IL225179A - Compositions for use in treating eye disorders using dipyridamole - Google Patents
Compositions for use in treating eye disorders using dipyridamoleInfo
- Publication number
- IL225179A IL225179A IL225179A IL22517913A IL225179A IL 225179 A IL225179 A IL 225179A IL 225179 A IL225179 A IL 225179A IL 22517913 A IL22517913 A IL 22517913A IL 225179 A IL225179 A IL 225179A
- Authority
- IL
- Israel
- Prior art keywords
- eye
- dipyridamole
- comeal
- twice daily
- drop
- Prior art date
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
- A61K31/33—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)
Description
APPLICATION FOR PATENT Title: COMPOSITIONS FOR USE IN TREATING EYE DISORDERS USING DIPYRIDAMOLE FIELD AND BACKGROUND OF THE INVENTION The present invention relates to compositions for use in treating eye disorders using dipyridamole.
As known in the art, the medical condition referred to as “dry eye” is a disorder of the tear film due to tear deficiency or excessive tear evaporation which causes damage to the interpalpebral ocular surface associated with symptoms of ocular discomfort. Currently, dry eye includes two major classes: (i) aqueous tear-deficient dry eye (ADDE), and (ii) evaporative dry eye (EDE). ADDE refers mainly to a failure of sufficient tear secretion due to lacrimal dysfunction. ADDE has two major subclasses, Sjogren’s Syndrome dry eye (SSDE) and non-SS dry eye (such as in Graft-versus-Host Disease (GvHD) or in diabetes mellitus). EDE may be: (i) intrinsic, due to diseases affecting lid structures or dynamics, or (ii) extrinsic, in which ocular surface disease occurs due to some extrinsic exposure, such as topical drug preservatives, contact lens wear, pterygium, or vitamin A deficiency.
The term “comeal ulcer” usually refers to the medical condition in which the comeal epithelium, stroma, or both are lysed and deleted by the activation and hypersecretion of collagenolytic enzyme. The collagenolytic enzyme causing comeal ulcer, bacterial collagenase, and matrix metalloproteases (MMPs) are known to be involved in the ulcerative process.
The changes in the extracellular environment caused by the degradation of stromal collagen promote ulcers. Such conditions produce a vicious circle of activation of comeal stromal cells and degradation of comeal stroma.
When the bacteria are killed by antibiotics, secretion of bacterial collagenase is suppressed, and direct comeal stroma degradation due to the bacteria is suppressed. However, since most antibiotics cannot suppress activation of comeal stromal cell caused by the biological signals once transmitted from bacteria to comeal stromal cells, progression of ulcer is clinically observed from time to time.
The comeal/conjunctival diseases, including a repeated erosion of the cornea and a prolonged comeal epithelial deficiency, are associated with such disorders. The repairing process of the comeal/conjunctival epithelial disorders involves the coverage of the epithelial deficiency by the migration of comeal epithelial cells, followed by a subsequent cell division and differentiation, resulting in reconstitution of normal cornea and conjunctiva.
Comeal anesthesia and congenital comeal anesthesia usually develop into neurotrophic keratopathy. Neurotrophic keratopathy is a degenerative comeal disease induced by an impairment of the trigeminal nerve. Impairment or loss of comeal sensory innervation is responsible for comeal epithelial defects, ulcers, and perforations.
A pterygium is a non-cancerous growth that starts in the clear, thin tissue (conjunctiva) of the eye. This growth covers the white part of the eye (sclera), and extends onto the cornea. It is often slightly raised, and contains visible blood vessels. The problem may occur in one or both eyes. Pterygium may become inflamed and cause burning, irritation, or a feeling like there’s something foreign in the eye. Vision may be affected if the grows extends far enough onto the cornea. There is at present no known curative treatment for pterygium other than surgery.
A pinguecula is a yellowish, slightly-raised thickening of the conjunctiva on the sclera, close to the edge of the cornea. Pingueculae typically occur on the part of the sclera that is between the eyelids, and therefore is exposed to the sun. In some cases, pingueculae become swollen and inflamed, a condition called pingueculitis. Frequently, pingueculae can lead to the formation of pterygia. There is at present no known curative treatment for pinguecula other than surgery.
Uveitis is inflammation of the middle layer of the eye, called the uvea or uveal tract. The uvea consists of the middle, pigmented, vascular structures of the eye, and includes the iris, ciliary body, and choroid. In western countries, anterior uveitis accounts for between 50% and 90% of uveitis cases, while in Asian countries the proportion drops to be between 28% and 50%.
