EP4577190A1 - Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant - Google Patents

Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant

Info

Publication number
EP4577190A1
EP4577190A1 EP23769029.2A EP23769029A EP4577190A1 EP 4577190 A1 EP4577190 A1 EP 4577190A1 EP 23769029 A EP23769029 A EP 23769029A EP 4577190 A1 EP4577190 A1 EP 4577190A1
Authority
EP
European Patent Office
Prior art keywords
antioxidant
containing formulation
concentration
formulation
glutathione
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23769029.2A
Other languages
German (de)
English (en)
Inventor
Catherine J. Pachuk
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Marizyme Inc
Original Assignee
Marizyme Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Marizyme Inc filed Critical Marizyme Inc
Publication of EP4577190A1 publication Critical patent/EP4577190A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • 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

Definitions

  • Antioxidant-containing eye drop formulations to protect eyes against oxidative damage and/or stress, maintain and support general eye health, and methods of preventing and/or treating oxidative damage and/or stress in the eye using the antioxidant-containing eye drop formulations.
  • the eye drops are also ionically balanced and isotonic.
  • Eyes are very susceptible to oxidative damage and/or stress. Oxidative damage and/or stress is involved in the pathogenesis of many eye diseases, especially those that occur in the aging population. Examples of eye diseases arising from oxidative damage and/or stress include cataract, macular degeneration, uveitis, retinopathy, keratitis, ocular inflammation, dry eye disease, glaucoma, eye infection, and the like, but are not limited thereto.
  • the global eye health supplements market size was valued at USD 1.5 billion in 2019 and is expected to expand at a compound annual growth rate (CAGR) of 6.1% from 2020 to 2027.
  • CAGR compound annual growth rate
  • High myopia can be attributable to increased risk of various progressive eye disorders such as cataract, macular degeneration, uveitis, retinopathy, keratitis, ocular inflammation, dry eye disease, glaucoma, and the like, all of which are considered diseases of oxidative damage.
  • Increasing preference for eye health supplements among the older group of individuals and millennials highly prone to digital eye fatigue and myopia is further driving the market worldwide.
  • Increase in prevalence of various eye conditions including Age-related Macular Degeneration (AMD), dry eye syndrome, cataract, and inflammation along with the growing recommendation for eye health supplements by ophthalmologists for prevention and treatment of these disorders is also a contributing factor for the growth of this market.
  • AMD Age-related Macular Degeneration
  • the invention described in this application addresses a critical need in the market by formulating a stable, antioxidant-containing eye drop formulation to protect eyes against oxidative damage and/or stress.
  • An exemplary embodiment of the invention is directed to an aqueous antioxidantcontaining formulation, comprising: at least one antioxidant selected from the group consisting of L-ascorbic acid, L-glutathione, vitamin C, vitamin E, zinc, selenium and carotenoids, such as beta-carotene, lycopene, lutein, and zeaxanthin, a physiologically acceptable salt solution, and water.
  • at least one antioxidant selected from the group consisting of L-ascorbic acid, L-glutathione, vitamin C, vitamin E, zinc, selenium and carotenoids, such as beta-carotene, lycopene, lutein, and zeaxanthin, a physiologically acceptable salt solution, and water.
  • a concentration of the antioxidant is about 0.1 mM to about 200 mM.
  • the aqueous antioxidant-containing formulation comprises L-ascorbic acid; and a concentration of the L-ascorbic acid can be about 0.1 mM to about 5 mM, preferably about 1.0 mM or about 2.5 mM.
  • the aqueous antioxidant-containing formulation comprises L-glutathione; and a concentration of the L-glutathione can be about 0.1 mM to about 100 mM, preferably about 1.0 mM to about 20.0 mM.
  • the aqueous antioxidant-containing formulation comprises L-ascorbic acid and L-glutathione.
  • the physiologically acceptable salt solution comprises: calcium chloride, potassium chloride, magnesium sulfate, magnesium chloride, sodium chloride, sodium bicarbonate and sodium phosphate; and the physiologically acceptable salt solution can comprise: about 0.01 mM to about 25 mM calcium chloride; about 0.01 mM to about 150 mM potassium chloride; about 0.01 mM to about 20 mM monobasic potassium phosphate; about 0.01 mM to about 25 mM magnesium sulfate; about 0.01 mM to about 25 mM magnesium chloride; about 1 mM to about 175 mM sodium chloride; about 0.01 mM to about 30 mM sodium bicarbonate; and about 0.01 mM to about 25 mM dibasic sodium phosphate.
  • Any hydration form of the salts comprised in the physiologically acceptable salt solution can be used in certain embodiments of the formulation.
  • the antioxidant and the physiologically acceptable salt solution are kept separate prior to use and then mixed at point of use to create the eye drop formulation that is administered to the eyes.
  • the eye drop formulation is a single solution with all components in the single formulation.
  • the formulation can be packaged in one or more of the following formats: 1) Solution A (buffered salt solution), Solution B (L-glutathione + L-ascorbic acid), and Solutions A and B are combined at the time of use; 2) Solution A (potassium phosphate monobasic + sodium phosphate, dibasic anhydrous), Solution B (L-glutathione + L-ascorbic acid + all other salts), and Solutions A and B are combined at the time of use; 3) Solution A (potassium phosphate monobasic + sodium phosphate, dibasic anhydrous + some salts), Solution B (L-glutathione + L-ascorbic acid + other salts), and Solutions A and B are combined at the time of use; or 4) Solution A (potassium phosphate monobasic + sodium phosphate, dibasic anhydrous + salts proportionality distributed), Solution B (L-glutathione + L-ascorbic acid + salts proportionality distributed), and solutions A
  • Another exemplary embodiment of this invention is directed to a single- or multi-dosage form comprising the aqueous antioxidant-containing formulation.
  • Another exemplary embodiment of this invention is directed to a kit containing the single- or multi-dosage form comprising the aqueous antioxidant-containing formulation.
  • the kit can contain a single-dosage form comprising the aqueous antioxidant-containing formulation, and instructions for use, or a multi-dosage form comprising the aqueous antioxidant-containing formulation, and instructions for use.
  • Another exemplary embodiment of this invention is directed to a method for preparing an aqueous antioxidant-containing formulation, comprising: mixing at least one antioxidant selected from the group consisting of L-ascorbic acid, L-glutathione, vitamin C, vitamin E, zinc, selenium, and carotenoids, such as beta-carotene, lycopene, lutein, and zeaxanthin, and a physiologically acceptable salt solution with water, and mixing as required, to prepare a mixed formulation; and adding a pH adjusting agent to the mixed formulation, if needed, such that the mixed formulation has a pH of about 2.5 to about 5.5. For lower pH formulations (less than pH 4.5), a formulation that is not buffered or has low buffering capacity is optimal.
  • at least one antioxidant selected from the group consisting of L-ascorbic acid, L-glutathione, vitamin C, vitamin E, zinc, selenium, and carotenoids, such as beta-carotene, lycopene, lutein, and
  • the antioxidants can be selected from L-glutathione (and/or derivative cysteinylglycine), L-ascorbic acid, vitamin C, vitamin E, zinc, selenium and carotenoids and combinations thereof, but are not limited thereto.
  • Any suitable carotenoid can be selected from beta-carotene, lycopene, lutein, and zeaxanthin, but is not limited thereto.
  • antioxidants in an eye drop solution are: 1) to prevent and/or treat oxidative damage to ocular cell membranes and extracellular matrix structures; and 2) to stabilize other components of the solution by preventing oxidation, thereby improving the stability and shelf life of the product.
  • the concentration of the antioxidant is not limited hereto, and can include any values within any of the recited ranges and/or combinations thereof.
  • the aqueous antioxidant-containing formulation comprises L-ascorbic acid; and a concentration of the L-ascorbic acid can be about 0.1 mM to about 5 mM, about 0.2 mM to about 4.5 mM, about 0.5 mM to about 4 mM, about 1 mM to about 3.5 mM, about 1.5 mM to about 3 mM, about 2 mM to about 2.5 mM, preferably about 1.0 mM or about 2.5 mM.
  • the concentration of the L-ascorbic acid is not limited hereto, and can include any values within any of the recited ranges and/or combinations thereof.
  • the concentration of the L-glutathione is not limited hereto, and can include any values within any of the recited ranges and/or combinations thereof.
  • the physiologically acceptable salt solution can comprise any combination of salts known in the art that results in a physiologically acceptable salt solution.
  • the physiologically acceptable salt solution can include a combination of salts selected from among calcium chloride, magnesium chloride, potassium chloride, sodium chloride, sodium bicarbonate, potassium phosphate, sodium phosphate, and magnesium sulfate.
  • the amounts of the salts can vary over a large range depending on what combination of salts are used to prepare the physiologically acceptable salt solution.
  • Exemplary concentration ranges for the salts that can be used in the physiologically acceptable salt solution can include about 0.01 mM to about 25 mM calcium chloride, about 0.01 mM to about 150 mM potassium chloride, about 0.01 mM to about 20 mM monobasic potassium phosphate, about 0.01 mM to about 25 mM magnesium sulfate, about 0.01 mM to about 25 mM magnesium chloride, about 1 mM to about 175 mM sodium chloride, about 0.01 mM to about 30 mM sodium bicarbonate, and about 0.01 mM to about 25 mM dibasic sodium phosphate.
  • the physiologically acceptable salt solution can include about 0.01 mM to about 10 mM calcium chloride; about 0.01 mM to about 100 mM potassium chloride; about 0.01 mM to about 10 mM monobasic potassium phosphate; about 0.01 mM to about 10 mM magnesium sulfate; about 0.01 mM to about 10 mM magnesium chloride; about 1 mM to about 155 mM sodium chloride; about 0.01 mM to about 25 mM sodium bicarbonate; and about 0.01 mM to about 10 mM dibasic sodium phosphate. If salts exist in various hydration forms, any hydration form of the salt(s) can be considered for the eye drop formulation.
  • the concentration of the calcium chloride can be about 0.01 mM to about 25 mM, about 0.05 mM to about 15 mM, about 0.1 mM to about 10 mM, about 0.2 mM to about 7.5 mM, about 0.3 mM to about 5 mM, about 0.4 mM to about 2.5 mM, about 0.01 to about 1.0 mM, and the like.
  • the concentration of the potassium chloride can be about 0.01 mM to about 150 mM, about 0.05 mM to about 100 mM, about 0.1 mM to about 0.3 mM, about 75 mM, and the like.
