtaining pH is 6.7.Weigh 8.5mg dipyridamole, the aseptic of carrying out 30 minutes irradiates UVB, and is diluted in 100mL saline.Then this solution is carried out sterilizing by 0.22 zut filter, produce every milliliter of solution containing 85mcg dipyridamole.With dropper, one (being equivalent to about 0.05mL) is administered to eyes.
Exemplary formulation B:
Prepare dipyridamole eye drop as follows.1g citric acid is blended in 100mL saline (aseptic aqueous solution of 0.9%w/v sodium chloride), obtaining pH is 6.7.Weigh 4.25mg dipyridamole, the aseptic of carrying out 30 minutes irradiates UVB, and is diluted in 100mL saline.Then this solution is carried out sterilizing by 0.22 zut filter, produce every milliliter of solution containing 42.5mcg dipyridamole.With dropper, one (being equivalent to about 0.05mL) is administered to eyes.
Exemplary formulation C:
Prepare dipyridamole eye drop as follows.1g citric acid is blended in 100mL saline (aseptic aqueous solution of 0.9%w/v sodium chloride), obtaining pH is 6.7.Weigh 2.125mg dipyridamole, the aseptic of carrying out 30 minutes irradiates UVB, and is diluted in 100mL saline.Then this solution is carried out sterilizing by 0.22 zut filter, produce every milliliter of solution containing 21.25mcg dipyridamole.With dropper, one (being equivalent to about 0.05mL) is administered to eyes.
Exemplary formulation D:
Prepare dipyridamole eye drop as follows.1g citric acid is blended in 100mL saline (aseptic aqueous solution of 0.9%w/v sodium chloride), obtaining pH is 6.7.Weigh 1.0625mg dipyridamole, the aseptic of carrying out 30 minutes irradiates UVB, and is diluted in 100mL saline.Then this solution is carried out sterilizing by 0.22 zut filter, produce every milliliter of solution containing 10.625mcg dipyridamole.With dropper, one (being equivalent to about 0.05mL) is administered to eyes.
Result:
Suffer from the be correlated with human male of xerophthalmia of GvHD for five to treat for twice every day on both sides with a dripping agent A.The subjectivity realizing dry eye condition in half an hour is alleviated.Described needs of patients subsequent applications, every day twice.Use after 3 days, eyes rubescent (or pink eye disease) disappears.
The be correlated with female human of xerophthalmia treats for twice on both sides by a formulation C every day for two having diabetes.The alleviation of dry eye condition is realized in one hour.Described needs of patients subsequent applications, every day twice.Use after 5 days, eyes rubescent (or pink eye disease) disappears.
The be correlated with female human of xerophthalmia once treats the both sides next day with a dripping agent B for having diabetes.The alleviation of dry eye condition is realized in 20 minutes.Described needs of patients subsequent applications, the next day once.Use after 10 days, eyes rubescent (or pink eye disease) disappears.Maintain with the next day use and once continue.
Suffer from the human male that viral eye infection has a corneal ulcer for one to treat for twice every day on both sides with a dripping agent B.Stopping is oozed out in 8 hours.Described needs of patients subsequent applications, every day twice.Use after 4 days, eyes rubescent (or pink eye disease) disappears, and eyes were completely recovered in 5 days.
Eye are suffered from the human male that pterygium has relevant xerophthalmia and pink eye disease and are treated for twice every day with a dripping agent B.The alleviation of dry eye condition is realized in one day.Described needs of patients subsequent applications, every day twice.Use after 10 days, eyes rubescent (or pink eye disease) disappears.After using 6 weeks, pterygium has shunk the about size of half, and continues to reduce size under uninterrupted use.
Eye are suffered from the female human that pterygium has relevant xerophthalmia and an inflammation and are treated for twice every day by a formulation C.The alleviation of dry eye condition is realized in two days.Described needs of patients subsequent applications, every day twice.After using 8 weeks, pterygium has shunk the about size of half, and continues to reduce size under uninterrupted use.
Eyes are suffered from population of deeper corneal ulcer and are accompanied the human male of interstitial intervention to treat for three times every day with a dripping agent A.In 24 hour, realize pain and stimulate alleviating.Described needs of patients subsequent applications, every day twice.Use after 7 days, cornea re-epithelilization completely.
The be correlated with women of corneal anesthesia (neurotrophic keratopathy) treats once a day by a formulation C for three having diabetes.The symptom of corneal anesthesia starts to improve in 2-3 days.Described needs of patients subsequent applications, every day twice.Use after about 3 weeks, described patient's report symptom complete incidence graph.
The be correlated with male of neovascularization treats for twice with a dripping agent A every day for having diabetes.When use checked after 4 weeks, no longer visible with slit lamp examination abnormal vascular.