Uveitis is estimated to be responsible for approximately 10-20% of the cases of blindness in the United States. The cause is generally infectious (bacterial or viral infection) or autoimmune. Genetic factors act as a predisposing factor for this difficult-to-treat condition.
In the prior art, dipyridamole {2,6-bis(diethanolamino)-4,8-dipiperidino-pyrimido[5,4-d]pyrimidine}, closely related substituted pyrimido-pyrimidines, and their preparation are taught by Fischer in US Patent No. 3,031,450 (hereinafter referred to as Fischer ’450). Dipyridamole was introduced as a coronary vasodilator in the early 1960s, and is well known to have platelet aggregation inhibitor properties due to the inhibition of adenosine uptake. Subsequently, dipyridamole was shown to reduce thrombus formation in a study of arterial circulation of the brain in a rabbit model. These investigations led to its use as an anti-thrombotic agent. Dipyridamole soon became the therapy of choice for such applications as stroke prevention, maintaining the patency of coronary bypass and valve-replacement, as well as for treatment prior to coronary angioplasty.
In Patent Publication No. EP 0234854 B1 by Gilbard et al. (hereinafter referred to as Gilbard ’854), it is suggested that cyclic cAMP functions as a second messenger for exocytosis in the lacriminal gland, and acts to increase tear secretion. cAMP is degraded by phosphodiesterases. It is therefore thought that suppressing phosphodiesterases can result in increased intracellular cAMP levels, and thus enhance tear secretion. Dipyridamole is believed to act as a phosphodiesterase inhibitor, and is thought to exert some of its cardiovascular benefits via this mechanism. However, on page 19 of Patent Publication No. WO 2007/140181 by Leung (hereinafter referred to as Leung ’181), it is disclosed that there was a negligible effect on cAMP after the addition of dipyridamole in comparison to a control. Only a combination of caffeine and dipyridamole yielded the desired effect of decreasing cAMP in-vitro, which is assumed to indicate increased cellular levels of cAMP.
W02010056710 describes compositions and methods and uses for treating a patient with one or more inflammatory eye disorders and/or degenerative eye diseases.
US 5438060 describes a method of reducing elevated intraocular pressure which comprises administering drops containing dipyridamole to patients suffering from abnormally elevated intraocular pressure. A pharmaceutical formulation containing dipyridamole as an essential component is also described.
It would be desirable to have compositions for use in treating eye disorders using dipyridamole. Such compositions and treatment indications would, inter alia, overcome the problems mentioned above associated with such ailments.
SUMMARY OF THE INVENTION It is the purpose of the present invention to provide compositions and treatment indications for use in treating eye disorders using dipyridamole.
In the interest of clarity, the term “eye disorder” is specifically defined for use herein to include, but not be limited to, any ailment of Scleritis, Graft-versus-Host Disease (GvHD), keratitis, comeal ulcer, comeal abrasion, snow blindness, Thygeson’s superficial punctuate keratopathy, comeal neovascularization, Fuch’s dystrophy, keratoconus, keratoconjunctivitis sicca (dry eye), iritis, comeal anesthesia, neurotrophic keratopathy, red eye, pink eye, keratomycosis, xeropthalmia, retinoblastoma, uveitis, pterygium, keratopathy, and pingueculae.
Furthermore, it is noted that the term “exemplary” is used herein to refer to examples of embodiments and/or implementations, and is not meant to necessarily convey a more-desirable use-case. Similarly, the term “preferred” is used herein to refer to an example out of an assortment of contemplated embodiments and/or implementations, and is not meant to necessarily convey a more-desirable use-case. Therefore, it is understood from the above that “exemplary” and “preferred” may be applied herein to multiple embodiments and/or implementations.
Dipyridamole is readily absorbed from the gastrointestinal tract, reaching peak plasma levels in humans 1-3 hours following oral administration. Peak plasma levels are dose dependent and range from about 0.5pg/mL after a 25mg dose to 1.6pg/mL after a 75mg dose. Blood levels are quite variable, possibly depending on food intake and gastrointestinal peristalsis. Ingestion on an empty stomach may result in higher blood levels. Following intravenous (IV) administration, the distribution half-life in humans is about 25 minutes, and after oral administration, is about 3 hours. When plasma levels of drug are followed for up to 60 hours after IV or oral administration of 20-5 Omg, plasma levels decline tri-exponentially with half-lives of 5 minutes (IV only), 53 minutes, and about 10-12 hours. The volume of distribution is about 140L with about 92 to 99% binding to plasma proteins, primarily alphal-acid glycoprotein. Typical daily oral doses of dipyridamole range from 100-400mg.