  • the concentration of the potassium phosphate can be about 0.01 mM to about 20 mM, about 0.02 mM to about 15 mM, about 0.03 mM to about 10 mM, about 0.04 mM to about 7.5 mM, about 0.05 mM to about 5 mM, about 0.1 mM to about 2.5 mM, about 0.2 mM to about 1 mM, and the like.
  • the concentration of the magnesium sulfate can be about 0.01 mM to about 25 mM, about
  • the concentration of magnesium chloride can be about 0.01 mM to about 25 mM, about 0.02 mM to about 15 mM, about 0.03 mM to about 10 mM, about 0.04 mM to about 5 mM, about 0.05 mM to about 2.5 mM, about 0.1 mM to about 1 mM, and the like.
  • the concentration of magnesium chloride can be about 0.01 mM to about 25 mM, about 0.02 mM to about 15 mM, about 0.03 mM to about 10 mM, about 0.04 mM to about 5 mM, about 0.05 mM to about 2.5 mM, about 0.1 mM to about 1 mM, about 0.2 mM to about 0.5 mM, and the like.
  • the concentration of the sodium chloride can be about 0.10 mM to about 175 mM, 0.5 mM to about 150 mM, about 0.1 mM to about 125 mM, about 0.2 mM to about 120 mM, about 0.5 mM to about 100 mM, about 1 mM to about 75 mM, about 2 mM to about 50 mM, about 3 mM to about 25 mM, about 4 mM to about 15 mM, and the like.
  • the concentration of sodium bicarbonate can be about 0.01 mM to about 30 mM, about 0.05 mM to about 25 mM, about 0.1 mM to about 15 mM, about 0.2 mM to about 10 mM, about 0.3 mM to about 5 mM, about 0.1 mM to about 1 mM, and the like.
  • the concentration of the sodium phosphate can be about 0.01 mM to about 25 mM, about 0.02 mM to about 15 mM, about 0.03 mM to about 10 mM, about 0.04 mM to about 5 mM, about 0.05 mM to about 2.5 mM, about 0.01 mM to about 1.0 mM, and the like.
  • the concentrations of the various components are not limited hereto, and can include any values within any of the recited ranges and/or combinations thereof.
  • Exemplary aqueous antioxidant-containing formulations are described herein, and other exemplary formulations can independently include hydrated or anhydrous forms of the various components, and/or can exclude one or more components.
  • a pH of the aqueous antioxidant-containing formulation is about 2 to about 6, about 2.5 to about 5.5, about 3.0 to about 5.0, about 3.5 to about 4.5, about 3.5, about 4.0, about 5.0, and the like.
  • the pH values are not limited hereto, and can include any values within any of the recited ranges and/or combinations thereof.
  • the aqueous antioxidant-containing formulations described herein can include one or more adjuvants, such as preservatives, rheology modifiers, surfactants, humectants, phospholipids, and stabilizers, as long as they do not negatively impact the antioxidant activity of the formulation.
  • a rheology modifier can be included to change the viscosity of the final formulation.
  • exemplary rheology modifiers include carboxymethyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium hyaluronate, hyaluronic acid, a vinyl polymer compound, polyvinyl alcohol, polyvidone, poloxamer, a polyethylene glycol, a dextran, chondroitin sulfate, and alginic acid and salts thereof such as sodium alginate.
  • Exemplary humectants include glycerin, ethylene glycol, 1,3-butylene glycol, and propylene glycol.
  • An exemplary phospholipid is a lecithin.
  • Other phospholipids well known to those of skill in the art as useful in ophthalmic compositions are further contemplated as useful in the present compositions.
  • the amount of adjuvant that can be included in the formulation can be from about 0.01 wt% to about 5 wt%, based on the total weight of the formulation.
  • Another exemplary embodiment of this invention is directed to a method of preventing and/or treating ocular oxidative damage and/or stress, comprising: administering the aqueous antioxidant-containing formulation to an eye of a patient in need thereof.
  • the aqueous antioxidant-containing formulation can be dispensed into one or both eyes of a subject by any method known in the art.
  • the formulation can be dispensed into the eye as a drop that falls by gravity from a dispenser into the eye, as a spray, or by a mechanical mechanism, but is not limited thereto.
  • Each drop can have a specified volume.
  • a drop or dosage can deliver from about 10 pL to about 250 pL or any other desired volume.
  • the dosage can be about 20 pL to about 200 pL, or about 50 pL to about 150 pL, per eye per application.
  • installation of 1-2 drops per each eye, preferably one drop per eye can be administered about 1 to about 7 times a day.
  • about 1 drop of the formulation can be dispensed into one or both eyes once a day, or twice a day, or about 1 to about 4 times a day.
  • about 1 drop of the formulation can be dispensed into one or both eyes in the morning and about 1 drop of the formulation can be dispensed into one or both eyes in the evening.
  • about 1 drop of the formulation can be dispensed into one or both eyes before bed.
  • the formulation can be administered throughout the day on an as needed basis to alleviate a condition that is perceived by the user.
  • the aqueous antioxidant-containing formulation provided herein can be administered to any subject in need thereof.
  • the subject is a mammal.
  • the mammal can be a human, a cat, a dog, a rabbit, a bovine, an equine, an ovine, or a porcine, but is not limited thereto.
  • the formulations described in this application can be packaged as a unit dose in a blowfill-seal vial or an ophthalmic drug dispenser such as a simple squeeze bottle, but the container is not limited thereto.
  • the formulation can be delivered in an integral plastic bottle.
  • the bottle can be designed for application by squeezing the container.
  • the dispensing bottle can be a hand held pliable container that includes a cone-shaped nozzle, and the amount of formulation contained within the dispensing bottle that is dispensed can be adjusted by varying an inner diameter of the nozzle.
  • instillation into the eye includes inverting the dispensing bottle and squeezing it, which causes a drop to be dispensed.
  • the drop falls by gravity into the eye.
  • the size of the drop can depend on the rheology and surface tension of the solution, as well as the design and diameter of the nozzle diameter.
  • the dispenser can be designed so that the volume dispensed is independent of tilt angle of the dispensing bottle.
  • the formulation can be provided in a single-use container that is sterile until opened by the user, so that it does not need to have a preservative, and the container is disposed of after instilling the formulation into the eye.
  • the single-use container can be provided as a single use, blow molded, plastic vial, which can include a closure or can be a twist-off vial. Any consumer-friendly packaging can be used to store and administer the formulations.
  • the formulation can also be packaged as kits including a single dose or multiple doses.
  • the packaging can be aseptically packaged having a Sterility Assurance Level (SAL) of about 10’ 3 .
  • SAL Sterility Assurance Level
  • the formulation described in this application can be stored at temperature of up to about 32 °C, with a shelf life of at least one year at room temperature.
  • the analytical assay method for stability testing of total thiols and ascorbic acid in eyedrop formulations are performed as follows. Ascorbic acid and glutathione (as total thiols) are assayed in eyedrop formulations using a spectrophotometric method. Both components are measured on one sample preparation. The method utilizes the wavelength programming feature of the spectrophotometer. A standard curve is generated simultaneously for each component. The slopes of each linear line are used to interpolate the concentration of each component in the sample preparation. By applying the appropriate dilution and conversion factors, the concentration of each component in the formulation can be calculated. Ascorbic acid absorbance is measured at 260 nm vs. a reagent blank. Total thiols are derivatized using a molar excess of DTNB and measuring the absorbance of the sample solution at 412 nm vs. a reagent blank.
  • ascorbic acid appeared to be more stable at the lower pH of 3.5 compared to pH 5.
  • ascorbic acid appears to be more stable at the lower pH of Example 1A compared to the higher pH of Example IB, and at the lower pH of Example 3 A compared to the higher pH of Example 3B.
  • the stability of ascorbic acid was maintained regardless of pH (Examples 2A, 2B, 4A and 4B). This was an unexpected property of the formulations of this application compared to the known stability trends for ascorbic acid. Another unexpected result of the formulations of this application was the destabilizing effect of higher molar ratios of ascorbic acid on glutathione.
  • Draize test is a standard acute ocular toxicity test, which provides a method for assessing the irritation potential of materials that come in contact with human eyes, including eye care products and drugs designed specifically for topical ophthalmic use.
  • the current Draize method involves the instillation of about 10 pL of a test liquid (or about 10 mg of a test solid) into the lower conjunctival cul-de-sac, followed by a saline rinse.
  • Observations of various criteria are taken at predefined intervals, for example, at about 1 hour, about 24 hours, about 48 hours, about 72 hours, about 7 days, and about 21 days after administration.
  • a slit-lamp examination can be added to allow better assessment of comeal lesions, and topical fluorescein can be applied to reveal any cornel ulceration.
  • Optical or ultrasonic pachymetry can also be implemented to measure the extent of corneal thickening.
  • the Draize test is usually performed in rabbits due to their large eyes, well-described anatomy, ease of handling, relatively low cost, and ready availability. Inventors of this application do not expect to observe any adverse effects in any of the test subjects after exposure to the aqueous antioxidant formulations described in this application. Inventors of this application also expect the antioxidant aqueous formulation of this application to be safe and tolerable when administered to a subject in need thereof, including but not limited to a mammalian subject.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (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)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une formulation aqueuse contenant un antioxydant, comprenant : au moins un antioxydant choisi parmi l'acide L-ascorbique, le L-glutathion, la cystéinylglycine, la vitamine C, la vitamine E, le zinc, le sélénium, le bêta-carotène, le lycopène, la lutéine et la zéaxanthine ; et une solution de sel physiologiquement acceptable. L'invention concerne également un procédé de prévention et/ou de traitement d'une lésion et/ou d'un stress oxydatif oculaire par administration de la formulation aqueuse contenant un antioxydant à un patient en ayant besoin.
EP23769029.2A 2022-08-26 2023-08-25 Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant Pending EP4577190A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263401486P 2022-08-26 2022-08-26
PCT/US2023/031113 WO2024044342A1 (fr) 2022-08-26 2023-08-25 Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant

Publications (1)

Publication Number Publication Date
EP4577190A1 true EP4577190A1 (fr) 2025-07-02

Family

ID=88020780

Family Applications (1)

Application Number Title Priority Date Filing Date
EP23769029.2A Pending EP4577190A1 (fr) 2022-08-26 2023-08-25 Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant

Country Status (2)

Country Link
EP (1) EP4577190A1 (fr)
WO (1) WO2024044342A1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4620979A (en) * 1985-08-02 1986-11-04 Schachar Ronald A Ophthalmological irrigating solution containing ascorbate
GB0404693D0 (en) * 2004-03-02 2004-04-07 Univ London Pharmaceutical preparations for the treatment of ocular surface and other disorders
US20060275278A1 (en) * 2005-06-02 2006-12-07 Choy Camus K M Method and ophthalmic formulation for eye protection or treatment
CN106420809B (zh) * 2016-08-31 2017-08-08 浙江济民制药股份有限公司 一种眼科手术灌注液

Also Published As

Publication number Publication date
WO2024044342A1 (fr) 2024-02-29

Similar Documents

Publication Publication Date Title
AU2007338210B2 (en) Gel useful for the delivery of ophthalmic drugs
TWI849355B (zh) 含阿托平之水性組成物及其用途
JPH054918A (ja) 安定な水性製剤
JP2026035663A (ja) 高分子量ヒアルロン酸の眼科用薬物輸送ビヒクルとしての使用
CN111888326A (zh) 羟甲唑啉组合物和用于治疗眼障碍的方法
BR112021000240A2 (pt) Composições oftálmicas que contêm uma prostamida que libera óxido nítrico
EP4577190A1 (fr) Formulations de gouttes oculaires contenant un antioxydant et procédés de prévention et/ou de traitement les utilisant
AU2021250825B2 (en) Ophthalmic formulation and its use
JP7723851B1 (ja) アトロピン含有水性医薬組成物
HK1135020A (en) Gel useful for the delivery of ophthalmic drugs
HK40003059A (en) Atropine-containing aqueous composition

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20250326

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC ME MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)