Suffer from the human male that viral eye infection has a corneal abrasion (namely corneal ulcer occurring) for two to treat for twice every day on both sides with a dripping agent A.Stopping is oozed out in 5 hours.Described needs of patients subsequent applications, every day twice.Use after 2-3 days, eyes rubescent (or pink eye disease) disappears, and eyes were completely recovered in 5-6 days.
The female human that eye suffer from corneal ulcer treats for twice with a dripping agent A every day.In one day, realize pain and stimulate alleviating.Described needs of patients subsequent applications, every day twice.Use after 7 days, ulcer is completely recovered.
The be correlated with human male of xerophthalmia treats for twice on both sides with a dripping agent A every day for four having diabetes.The average alleviation realizing dry eye condition within half an hour.Described needs of patients subsequent applications, every day twice.Average use is after one week, and eyes rubescent (or pink eye disease) disappears completely.
The be correlated with women of corneal anesthesia treats once a day with a dripping agent A for two having diabetes.The symptom of corneal anesthesia starts to improve in 2 days.Use after about one week, described patient's report symptom complete incidence graph.
The be correlated with human male of neovascularization treats for twice by a formulation C every day for having diabetes.Described needs of patients subsequent applications, every day twice.When use checked after 16 days, check that abnormal vascular is no longer visible with slit lamp photography.
Suffer from the be correlated with human patients of xerophthalmia of GvHD for six to treat for twice every day on both sides by a formulation C.The alleviation of dry eye condition is realized in one hour.Described needs of patients subsequent applications, every day twice.Average use is after one week, and eyes rubescent (or pink eye disease) disappears.
The human male that eyes suffer from anterior uveitis treats for three times by a formulation C every day.The alleviation of pain is realized in three days.Blurred vision is solved in 7 days.Seemed to solve inflammation completely in 14 days.Described patient continues subsequent applications, every day twice, to keep alleviating.
The human male that eyes suffer from anterior uveitis treats for three times with a dripping agent B every day.The alleviation of pain is realized in two days.Blurred vision is solved in 14 days.Seemed to solve inflammation completely in 18 days.Described patient continues subsequent applications, every day twice, to keep alleviating.
Suffer from the be correlated with human patients of xerophthalmia of GvHD for three to treat for twice every day on both sides with a dripping agent D.The alleviation of dry eye condition is realized in one hour.Described needs of patients subsequent applications, every day twice.Average use is after one week, and eyes rubescent (or pink eye disease) disappears.
Additional preferred embodiment and experiment
Dipyridamole eye drop prepares by dissolving dipyridamole in sterilized water.Adjust pH as required to realize solubility.Prepare some concentration, scope is from 5mcg/ml to 200mcg/ml.Follow sterile procedure.
Dipyridamole eye ointment is by mixing dipyridamole in the substrate of the yellow soft paraffin of (8:1:1) ratio, liquid paraffin and lanoline and preparing.Prepare some concentration, scope is from 5mcg/ml to 200mcg/ml.Follow sterile procedure.
Dipyridamole eye drop (one [about 0.05mL], every day one to three times) or dipyridamole eye ointment (about 0.1 to 0.3mL [every day one to twice]) are administered to and suffer from SjorgenShi and be correlated with in the subject eye of xerophthalmia, nonspecific keratitis, keratoconus or anaphylaxis conjunctivitis.The concentration used increases gradually under allowing.
Result
SjorgenShi is correlated with xerophthalmia: through going through slightly of short duration sensation of pricking after using drop/ointment.Using alleviating dry eye symptom in beginning in hour.Continuous use, after about 7 days, becomes complete incidence graph, and some patients continues administration once a day and time limit (every 3-4 days) administration in other patient.
Nonspecific keratitis: through going through slightly of short duration sensation of pricking after using drop/ointment.Using in 1 to 2 hours the attenuating intensity experiencing pain.After regularly using (spaced apart several hours) drop/ointment for 3 to 4 times, total pain relief.Uninterruptedly use in 2 to 7 days and realize solving keratitis completely.
Keratoconus: daily (every day one to twice) continue within 3 months, cause astigmatism to be improved, make two experimenters cylinder reduce by 1/4th arrive half.
Conjunctivitis (non-specific): through going through slightly of short duration sensation of pricking after using drop/ointment.Start conjunctivitis symptoms (itch, burn feeling or delacrimation) partial rcsponse using in one hour.Use lasting every day one to twice.Use after two to four days, all symptoms comprise oozing out to be alleviated.
Although the present invention is described relative to the embodiment of limited quantity, it should be understood that, many changes of the present invention, amendment and other application can be carried out.
In this manual, as paragraph [0002], [0003], [0004], [0005], [0006], [0007], [0008], [0014], [0019], [0020], [0027], [0028], [0029], [0030], [0031], [0032], [0033], [0034], [0035], [0036], [0038], [0039], [0040], [0041], [0042], [0043], [0044], [0047], [0048], [0049], [0050] and [0051] known leading portion (comprising conjunctiva) and/or lacrimal system that can affect eyes of all disease of eye of listing.