Dipyridamole is practically insoluble in water (water solubility is 8.17mg/L (Meylan, WM ET AL. (1996))), and very soluble in methanol. This creates a challenge for finding a suitable method for ocular application in which an aqueous solution delivered via single drops is preferred.
Embodiments of the present invention provide compositions and treatment indications for use in treating eye disorders using dipyridamole. It was determined that by adjusting the pH of the aqueous solution to ~6.6 (6.5-6.7), dipyridamole fully dissolves in the aqueous solution. The natural pH of tear fluid is 7.4; however, discomfort for the user will not be felt as long as the pH of the administered medication stays in the range of 6.6-7.8 (Sampath Kumar et al, “Recent Challenges and Advances in Ophthalmic Drug Delivery System,” in The Pharma Innovation, Vol. 1, No. 4 (2012)).
Other methods may be used to achieve water solubility such as ultrasonic mixing, or dissolving dipyridamole in methanol, chloroform, acetic acid, DMSO, or other carriers in which the dipyridamole is soluble, followed by adding water or saline, and then removing all or part of the carrier. Another method may involve grinding the compound to a nano-particle size prior to mixing in water/saline. It should be noted that when preparing the more dilute Exemplary Formulations C & D described below, less acidification was required. While aqueous solutions tend to be preferred for ocular instillation, preparing the dipyridamole in an oil or cream base is another method to overcome the aqueous solubility challenge.
In accordance with aspects of the present invention, dipyridamole was found to be effective in treating ocular medical conditions when applied topically in physiological saline formulations. Topical application of dipyridamole may serve to treat dry eye caused by, for example, Graft-versus-Host Disease (GvHD), diabetes, allergic conjunctivitis, contact lens-related dry eye, and Sjorgen’s syndrome.
In an exemplary embodiment of the present invention, topical dipyridamole may also be used to treat comeal ulcers resulting from, for example: viral infection, bacterial infection, fungal infection, injury resulting from wearing contact lenses, traumatic injury, and parasite infection. Moreover, topical dipyridamole may also be used for the treatment of pterygium, comeal anesthesia, and comeal neovascularization.
Therefore, according to the present invention, there is provided for the first time a composition for use in treating eye disorders, the composition including: (a) 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 105 molarity.
Preferably, the effective amount is based on a treatment administration of at least once every other day.
These and further embodiments will be apparent from the detailed description and examples that follow.
DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention relates to compositions for use in treating eye disorders using dipyridamole. The aspects, uses, and advantages for such compositions, according to the present invention, may be better understood with reference to the accompanying description.
The description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the present invention is best defined by the appended claims. Exemplary embodiments of the present invention are detailed below in the following exemplary formulations.
EXEMPLARY FORMULATON A: Dipyridamole eye drops were prepared as follows lg of citric acid was mixed in lOOmL saline (0.9% w/v sodium chloride in sterile water) to obtain a pH of 7.7. 8.5mg of dipyridamole was weighed, irradiated by UVB for 30 minutes for sterility, and diluted in the lOOmL saline. This solution was then filtered through a 0.22 micron filter for sterilization, resulting in a solution containing 85mcg of dipyridamole per mL. Using a dropper, one drop (equivalent to approximately 0.05mL) was applied to the eye.
EXEMPLARY FORMULATON B: Dipyridamole eye drops were prepared as follows lg of citric acid was mixed in lOOmL saline (0.9% w/v sodium chloride in sterile water) to obtain a pH of 7.7. 4.25mg of dipyridamole was weighed, irradiated by UVB for 30 minutes for sterility, and diluted in the lOOmL saline. This solution was then filtered through a 0.22 micron filter for sterilization, resulting in a solution containing 42.5mcg of dipyridamole per mL. Using a dropper, one drop (equivalent to approximately 0.05mL) was applied to the eye.
EXEMPLARY FORMULATON C: Dipyridamole eye drops were prepared as follows lg of citric acid was mixed in lOOmL saline (0.9% w/v sodium chloride in sterile water) to obtain a pH of 7.7. 2.125mg of dipyridamole was weighed, irradiated by UVB for 30 minutes for sterility, and diluted in the lOOmL saline. This solution was then filtered through a 0.22 micron filter for sterilization, resulting in a solution containing 21.25mcg of dipyridamole per mL. Using a dropper, one drop (equivalent to approximately 0.05mL) was applied to the eye.
EXEMPLARY FORMULATON D: Dipyridamole eye drops were prepared as follows lg of citric acid was mixed in lOOmL saline (0.9% w/v sodium chloride in sterile water) to obtain a pH of 7.7. 1.0625mg of dipyridamole was weighed, irradiated by UVB for 30 minutes for sterility, and diluted in the lOOmL saline. This solution was then filtered through a 0.22 micron filter for sterilization, resulting in a solution containing 10.625mcg of dipyridamole per mL. Using a dropper, one drop (equivalent to approximately 0.05mL) was applied to the eye. to RESULTS: Five human males suffering from GvHD-related dry eye were treated with one drop of Formulation A bilaterally twice daily. Subjective relief from the dry-eye symptoms was attained within half an hour. The patients required subsequent application twice daily. After 3 days of use, redness in the eye (or pink eye) disappeared.
Two human females suffering from diabetes-related dry eye were treated with one drop of Formulation C bilaterally twice daily. Relief from the dry-eye symptoms was attained within an hour. The patients required subsequent application twice daily. After 5 days of use, redness in the eye (or pink eye) disappeared.
A human female suffering from diabetes-related dry eye was treated with one drop of Formulation B bilaterally once every other day. Relief from the dry-eye symptoms was attained within twenty minutes. The patient required subsequent application once every other day. After 10 days of use, redness in the eye (or pink eye) disappeared. Maintenance continued with administration once every other day.
A human male suffering from a viral eye infection with comeal ulcer was treated with one drop of Formulation B bilaterally twice daily. Exudation ceased within 8 hours. The patient required subsequent application twice daily. After 4 days of use, redness in the eye (or pink eye) disappeared, and the eye was completely healed within 5 days.
A human male suffering in one eye from pterygium, with related dry eye and pink eye, was treated with one drop of Formulation B twice daily. Relief from the dry-eye symptoms was attained within one day. The patient required subsequent application twice daily. After 10 days of use, redness in the eye (or pink eye) it disappeared. After 6 weeks of use, the ptyregium shrank by about half its size, and continued to decrease in size with ongoing use.
A human female suffering in one eye from pterygium, with related dry eye and inflammation, was treated with one drop of Formulation C twice daily. Relief from the dry-eye symptoms was attained within two days. The patient required subsequent application twice daily. After 8 weeks of use, the ptyregium shrank by about half its size, and continued to decrease in size with ongoing use.
A human male suffering from a deep comeal ulcer with stromal involvement in one eye was treated with one drop of Formulation A three times daily. Relief from pain and irritation was attained within 24 hours. The patient required subsequent application twice daily. After 7 days of use, the cornea had completely re-epithelialized.
Three females suffering from diabetes-related comeal anesthesia (neurotrophic keratopathy) were treated with one drop of Formulation C daily. Symptoms of comeal anesthesia began improving within 2-3 days. The patients required subsequent application twice daily. After about 3 weeks of use, the patients reported complete relief of symptoms.
One male suffering from diabetes-related neovascularization was treated with one drop of Formulation A twice daily. When examined after 4 weeks of use, the abnormal vessels were no longer visible by slit-lamp examination.
Two human males suffering from a viral eye infection with comeal abrasion (i.e., the onset of a comeal ulcer) were treated with one drop of Formulation A bilaterally twice daily. Exudation ceased within 5 hours. The patients required subsequent application twice daily. After 2-3 days of use, redness in the eye (or pink eye) disappeared, and the eyes were completely healed within 5-6 days.
A human female suffering from a comeal ulcer in one eye was treated with one drop of Formulation A twice daily. Relief from pain and irritation was attained within one day. The patients required subsequent application twice daily. After 7 days of use, the ulcer had healed completely.
Four human males suffering from diabetes-related dry eye were treated with one drop of Formulation A bilaterally twice daily. Relief from the dry-eye symptoms was attained on average within half an hour. The patients required subsequent application twice daily. After an average of one week of use, redness in the eye (or pink eye) completely disappeared.
Two females suffering from diabetes-related comeal anesthesia were treated with one drop of Formulation A daily. Symptoms of comeal anesthesia started improving within 2 days. After approximately one week of use, the patients reported complete relief of symptoms.
A human male suffering from diabetes-related neovascularization was treated with one drop of Formulation C twice daily. The patient required subsequent application twice daily. When examined after 16 days of use, the abnormal vessels were no longer visible by slit-lamp photography examination.
Six human patients suffering from GvHD-related dry eye were treated with one drop of Formulation C bilaterally twice daily. Relief from the dry-eye symptoms was attained within one hour. The patients required subsequent application twice daily. After an average of one week of use, redness in the eye (or pink eye) disappeared.
A human male suffering from anterior uveitis in both eyes was treated with one drop of Formulation C three times daily. Relief from pain was attained within three days. Blurred vision was resolved within 7 days. Inflammation appeared to be
Priority Applications (21)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL225179A IL225179A (en) | 2013-03-12 | 2013-03-12 | Compositions for use in treating eye disorders using dipyridamole |
EP14764673.1A EP2968328A4 (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
CA2905594A CA2905594A1 (en) | 2013-03-12 | 2014-03-11 | 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 |
KR1020157027571A KR20150126021A (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
KR1020217001495A KR20210010638A (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
MYPI2015002196A MY182591A (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
EA201591653A EA035966B1 (en) | 2013-03-12 | 2014-03-11 | Use of a pharmaceutical composition for topical application in treating lacrimal system and anterior segment of the eye disorders |
SG11201507092QA SG11201507092QA (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
AU2014229371A AU2014229371B2 (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole |
SG10201706937UA SG10201706937UA (en) | 2013-03-12 | 2014-03-11 | Compositions for Use in Treating Eye Disorders Using Dipyridamole |
CN201480016302.6A CN105188702B (en) | 2013-03-12 | 2014-03-11 | Using Dipyridamole for treating the composition of disease of eye |
MX2015012716A MX2015012716A (en) | 2013-03-12 | 2014-03-11 | Compositions for use in treating eye disorders using dipyridamole. |
JP2015562486A JP6820658B2 (en) | 2013-03-12 | 2014-03-11 | Compositions for use in the treatment of eye diseases with dipyridamole |
BR112015022084A BR112015022084A2 (en) | 2013-03-12 | 2014-03-11 | compositions for use in treating eye disorders with the use of dipyridamole |
US14/483,181 US20150031712A1 (en) | 2013-03-12 | 2014-09-11 | Therapeutic Compositions Containing Dipyridamole and Treatment Packs Including Such Compositions and Methods for Producing Same |
CL2015002627A CL2015002627A1 (en) | 2013-03-12 | 2015-09-11 | Compositions for use in the treatment of eye disorders using dipyridamole |
US15/428,709 US9901580B2 (en) | 2013-03-12 | 2017-02-09 | Methods of eye treatment using therapeutic compositions containing dipyridamole |
US15/826,725 US10226420B2 (en) | 2013-03-12 | 2017-11-30 | Methods of eye treatment using therapeutic compositions containing dipyridamole |
US16/236,525 US10357453B2 (en) | 2013-03-12 | 2018-12-30 | Methods of eye treatment using therapeutic compositions containing dipyridamole |
US16/444,025 US10973758B2 (en) | 2013-03-12 | 2019-06-18 | Methods of eye treatment using therapeutic compositions containing dipyridamole |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL225179A IL225179A (en) | 2013-03-12 | 2013-03-12 | Compositions for use in treating eye disorders using dipyridamole |
Publications (2)
Publication Number | Publication Date |
---|---|
IL225179A0 IL225179A0 (en) | 2013-06-27 |
IL225179A true IL225179A (en) | 2017-01-31 |
Family
ID=48916407
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL225179A IL225179A (en) | 2013-03-12 | 2013-03-12 | Compositions for use in treating eye disorders 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) | SG10201706937UA (en) |
WO (1) | WO2014141079A1 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107106541A (en) * | 2015-01-28 | 2017-08-29 | 瑞采生技有限公司 | Compound and its medical application for strengthening PPAR γ performances and nuclear translocation |
US20180092776A1 (en) | 2016-09-30 | 2018-04-05 | Sara Heikali | Method and device for treating and managing diseased ocular tissue |
WO2021001806A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations with reduced impurities |
WO2021001805A1 (en) | 2019-07-04 | 2021-01-07 | Ocular Discovery Ltd. | Stable dipyridamole formulations and their methods of preparation |
