IL121647A - Pharmaceutical compositions for the treatment of ocular inflammation comprising dexamethasone palmitate - Google Patents
Pharmaceutical compositions for the treatment of ocular inflammation comprising dexamethasone palmitateInfo
- Publication number
- IL121647A IL121647A IL12164797A IL12164797A IL121647A IL 121647 A IL121647 A IL 121647A IL 12164797 A IL12164797 A IL 12164797A IL 12164797 A IL12164797 A IL 12164797A IL 121647 A IL121647 A IL 121647A
- Authority
- IL
- Israel
- Prior art keywords
- dexamethasone
- treatment
- oil
- ester
- composition
- Prior art date
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- 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
- A61P27/14—Decongestants or antiallergics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A pharmaceutical composition in the form of an oil-in-water type emulsion for the treatment of ocular inflammations, comprising as an active ingredient, an effective amount of a lipophilic ester of dexamethasone.
Description
T Dttvp o i»3ttn ,o»i» nip^i!i ina>\? mnpn Pharmaceutical compositions for the treatment of ocular inflammations comprising dexamethasone palmitate Pharmateam Development Ltd.
C. 107618 PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF OCULAR INFLAMMATIONS COMPRISING DEXAMETHASONE PALMITATE FIELD OF THE INVENTION The present invention provides a novel formulation for the treatment of ocular inflammations and its use.
BACKGROUND OF THE INVENTION In recent years, oil-in water type emulsions increase in importance as vehicles for delivery of hydrophobic drugs, for example the fat emulsion' described in EP 315079.
U.S. Patent 4,340,594 describes a parenterally administered fat emulsion containing a steroid having an anti-inflammatory activity, inter alia dexamethasone palmitate. The fat emulsions described therein are useful in the treatment of rheumatism, immunological hemolytic anemia, idiopathic thrombocytopenic purpura, Paget disease or in conjunction with kidney transplantation.
Dexamethasone palmitate works as a prodrug since it is hydro-lyzed in the body by esterases into its bioactive metabolite, dexamethasone. Nonetheless, dexamethasone palmitate has some advantages over conventional water-soluble dexamethasone compositions owing to its lipid content.
SUMMARY OF THE INVENTION The present invention is based on the new finding that fat emulsions containing dexamethasone palmitate as the active ingredient are useful in the treatment of ocular inflammations.
Thus, the present invention relates to a pharmaceutical composition in the form of an oil-in-water emulsion for the treatment of ocular - inflammations, comprising, as an active ingredient, an effective amount of a lipophilic ester of dexamethasone, e.g. dexamethasone palmitate.
DETAILED DESCRIPTION OF THE INVENTION Emulsion is a dispersion of one liquid in a second immiscible liquid. Since the majority of emulsions contain water as one of the phases, it is customary to classify emulsions7 into two types: the oil-in-water (O/W) type consisting of colloid particles dispersed in water, and the water-in-oil (W/O) type in which the phases are reversed. The continuous liquid is referred as the dispersion medium and the liquid which is in the form of particles is called the disperse phase.
In order to achieve a stable emulsion, a third component - an emulsifying agent, must be' present. In an O/W type emulsion for example, each colloid particle has an oily core and an external layer comprising the emulsifiers and the surface active substances. A commercially available fat emulsion which contains 10% soybean oil is Intralipid® (Pharmacia AB, Sweden).
Oil-in-water type emulsions, which thus comprise oil-based particles dispersed in an aqueous medium, are capable of incorporating into their oily core or into their interfacial film, various hydrophobic drugs, and accordingly have been proposed and used as pharmaceutical carriers of such drugs. The present invention relates to such an oil-in-water type emulsion comprising a lipophilic ester of dexamethasone, as the pharmaceutical active ingredient (namely the drug), for the treatment of ocular inflammations.
The emulsion typically comprises, in addition to the active ingredient, an oil component and another component, being an emulsifier and/or a surface active agent. In addition, the aqueous phase (dispersion medium) typically comprises an osmotic pressure regulating agent dissolved therein, for raising the osmotic pressure to physiological levels.
In the following, concentrations of the ingredients of the emulsion will be given as %, meaning weight of ingredient in hundred volume units of total composition (w/v).
The composition of the invention comprises an effective amount of a lipophilic ester of dexamethasone. The term "effective amount" should be understood as an amount sufficient to impart a therapeutic effect. Obviously, the effective amount in the composition depends on the dosage form, on the therapeutic regime (namely whether the composition is given once daily, twice daily, etc.), the age group of the patient, the severity of the inflammation, as well as on various other factors as known per se. The artisan will have no difficulties in determining, by routine and straightforward experimentation, as to what constitutes an effective amount in each case.