Industrial usability
By using the compositions of dipyridamole to be applied in treatment disease of eye, it is a kind of innovation overcoming the problem joined with such disease association.
Claims (10)
1. be used for the treatment of a compositions for disease of eye, described compositions comprises:
The dipyridamole of the local application of effective dose.
2. compositions according to claim 1, the dipyridamole of wherein said local application is deployed into solution.
3. compositions according to claim 1, the dipyridamole of wherein said local application is that at least one is selected from by the medicament of the following group formed: dipyridamole and its medicinal acceptable salt.
4. compositions according to claim 1, wherein said effective dose corresponds at least about 10
-5the concentration of molar concentration.
5. compositions according to claim 1, wherein said effective dose is based at least every other day therapeutic administratp once.
6. be used for the treatment of a compositions for lacrimal system and anterior chamber of eye disease of eye, described compositions comprises:
The dipyridamole of the local application of effective dose can affect the lacrimal system of eyes with treatment and comprise the disease of eye of anterior chamber of eye of conjunctiva.
7. compositions according to claim 6, the dipyridamole of wherein said local application is deployed into solution.
8. compositions according to claim 6, the dipyridamole of wherein said local application is that at least one is selected from by the medicament of the following group formed: dipyridamole and its medicinal acceptable salt.
9. compositions according to claim 6, wherein said effective dose corresponds at least about 10
-5the concentration of molar concentration.
10. compositions according to claim 6, wherein said effective dose is based at least every other day therapeutic administratp once.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL225179 | 2013-03-12 | ||
| IL225179A IL225179A (en) | 2013-03-12 | 2013-03-12 | Compositions for use in treating eye disorders using dipyridamole |
| PCT/IB2014/059645 WO2014141079A1 (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105188702A true CN105188702A (en) | 2015-12-23 |
| CN105188702B CN105188702B (en) | 2019-03-26 |
Family
ID=48916407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480016302.6A Expired - Fee Related CN105188702B (en) | 2013-03-12 | 2014-03-11 | Compositions for treating ocular diseases using dipyridamole |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP2968328A4 (en) |
| JP (1) | JP6820658B2 (en) |
| KR (2) | KR20150126021A (en) |
| CN (1) | CN105188702B (en) |
| AU (1) | AU2014229371B2 (en) |
| BR (1) | BR112015022084A2 (en) |
| CA (1) | CA2905594A1 (en) |
| CL (1) | CL2015002627A1 (en) |
| EA (1) | EA035966B1 (en) |
| IL (1) | IL225179A (en) |
| MX (1) | MX2015012716A (en) |
| MY (1) | MY182591A (en) |
| SG (2) | SG11201507092QA (en) |
| WO (1) | WO2014141079A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024125322A1 (en) * | 2022-12-16 | 2024-06-20 | 智泽童康(广州)生物科技有限公司 | Dipyridamole for preventing and treating allergic and/or inflammatory diseases and preparation thereof |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016119701A1 (en) | 2015-01-28 | 2016-08-04 | Realinn Life Science Limited | COMPOUNDS FOR ENHANCING PPARγ EXPRESSION AND NUCLEAR TRANSLOCATION AND THERAPEUTIC USE THEREOF |
| US20180092776A1 (en) | 2016-09-30 | 2018-04-05 | Sara Heikali | Method and device for treating and managing diseased ocular tissue |
| WO2021001805A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations and their methods of preparation |
| WO2021001806A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations with reduced impurities |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0672417A1 (en) * | 1994-03-17 | 1995-09-20 | Rohto Pharmaceutical Co., Ltd. | Reduction of elevated intraocular pressure |
| US5780450A (en) * | 1995-11-21 | 1998-07-14 | Alcon Laboratories, Inc. | Use of adenosine uptake inhibitors for treating retinal or optic nerve head damage |
| CN101355876A (en) * | 2005-11-09 | 2009-01-28 | 康宾纳特克斯公司 | Methods, compositions, and kits for the treatment of medical conditions |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060104968A1 (en) * | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| WO2010056710A1 (en) * | 2008-11-11 | 2010-05-20 | Biovista, Inc. | Compositions and methods for treating eye diseases |