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 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07258084A (en) * | 1994-03-17 | 1995-10-09 | Rohto Pharmaceut Co Ltd | Intracular pressure-reducing agent containing dipyridamole as essential component |
US5780450A (en) * | 1995-11-21 | 1998-07-14 | Alcon Laboratories, Inc. | Use of adenosine uptake inhibitors for treating retinal or optic nerve head damage |
US20060104968A1 (en) * | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
ZA200804550B (en) * | 2005-11-09 | 2009-08-26 | Combinatorx Inc | Methods, compositions, and kits for the treatment of medical conditions |
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 WO PCT/IB2014/059645 patent/WO2014141079A1/en active Application Filing
- 2014-03-11 JP JP2015562486A patent/JP6820658B2/en not_active Expired - Fee Related
- 2014-03-11 KR KR1020157027571A patent/KR20150126021A/en not_active IP Right Cessation
- 2014-03-11 CN CN201480016302.6A patent/CN105188702B/en not_active Expired - Fee Related
- 2014-03-11 MY MYPI2015002196A patent/MY182591A/en unknown
- 2014-03-11 SG SG10201706937UA patent/SG10201706937UA/en unknown
- 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 MX MX2015012716A patent/MX2015012716A/en unknown
- 2014-03-11 CA CA2905594A patent/CA2905594A1/en not_active Abandoned
- 2014-03-11 SG SG11201507092QA patent/SG11201507092QA/en unknown
- 2014-03-11 EA EA201591653A patent/EA035966B1/en unknown
- 2014-03-11 AU AU2014229371A patent/AU2014229371B2/en not_active Ceased
- 2014-03-11 EP EP14764673.1A patent/EP2968328A4/en not_active Withdrawn
-
2015
- 2015-09-11 CL CL2015002627A patent/CL2015002627A1/en unknown
Also Published As
Publication number | Publication date |
---|---|
CN105188702A (en) | 2015-12-23 |
CN105188702B (en) | 2019-03-26 |
WO2014141079A1 (en) | 2014-09-18 |
AU2014229371A1 (en) | 2015-10-29 |
EA035966B1 (en) | 2020-09-07 |
EA201591653A1 (en) | 2017-05-31 |
AU2014229371B2 (en) | 2018-05-10 |
JP2016514123A (en) | 2016-05-19 |
IL225179A0 (en) | 2013-06-27 |
EP2968328A1 (en) | 2016-01-20 |
SG11201507092QA (en) | 2015-10-29 |
CL2015002627A1 (en) | 2016-03-11 |
EP2968328A4 (en) | 2016-11-23 |
KR20210010638A (en) | 2021-01-27 |
BR112015022084A2 (en) | 2017-07-18 |
JP6820658B2 (en) | 2021-01-27 |
MX2015012716A (en) | 2016-07-06 |
MY182591A (en) | 2021-01-26 |
CA2905594A1 (en) | 2014-09-18 |
SG10201706937UA (en) | 2017-09-28 |
KR20150126021A (en) | 2015-11-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1753683B (en) | Ophthalmic formulation for the prevention and treatment of ocular conditions | |
US10973758B2 (en) | Methods of eye treatment using therapeutic compositions containing dipyridamole | |
KR20100067684A (en) | Water-immiscible materials as vehicles for drug delivery | |
AU2014229371B2 (en) | Compositions for use in treating eye disorders using dipyridamole | |
JP2011502989A (en) | Non-aqueous water-miscible materials as vehicles for drug delivery | |
WO2020252061A1 (en) | Carabachol-bromonidine formulation to enhance anti-presbyopia effects | |
KR101816277B1 (en) | Composition for treatment of corneal damage containing 7,8-dihydro-8-oxo-2'-deoxyguanosine or pharmaceutically acceptable salts thereof as an active ingredient | |
US9254289B2 (en) | Methods for treating eye disorders using dipyridamole | |
RU2485939C1 (en) | Disulfiram and taurine-containing ophthalmological medication in form of eye drops | |
RU2662364C2 (en) | Method for cataract treatment and eye drops for implementation thereof | |
CN116981457A (en) | Low concentration doses of synergistic ophthalmic compositions effective in preventing, controlling and eradicating presbyopia | |
WO2024193256A1 (en) | Use of beauvericin in preparation of drug for inhibiting angiogenesis | |
EP4364722A1 (en) | Pharmaceutical composition for preventing or treating diabetic eye disease comprising sglt-2 inhibitor | |
JP7197112B2 (en) | Pharmaceutical composition for treating bullous keratopathy | |
Kumar et al. | Comparative efficacy of gel-forming and ophthalmic solutions of 0.5% timolol in open-angle glaucoma | |
US20140213605A1 (en) | Methods for treating eye disorders using opioid receptor antagonists |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FF | Patent granted | ||
KB | Patent renewed |