Typical examples of lipophilic esters of dexamethasone are esters of dexamethasone with fatty acids, typically such acids having chains of 6 to about 22_ carbon atoms. Particular examples of such fatty acid are palmitic acid, oleic acid, linoleic acid, stearic acid and others. A particularly preferred fatty acid is palmitic acid (namely the active agent is preferably dexamethasone palmitate). Dexamethasone palmitate may typically be included in the composition ranging between 0.05%, typically 0.1% and preferably 0.15% to 0.5%, typically 0.4% and preferably 0.3%.
The oil component is typically a vegetable oil. Examples of vegetable oils are oleic acid, linoleic acid, lauric acid, soybean oil, olive oil, sunflower oil, and others. Vegetable oil is typically included in a concen-tration range of about 5% to 30% (w/v).
Typical emulsifiers are phospholipids. Examples of phospholipids are phosphatidylcholin, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingomyelins. Phospholipids are preferably included in a concentration range of about 0.5%-10% (w/v), and particularly in a concentration range of 1-5%.
Typical examples of surfactants are polyalkylene glycols having an average molecular weight of 1,000 to 10,000, polyoxyalkylene copoly- mers having an average molecular weight of 1,000 to 10,000 and poly-oxyethylene fatty acid esters.
Examples of osmotic pressure regulators are sucrose or glycerine.
In addition to the above ingredients, the compositions of the inventions may comprise various preservation agents such as methyl, ethyl and butyl paraben, or antioxidants such as a-tocopherol and ascorbic acid.
The pharmaceutical composition of the invention is typically provided in a suitable dosage form, e.g. in the form of eye drops, with the concentration of the active ingredient being such so that a given amount of drops, e.g. 1-2 to be administered at each time.
The present invention also provides a method of treatment of ocular inflammations comprising topically applying to the eye an oil-in-water type emulsion, comprising a lipophilic ester of dexamethasone as the active ingredient.
Still further provided by the invention is use of a lipophilic ester of dexamethasone and an oil-in-water type emulsion, for the preparation of a topical ocular composition for the treatment of ocular inflammations.
The invention will be illustrated below, with reference to some non limiting examples. 1. EXPERIMENTAL PROCEDURES Animal Husbandry Fifteen (15) male NZW rabbits, supplied by a local breeder (Levinstein, Yokneam, Israel) and weighing 2.0-2.5 kg were used in the study.
The albino rabbit has been selected for this study, since it is widely acclaimed in reports published in the scientific literature, as a most suitable experimental model for the evaluation of newly developed and clinically applied agents for the therapy of anterior uveitis.
On arrival each animal was inspected and only suitable and healthy animals were expected for use. Animals were acclimated for 5 days following receipt during which they ware observed daily for signs of ill health. No abnormalities were detected.
Rabbits were kept within a limited access laboratory animal facility , at environmental conditions of a target temperature of 17 to 23°C, a target humidity of 30-70% and a 12-hour light/12-hour dark cycle. Temperature and relative humidity were recorded daily. No deviation from the target values were observed.
Rabbits were housed individually in stainless steel cages, mounted in batteries. The cages measured 50x45x48 cm and were fitted with perforated stainless steel floors over undertrays.
Animals were uniquely identified by ear number tattoo.
Each cage was outfitted with a cage card visible on the front and containing the study number, animal number, sex and strain of the animals and all relevant details regarding treatment.
A complete commercial pelleted rabbiLdiet (AMBAR 19701) was fed without restriction and the animals were allowed free access to water supplied via a cage-side water bottle. 2. TEST AND CONTROL COMPOSITIONS Test composition: a commercially available composition comprising an oil-in-water type emulsion containing dexamethasone palmitate at a concentration of 4 mg/ml (LIMETHASON™, Green Cross Corporation, Japan).
Reference composition: a commercially available clear aqueous ophthalmic solution, containing 1 mg ml dexamethasone disodium phosphate (STERODEX™, Fischer Pharmaceutical Labs. (1975) Ltd., Israel). 3. EXPERIMENTAL DESIGN CONDITIONS Allocation of Animals to Test Groups Animals were assigned to test groups, in a blinded fashion to prevent experimental bias on the part of the person conducting clinical and laboratory examinations. One group was treated with the Test composition, one with the Reference composition and the third group was an untreated control group. The code detailing the respective treatment a particular test animal was subjected to, was opened only upon termination of both clinical and laboratory examinations.
- Induction of Experimental Uveitis EIU was carried out_ in all animals of the three test groups by endotoxin lipopolysaccharide (LPS-E.coli), injected intravitreally at a dose of 2 μ (40 μ\ of 50 μ\ LPS/1 ml HPCD [hydroxypropyl cyclodextrin]) into the left eye of each test animal. Throughout the procedure, animals were anesthetized by intramuscular injection of Ketamin HCL 30 mg/kg and Xylazine HCL 5 mg/kg.
EIU Control - Contralateral (right) eyes served as controls for LPS-injected eyes, and were injected intravitreally in an identical fashion, using 50 μ\ of sterile saline. 4. TREATMENT Immediately following induction of experimental uveitis, rabbits of both the Test and Reference composition groups received the first of a total of six (6) repeated ocular instillations, by applying one drop of the respective preparations into both eyes- (LPS and Saline injected eyes). Subsequently, two further instillations were carried at a time interval of about 3 to 4 hours. On the next day and following the 24-hour clinical examination period (see below), the remaining three instillations were made in an identical fashion and at equally spaced time intervals. 5. OBSERVATIONS AND EXAMINATIONS Clinical Examination Clinical examination of the rabbits' eyes were carried out 24 and 48 hours following LPS injection and based on scoring of conjunctival inflammatory response, iridal hyperemia and anterior chamber flare, according to the detailed grading scale shown below: I. Grading Scale - Conjunctiva 0 = Normal. Vessels of the palpebral and bulbar conjunctiva easily observed. May appear blanched to reddish pink but without perilimbal injection. 1 = Flushed, reddish color predominantly confined to the palpebral conjunctiva with some perilimbal injection, primarily confined to upper and lower parts of eye. 2 = Bright red color of the palpebral conjunctiva with accompanying perilimbal injection covering at least 75% of the circumference of the perilimbal region. 3 = Dark, beefy red color with congestion of both bulbar and palpebral conjunctivae, along with pronounced perilimbal injection and the presence of petechia on the conjunctiva.
II. Grading Scale - Iris 0 = Normal. Iris without any hyperemia of iridal vessels. Occasionally, near the pupillary borders a small area of about 1-2 mm in diameter, slightly hyperemic secondary and tertiary vessels may be discerned. 1 = Minimal injection of secondary vessels (but not tertiary).
Generally uniform, but may be of greater intensity at 1 :00 or 6:00 o'clock positions. If visible intensive injection of vessels confined to that area, tertiary vessels are considered to be substantially hyperemic. 2 = Minimal injection of tertiary vessels and minimal to moderate injection of secondary vessels or iris stroma swelling alone. 3 = Moderate injection of secondary and tertiary vessels. In addition, slight swelling of iris stroma (most prominent near the 3:00 and 9:00 o'clock positions). 4 = Marked injection of the secondary and tertiary vessels with marked swelling of the iris stroma. Iris appears rugose and may be accompanied by hemorrhage in the anterior chamber.
III. Grading Scale - Anterior Chamber Flare. 0 = Normal. Complete absence of flare. 1 =_ Barely detectable, faint flare. - 2 = Moderate flare. Iris and lens detail clear. 3 = Marked iris flare. Iris and lens details hazy. 4 = Intense flare. Fixed coagulated aqueous humor with considerable fibrin.
The scores for all three clinical parameters, determined at each observation period, were separately totaled for each eye of individual animals. The scores for the 24 and 48 hour examination were added and served as "Cumulative Score ".
Aqueous Humor Differential Cell Count Following the 48-hours clinical evaluation of eyes.-animals were anesthetized (Ketamin HCL 100 mg/kg and Xylazine HCL 15 mg/kg by i.m. injection) and aqueous humor was sampled from both eyes of each test animal, using an appropriate hypodermic needle and syringe. Differential cell counts were determined using a hemocytometer.
Cell count values were expressed as the total number of different cell types examined (mononuclear and segmented leukocytes; erythrocytes; epithelial cells), in both eyes of individual animals.
Measurement of Protein Content in Aqueous Humor Immediately after collection of aqueous humor samples for cell count examination, the remaining aqueous humor was centrifuged for 5 minutes in MIKRO 12/24 centrifuge (Hettich Zentrifugen). The supernatant was then submitted to protein assay, using a standard commercial assay kit (BioRad Standard III). Protein content of aqueous humor was determined for both eyes of all test animals.
Preservation of Eyes for Histopathological Examination Following aqueous humor aspiration all test animals were sacrificed and their eye was enucleated and fixed in Davidson's solution. 6. RESULTS AND DISCUSSION The results of this study are presented in Fig. 1 -and in Table 1 below; Table 1 summarizes the data for all test groups, with respect to the evaluation criteria of clinical grading, aqueous humor protein content and cell count, for each of the three types of treatments.
Table 1: Summary of Mean Values ± SD for EIU Parameters Measured in the Left Eye (LPS-injected) of Rabbits Statistically significant difference from Untreated Control group using the Student t-test (p<0.05) Fig. 1 shows the same results presented in Table 1 in a more illustrated graphic form. In Fig. 1, the evaluation criteria of clinical grading, the aqueous humor protein content and the aqueous humor cell count, are shown in Graphs 1, 2 and 3, respectively. Each of the bars represented as A, B, C, D, E and F, show the mean and the standard deviation values, of the following: A, B - untreated control; A - LPS-injected left eye and B - saline-injected right eye.
C,D - animals treated with the reference composition;- C - LPS-injected left eye, D - saline-injected right eye.
E,F - animals treated with the test composition; E - LPS-injected left eye, F - saline-injected right eye.
The data pertaining to animals of the Untreated control test group clearly show the marked differences in experimental parameters between left (LPS-injected)-and right (saline-injected) eyes, reflecting the well known acute inflammatory reactions to intravitreal LPS injection in the EIU model. Thus, within 24 hours after the intravitreal injections, the left eyes of all animals of the group exhibited distinct clinical evidence of marked conjunctival and iridal congestion and anterior chamber flare and which practically remained the same at the time of the 48-hour inspection. In none of these animals, the right control eyes injected with intravitreal sterile saline showed evidence of inflammation at the two successive inspections.
Determinations of both aqueous protein content and cell count in untreated controls, confirmed the clinical observations. Particularly with respect to the former, there was a striking difference between the two contralateral eyes, shown by a mean protein concentration of about 130 mg/ml in LPS-injected (left) eyes as compared to the normal level of about 2-4 mg/ml in control (right) eyes. Judging by the data of total cell counts, and at least under the conditions of the study, this parameter seemingly was not as indicative and consistent a measure as that of protein content, towards assessing the extent of acute ocular inflammations.
Both the Test composition and the Reference Composition effectively reduced acute inflammatory response resulting from EIU evidenced in that it suppressed all three examined experimental criteria. Thus, with respect to the "Cumulative Score " for grading clinical signs, the relative effects of the two compositions in reducing inflammation in left (LPS-injected) eyes vs. corresponding eyes in the Untreated Control group were of statistical significance (p<.05). Similar statistically significant (p<.05) treatment effects was demonstrated by the reduction in the levels of aqueous humor protein concentration by both compositions.
Regarding the comparative treatment effectiveness of both compositions, an apparent consistent enhanced activity by the Test composition was observed in all of the examined experimental parameters. This relative increase was especially evident from the data pertaining to both the "Cumulative Score " of clinical grading and aqueous protein content. -In terms of percentage (%) differences, the Test composition treatment caused a reduction of about 70 and 50% in clinical severity and protein content, respectively, as compared to a corresponding reduction of about 55 and 35% following the Reference composition. This shows that optimal concentration of the dexamethasone palmitate may be lower than that in the Test composition, e.g. 0.2% or 3%.
Treatment applied to the right saline-injected control eyes, did not reveal any obvious treatment-related effects. 121647/2
Claims (8)
1. A pharmaceutical composition in the form of an oil-in-water type emulsion for the treatment of ocular inflammations, comprising as an active ingredient, an effective amount of a lipophilic ester of dexamethasone.
2. The pharmaceutical composition of Claim 1, wherein the active ingredient is an ester of dexamethasone with a fatty acid.
3. The pharmaceutical composition of Claim 2, wherein the ester of dexamethasone is dexamethasone palmitate.
4. The pharmaceutical composition of any one of Claims 1 to 3 in the form of eye drops.
5. Use of a lipophilic ester of dexamethasone and an oil-in-water type emulsion for the preparation of a topical eye composition for the treatment of ocular inflammation, substantially as described in the specification.
6. Use according to Claim 5, wherein the dexamethasone ester is dexamethasone palmitate.
7. A method of treatment of ocular inflammations comprising topically applying to the eye of a non-human mammal an oil-in-water type emulsion, comprising a lipophilic ester of dexamethasone as the active ingredient.
8. A method according to Claim 7, wherein the dexamethasone ester is dexamethasone palmitate. For the Applicants REINHOLD COHN AND PARTNERS
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL12164797A IL121647A (en) | 1997-08-28 | 1997-08-28 | Pharmaceutical compositions for the treatment of ocular inflammation comprising dexamethasone palmitate |
CA002300850A CA2300850A1 (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical compositions for the treatment of ocular inflammations comprising dexamethasone palmitate |
EP98940536A EP1009409A1 (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical compositions for the treatment of ocular inflammations comprising dexamethasone palmitate |
PCT/IL1998/000411 WO1999011270A1 (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical compositions for the treatment of ocular inflammations comprising dexamethasone palmitate |
AU88839/98A AU8883998A (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical compositions for the treatment of ocular inflammations comprisingdexamethasone palmitate |
CN98809486A CN1271288A (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical compositions for the treatment of ocular inflammations comprising dexamethasone palmitate |
JP2000508372A JP2001514228A (en) | 1997-08-28 | 1998-08-26 | Pharmaceutical composition for treating ocular inflammation containing dexamethasone palmitate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL12164797A IL121647A (en) | 1997-08-28 | 1997-08-28 | Pharmaceutical compositions for the treatment of ocular inflammation comprising dexamethasone palmitate |
Publications (2)
Publication Number | Publication Date |
---|---|
IL121647A0 IL121647A0 (en) | 1998-02-08 |
IL121647A true IL121647A (en) | 2001-07-24 |
Family
ID=11070569
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL12164797A IL121647A (en) | 1997-08-28 | 1997-08-28 | Pharmaceutical compositions for the treatment of ocular inflammation comprising dexamethasone palmitate |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1009409A1 (en) |
JP (1) | JP2001514228A (en) |
CN (1) | CN1271288A (en) |
AU (1) | AU8883998A (en) |
CA (1) | CA2300850A1 (en) |
IL (1) | IL121647A (en) |
WO (1) | WO1999011270A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4463681B2 (en) * | 2002-07-15 | 2010-05-19 | アルコン,インコーポレイテッド | Non-polymeric lipophilic pharmaceutical implant composition for intraocular use |
US7767217B2 (en) * | 2006-03-14 | 2010-08-03 | Foresight Biotherapeutics | Ophthalmic compositions comprising povidone-iodine |
DK1864668T3 (en) * | 2006-06-01 | 2013-03-04 | Novagali Pharma Sa | APPLICATION OF PRODRUG FOR OCULAR, INTRAVITREAL ADMINISTRATION |
KR101541416B1 (en) | 2006-06-01 | 2015-08-03 | 산텐 에스에이에스 | Use of a Steroid Prodrug for the Treatment of Disease of the Posterior Segment of the Eye |
EP2564853B1 (en) * | 2007-12-04 | 2019-02-27 | Santen SAS | Compositions comprising corticosteroid prodrug such as dexamethasone palmitate for the treatment of eye disorders |
CN108434090A (en) * | 2017-02-14 | 2018-08-24 | 高药品股份有限公司 | Using physiology fat as the steroids ointment of base |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS609726B2 (en) * | 1980-05-15 | 1985-03-12 | 株式会社 ミドリ十字 | steroid preparations |
JPS62270521A (en) * | 1986-05-16 | 1987-11-24 | Green Cross Corp:The | Flurbiprofen preparation for ophthalmic administration |
IL88076A (en) * | 1987-10-28 | 1993-01-14 | Nippon Shinyaku Co Ltd | Fat emulsions as drug carriers |
JPH05124965A (en) * | 1991-11-06 | 1993-05-21 | L T T Kenkyusho:Kk | Nasal and bronchial disease-therapeutic agent for local application |
-
1997
- 1997-08-28 IL IL12164797A patent/IL121647A/en not_active IP Right Cessation
-
1998
- 1998-08-26 CN CN98809486A patent/CN1271288A/en active Pending
- 1998-08-26 AU AU88839/98A patent/AU8883998A/en not_active Abandoned
- 1998-08-26 CA CA002300850A patent/CA2300850A1/en not_active Abandoned
- 1998-08-26 JP JP2000508372A patent/JP2001514228A/en active Pending
- 1998-08-26 EP EP98940536A patent/EP1009409A1/en not_active Ceased
- 1998-08-26 WO PCT/IL1998/000411 patent/WO1999011270A1/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
JP2001514228A (en) | 2001-09-11 |
WO1999011270A1 (en) | 1999-03-11 |
EP1009409A1 (en) | 2000-06-21 |
CA2300850A1 (en) | 1999-03-11 |
CN1271288A (en) | 2000-10-25 |
AU8883998A (en) | 1999-03-22 |
IL121647A0 (en) | 1998-02-08 |
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