| EP2363126A1 (en) * | 2010-03-04 | 2011-09-07 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Composition comprising as active ingredient L-carnitine in combination with hydroxykynurenine-O-beta-DL-glucoside, for the prevention and/or treatment of pathologies of the eye due to ultraviolet radiation |
-
2013
- 2013-03-12 IL IL225179A patent/IL225179A/en active IP Right Grant
-
2014
- 2014-03-11 EP EP14764673.1A patent/EP2968328A4/en not_active Withdrawn
- 2014-03-11 KR KR1020157027571A patent/KR20150126021A/en not_active IP Right Cessation
- 2014-03-11 KR KR1020217001495A patent/KR20210010638A/en not_active Application Discontinuation
- 2014-03-11 BR BR112015022084A patent/BR112015022084A2/en active Search and Examination
- 2014-03-11 WO PCT/IB2014/059645 patent/WO2014141079A1/en active Application Filing
- 2014-03-11 SG SG11201507092QA patent/SG11201507092QA/en unknown
- 2014-03-11 CA CA2905594A patent/CA2905594A1/en not_active Abandoned
- 2014-03-11 SG SG10201706937UA patent/SG10201706937UA/en unknown
- 2014-03-11 EA EA201591653A patent/EA035966B1/en unknown
- 2014-03-11 MY MYPI2015002196A patent/MY182591A/en unknown
- 2014-03-11 CN CN201480016302.6A patent/CN105188702B/en not_active Expired - Fee Related
- 2014-03-11 JP JP2015562486A patent/JP6820658B2/en not_active Expired - Fee Related
- 2014-03-11 AU AU2014229371A patent/AU2014229371B2/en not_active Ceased
- 2014-03-11 MX MX2015012716A patent/MX2015012716A/en unknown
-
2015
- 2015-09-11 CL CL2015002627A patent/CL2015002627A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0672417A1 (en) * | 1994-03-17 | 1995-09-20 | Rohto Pharmaceutical Co., Ltd. | Reduction of elevated intraocular pressure |
| US5780450A (en) * | 1995-11-21 | 1998-07-14 | Alcon Laboratories, Inc. | Use of adenosine uptake inhibitors for treating retinal or optic nerve head damage |
| CN101355876A (en) * | 2005-11-09 | 2009-01-28 | 康宾纳特克斯公司 | Methods, compositions, and kits for the treatment of medical conditions |
Non-Patent Citations (1)
| Title |
|---|
| 王立强等: "潘生丁滴眼液的制备及临床应用", 《中国医院药学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024125322A1 (en) * | 2022-12-16 | 2024-06-20 | 智泽童康(广州)生物科技有限公司 | Dipyridamole for preventing and treating allergic and/or inflammatory diseases and preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014141079A1 (en) | 2014-09-18 |
| EP2968328A1 (en) | 2016-01-20 |
| SG10201706937UA (en) | 2017-09-28 |
| SG11201507092QA (en) | 2015-10-29 |
| IL225179A (en) | 2017-01-31 |
| EA035966B1 (en) | 2020-09-07 |
| KR20150126021A (en) | 2015-11-10 |
| KR20210010638A (en) | 2021-01-27 |
| BR112015022084A2 (en) | 2017-07-18 |
| AU2014229371A1 (en) | 2015-10-29 |
| CN105188702B (en) | 2019-03-26 |
| AU2014229371B2 (en) | 2018-05-10 |
| CL2015002627A1 (en) | 2016-03-11 |
| IL225179A0 (en) | 2013-06-27 |
| MY182591A (en) | 2021-01-26 |
| JP6820658B2 (en) | 2021-01-27 |
| MX2015012716A (en) | 2016-07-06 |
| EA201591653A1 (en) | 2017-05-31 |
| JP2016514123A (en) | 2016-05-19 |
| EP2968328A4 (en) | 2016-11-23 |
| CA2905594A1 (en) | 2014-09-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5583310B2 (en) | Ophthalmic formulation for prevention and treatment of ocular symptoms | |
| EP1904108B1 (en) | Ophthalmological formulation comprising methylsulfonylmethane and ciprofloxacin | |
| US6540990B2 (en) | Physiological method of improving vision | |
| CN105188702A (en) | Compositions for use in treating eye disorders using dipyridamole | |
| US10973758B2 (en) | Methods of eye treatment using therapeutic compositions containing dipyridamole | |
| US9254289B2 (en) | Methods for treating eye disorders using dipyridamole | |
| RU2485939C1 (en) | Disulfiram and taurine-containing ophthalmological medication in form of eye drops | |
| US6605640B2 (en) | Method of treating certain eye diseases | |
| KR20230007963A (en) | Pharmaceutical composition for preventing or treating ocular disease comprising enavogliflozin | |
| EP4364722A1 (en) | Pharmaceutical composition for preventing or treating diabetic eye disease comprising sglt-2 inhibitor | |
| CN1459291A (en) | Eyedrops containing low molecular weight heparin, and its prepn. method | |
| AU2021451276A1 (en) | Pharmaceutical use of cord blood immunosuppressive cell | |
| Apel | A child with itchy eyes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170904 Address after: Rehovot Applicant after: O. D. Okaradis Caffrey Co. Address before: New jersey, USA Applicant before: Raymond Leaf |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190326 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |