[go: up one dir, main page]

WO2025210386A1 - Compositions pharmaceutiques pour colorer des membranes et d'autres structures biologiques à l'aide d'un colorant vital à base de cbd naturel ou synthétique isolé et/ou associé à d'autres colorants pour une chirurgie vitréo-rétinienne - Google Patents

Compositions pharmaceutiques pour colorer des membranes et d'autres structures biologiques à l'aide d'un colorant vital à base de cbd naturel ou synthétique isolé et/ou associé à d'autres colorants pour une chirurgie vitréo-rétinienne

Info

Publication number
WO2025210386A1
WO2025210386A1 PCT/IB2024/053301 IB2024053301W WO2025210386A1 WO 2025210386 A1 WO2025210386 A1 WO 2025210386A1 IB 2024053301 W IB2024053301 W IB 2024053301W WO 2025210386 A1 WO2025210386 A1 WO 2025210386A1
Authority
WO
WIPO (PCT)
Prior art keywords
staining
biological
pharmaceutical composition
membranes
dyes
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
PCT/IB2024/053301
Other languages
English (en)
Inventor
Diogo SOUSA-MARTINS
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.)
Vicadia Lda
Original Assignee
Vicadia Lda
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 Vicadia Lda filed Critical Vicadia Lda
Publication of WO2025210386A1 publication Critical patent/WO2025210386A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/006—Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0023—Di-or triarylmethane dye
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0033—Blends of pigments; Mixtured crystals; Solid solutions
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0071—Process features in the making of dyestuff preparations; Dehydrating agents; Dispersing agents; Dustfree compositions
    • C09B67/0083—Solutions of dyes
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A61K9/0051—Ocular inserts, ocular implants

Definitions

  • Dyes are chemical compounds that bind to various substances in nature to induce colour.
  • Vital dyes emerged recently as an important and effective surgical adjuvants to enhance visualization of biological membranes and structures, since these compounds have the ability to intravital and supravital dyeing or staining of living tissues or cells in a living organism and living cells or tissues freshly removed from the body.
  • Vital dyes have been used in cataract and vitreoretinal surgery, as well as in corneal, glaucoma, orbit, strabismus, and conjunctival surgery (Abrams et al., 1978; Dhaliwal et al., 2022; Farah et al., 2009; Rodrigues et al., 2009).
  • This technique represents one of the most efficient, objective, non-invasive, and directly visible means for biological membranes and structures identification, facilitating the delicate and precise manipulation and removal of fragile biological membranes and structures, which in most cases are thin and semi-transparent, with the required precision (Abrams et al., 1978; Aiello et al., 2020; Delyfer et al., 2020; Dhaliwal et al., 2022; Farah et al., 2009; Guber et al., 2019; Mantelli et al., 2013; Ribeiro et al., 2022; Rodrigues et al., 2009).
  • BurkS. etal. (Burk et al., 2000) first described this technique in 2000, by using the vital dye indocyanine green (ICG), which has a high affinity for the ILM.
  • ICG vital dye indocyanine green
  • This innovative method utilizes vital dyes to selectively stain specific structures within the eye, enhancing visualization and precision during surgical procedures, since the vitreous and retina exhibit a transparent and intricately layered nature and several studies have shown retinal complications caused by the inaccurate removal of these structures (Abrams et al., 1978; Dhaliwal etal., 2022; Farah et al., 2009; Rodrigues et al., 2009).
  • the TB provides a contrast between the stained capsule and the underlying lens, while crystalline steroid Triamcinolone Acetonide is the primary line I3)r vitreous identification and BBG shown to be best stains I3)r the ILM.
  • crystalline steroid Triamcinolone Acetonide is the primary line I3)r vitreous identification and BBG shown to be best stains I3)r the ILM.
  • recent studies shown that the use 00 vital dyes in biological membranes and structures dyeing or staining has been limited due to their low chemical aHBnity and lack 00 precise saGfety indicators presented during trials, therein re achieving optimal staining while avoiding adverse effects remains a challenge (Dhaliwal et al., 2022; Farah et al., 2009; Rodrigues et al., 2009).
  • TP and BBG are more effective Gbr optimal coloration, particularly at low concentrations, however, their delivery to membranes and structures is oGten compromised and less effective, resulting in insufficient contrast between the target intraocular membranes and the surrounding structures, which could complicate the surgical procedure.
  • natural or synthetic CBD-based vital dye is a potential solution Gbr stabilising these dyes in structures.
  • the pharmaceutically acceptable vehicles currently used could achieve the creation of larger molecules, being a carrier system that allows controlled release of the innovative formulation and have the potentialto improve effectiveness. Altering the molecularweight of an ocular dye will improve its adherence to retinal membranes during vitrectomy by utilizing the molecular sinking effect.
  • having the patient in a supine position (lying face up) during the dye delivery can also optimize dye contact with the ocular surface.
  • a higher viscosity formulation may address the issue of current dyes being too liquid for optimal adherence during surgery along the target-delivery provided by the natural or synthetic CBD-based vital dye isolated and/or associated with other dyes formulation.
  • the endocannabinoid system is an active and complex cell signalling system mediated by the endocannabinoids lipidic molecules such as endocannabinoids 2- arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide or AEA) that bind to the G protein-coupled cannabinoid receptors (CB1 R and CB2R) (Lu and Mackie, 2016; Schwitzer et al., 2016).
  • endocannabinoids lipidic molecules such as endocannabinoids 2- arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide or AEA) that bind to the G protein-coupled cannabinoid receptors (CB1 R and CB2R) (Lu and Mackie, 2016; Schwitzer et al., 2016).
  • CB1 R are primarily found in central nervous system (CNS), particularly in cortex, basal ganglia, hippocampus, and cerebellum, outnumbering many of the other receptor types on the brain
  • CB2R can also be observed in the peripheral organs especially is primarily present the immune tissues and playa key role in the immune functioning control and maintenance. Studies shown that it can also modulate intestinal inflammation, contraction, and pain in inflammatory bowel conditions (Bradshaw and Walker, 2005; Lu and Mackie, 2016; Schwitzer et al., 2016).
  • the ECS can act like a neuromodulatory system in the development CNS by influencing neuronal synaptic plasticity and transmission, and regulation of several physiological functions, for instance body temperature, movement and motor coordination, learning and memory, addictive- like behaviour and pain modulation, inflammatory and immune responses and other basic body needs such as cardiovascular function, sleep and visual processing by the optical nerve (Bradshaw and Walker, 2005; McCormick et al., 2019; Schwitzer et al., 2016),
  • the cannabinoid receptors are the primary target of exogenous cannabinoids, such as A-9-tetra- hydrocannabinol (THC) and cannabidiol (CBD) present in Cannabis, highly interact with the cannabinoid receptors CB1 R and CB2R (Saraiva et al., 2023).
  • cannabinoids such as A-9-tetra- hydrocannabinol (THC) and cannabidiol (CBD) present in Cannabis, highly interact with the cannabinoid receptors CB1 R and CB2R (Saraiva et al., 2023).
  • Cannabis sativa contains a wide range of bioactive compounds including phenols, flavonoids and anthraquinones.
  • the THC and CBD are the most studied ones, due to their therapeutic and biological properties and recent association with neuromodulatory systems when interacting with ECS leading to neuronal synaptic communication and affect biological functions (Zantut et al., 2020).
  • THC and CBD interact with the ECS, their molecular structures and functions within the ECS differ significantly. While, THC has a cyclic ring structure and a side chain with a phenol group (OH) and an alkene group, contributing to its ability to bind to CB1 R in the CNS; CBD has a similar cyclic structure but lacks the side chain found in THC being considered non-psychoactive.
  • CBD contains a phenol group (OH) associated with various therapeutic properties, including anti-inflammatory and anxiolytic effects, however the underlying biomolecular mechanisms still remain unclear (Ibeas Bih et al., 2015; Saraiva et al., 2023; Watkins, 2019; Zantut et al., 2020; Zhornitsky and Potvin, 2012).
  • OH phenol group
  • CBD has a low binding affinity for CB1 receptors, mainly interacting with CB2R, which are predominantly found in peripheral tissues and the immune system contributing to antiinflammatory and immunomodulatory process, but also found in the retinal glia, more specifically in the Muller cells (Borowska-Fielding et al., 2018; Bouskila et al., 2016).
  • CBD activates 5-HT1A serotonergic and TRPV1-2 vanilloid receptors, antagonizes alpha-1 adrenergic and p-opioid receptors(lbeas Bih et al., 2015; Zhornitsky and Potvin, 2012).
  • CBD has been shown to have analgesic (Petersen et al., 2023), anticonvulsant, muscle relaxant (Isenmann et al., 2021 ), neuroprotective (Fernandez- Ruiz et al., 2013), antioxidant (Atalay et al., 2019), and anti-psychotic activity (Waldo Zuardi et al., 2012).
  • CBD cannabidiol
  • CBD is one of at least 85 active cannabinoids identified within the Cannabis plant.
  • CBD has been shown to have analgesic (Petersen et al., 2023), anticonvulsant, muscle relaxant (Isenmann et al., 2021 ), neuroprotective(Fernandez-Ruiz et al., 2013), antioxidant (Atalay et al., 2019), and anti-psychotic activity (Waldo Zuardi et al., 2012).
  • CBD activates 5-HT1 A serotonergic and TRPV1-2 vanilloid receptors, antagonizes alpha-1 adrenergic and p-opioid receptors (Ibeas Bih etal., 2015; Zhornitsky and Potvin, 2012).
  • CBD is a colourless molecular, after degradation in the membrane cells, it may appear purple due to the increase in the concentration of the photochemically unstable oxidation product CBD-hydroxyquinone (HU-331 ). In the presence of oxygen, water and/or exposed to natural light/dark cycles, this hydroxyquinol rapidly reacts to form a multitude of violet/purple -coloured cannabinoid by-products (Thomson et al., 2023).
  • the present invention describes the use of a new technique to achieve the coloration of the ocular tissue using pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD-based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach in vitreoretinal surgery.
  • Those pharmaceutical compositions are to be used as a practice for dyeing or staining biological membranes and structures, in order to facilitate their identification and biomolecular membrane composition during surgical procedures such as vitreoretinal surgery, resulting in the visualization of different types of ocular membranes and tissues alongwith the cellularand tissue protection from damage induced by the exposition to surgical light.
  • the antioxidative and anti-inflammatory effects of a natural or synthetic CBD-based vital dye isolated and/or associated with other dyes will be also expected.
  • the ASA effect - Anti-inflammatory Sinking Antioxidant effect - could be an innovative pharmaceutical mechanism of action for the purposed stain, exhibiting antioxidative and anti-inflammatory properties.
  • This dye could be either naturally derived or synthetically produced and could be used alone or in combination with other dyes.
  • the present invention describes the use of a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach during surgical or medical procedures, such as vitreoretinal.
  • a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach during surgical or medical procedures, such as vitreoretinal.
  • the use of such compounds for the preparation of dyeing or staining compositions in order to facilitate their identification and biomolecular membrane composition results in the visualization of different types of ocular membranes and tissues along with the cellular and tissue protection from damage induced by the exposition to surgical light.
  • the present invention describes the entirety process, since the production of the composition purpose along with formulation and studies conducted, until the purport method for staining biological membranes and structures to improve their adequate identification and manipulation, responding to the challenged presented by the complexity of the surgical procedure mainly chromovitrectomy.
  • CBD has been shown to have analgesic(Petersen et al., 2023), anticonvulsant, muscle relaxant (Isenmann et al., 2021), neuroprotective (Fernandez-Ruiz et al., 2013), antioxidant (Atalay et al., 2019), and anti-psychotic activity (Waldo Zuardi et al., 2012).
  • CBD activates 5-HT1A serotonergic and TRPV1-2 vanilloid receptors, antagonizes alpha-1 adrenergic and p-opioid receptors (Ibeas Bih et al., 2015; Zhornitsky and Potvin, 2012).
  • the present invention introduces a novel technique for staining intraocular structures and membranes, aiming to enhance visualization, precision, and safety during surgical procedures.
  • This technique involves the use a natural or synthetic CBD-based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, to achieve optimal staining of the vitreous and retinal tissue.
  • compositions selectively stain the biological structure of interest, staining the target biological membranes and structures at a concentration that is physiologically and toxicologically acceptable, allowing for the use of the minimum concentration of dye that provides visible differentiation between the selected biological membranes and the surrounding. Despite the low or non-existent toxicity of these dyes, any remaining pharmaceutical composition in the surgical and medical field is promptly removed after the procedure, further reducing the possibility of post-process adverse effects.
  • the invention also offers a method for staining biological membranes and structures with these pharmaceutical compositions.
  • This method allows for the selective staining of the biological structure of interest, leavin the surroundingstructures undyed or less dyed. This leads to a more precise identification of the desired biological membranes and structures and facilitates its surgical manipulation or removal, reducing the risk of damaging the surrounding tissues and, consequently, reducing the recovery time.
  • the pharmaceutical compositions and methods described here can improve the contrast between different types of biological tissues during surgical or other procedures that require staining of biological material, along with the increased protection to tissues and cells from light damage in the surgical field.
  • the present invention allows for the protection of intraocular structures through topical application or injection of pharmaceutical compositions containing the natural substance a natural or synthetic CBD-based vital dye . This method poses a low risk of toxicity for the patient.
  • the present invention describes the use of a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach in surgery, such as vitreoretinal.
  • a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach in surgery, such as vitreoretinal.
  • Those pharmaceutical compositions are to be used as a practice for dyeing or staining biological membranes and structures in surgery, in order to facilitate their identification and biomolecular membrane composition during surgical procedures such as vitreoretinal surgery, resulting in the visualization of different types of ocular membranes and tissues along with the cellular and tissue protection from damage induced by the exposition to surgical light.
  • CBD is a safe and an effective natural molecule for staining biological tissues and structures that can be used in surgical procedures, such as chromovitrectomy, and it not only provides a clear differentiation between the target and surrounding structures by providing an adequate identification and manipulation of the biological membranes and structures for the ophthalmic surgeon but also minimizes iatrogenic retinal complications associated with the surgical or medical procedure.
  • This innovative approach therefore, offers a saferand more effective method for ocular surgeries, potentially revolutionizingthe field of ophthalmology and significantly improving surgical outcomes and patient safety.
  • HU-331 displays a potential anticancer therapeutic activity without some of the known adverse events associated with traditional anticancer agent, exhibiting to be much less cardiotoxic than chemotherapy drug doxorubicin (Kogan et al., 2007b, 2007a; Trac et al., 2021).
  • doxorubicin chemotherapy drug
  • TB is used as a visual aid during ophthalmic surgical vitrectomy procedures to stain the epiretinal membranes and facilitate their removal.
  • TB ophthalmic drops are utilised in posterior eye surgery to selectively stain membranes, such as Epiretinal Membranes and Internal Limiting Membranes, to improve surgical outcomes.
  • compositions are to be used as a practice for dyeing or staining biological membranes and structures in surgery, in order to facilitate their identification and biomolecular membrane composition during surgical procedures such as vitreoretinal surgery, resulting in the visualization of different types of ocular membranes and tissues along with the cellular and tissue protection from damage induced by the exposition to surgical light.
  • the present invention describes the use of a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach in surgery, such as vitreoretinal.
  • a pharmaceutical compositions for dyeing or staining membranes and other biological structures using a natural or synthetic CBD- based vital dye isolated and/or associated with other dyes, namely BBG and/or TB, as a promising approach in surgery, such as vitreoretinal.
  • Those pharmaceutical compositions are to be used as a practice for dyeing or staining biological membranes and structures in surgery, in order to facilitate their identification and biomolecular membrane composition during surgical procedures such as vitreoretinal surgery, resulting in the visualization of different types of ocular membranes and tissues along with the cellular and tissue protection from damage induced by the exposition to surgical light.
  • the present invention proposes a pharmaceutical formulation with the following composition:
  • composition of Cannabinoid-based vital dye contains the main active ingredient (Cannabinoids) mainly CBD- based stain responsible for staining biological tissues and structures during surgical procedures that can be either natural or synthetic, which can be either isolated and/or associated with other dyes, including but not limited to BBG and/or TB.
  • CBD- based stain responsible for staining biological tissues and structures during surgical procedures that can be either natural or synthetic, which can be either isolated and/or associated with other dyes, including but not limited to BBG and/or TB.
  • Cannabinoids could also have neuroprotective and plasticity-mediating properties, along with anti-inflammatory and antioxidant properties that could provide ocular protection during surgery.
  • composition of natural or synthetic CBD-based vital dye and/or associated with other dyes namely BBG and/or TB
  • This formulation contains the main active ingredient (Cannabinoids) mainly CBD- based stain responsible for staining biological tissues and structures during surgical procedures that can be either natural or synthetic, and/or associated with other dyes, namely BBG and/or TB.
  • CBD- based stain responsible for staining biological tissues and structures during surgical procedures that can be either natural or synthetic, and/or associated with other dyes, namely BBG and/or TB.
  • Composition of natural or synthetic CBD-based vital dye and/or associated with other dyes, namely BBG and/or TB, include acceptable pharmaceutical vehicles including but not limited to acetic acid, benzyl alcohol, borax, boric acid, BSS, calcium chloride, carbomer 934, carbopol, chondroitin sulphate, citric acid, dextran sodium polysorbate, glycocholic acid, hyaluronic acid, magnesium chloride, metaphosphoric acid, methylcellulose and its derivatives, phenylphosphate, phosphate buffer, polyethylene glycol, polyvinyl alcohol, potassium chloride, potassium phosphate, propylene glycol, purified water, sodium acetate, sodium chloride, sodium citrate, sodium edetate, sodium phosphate, sodium phthalate, and/or tweens, among others.
  • acceptable pharmaceutical vehicles including but not limited to acetic acid, benzyl alcohol, borax, boric acid, BSS, calcium chloride, carbomer 934, carbopol,
  • compositions selectively stain the biological structure 00 interest, leaving the surrounding structures undyed or less dyed, staining the target biological membranes and structures at a concentration that is physiologically and toxicologically acceptable, allowing ie>r the use 00 the minimum concentration 00 dye that provides visible differentiation between the selected biological membranes and the surrounding.
  • concentration physiologically and toxicologically acceptable
  • any remaining pharmaceutical composition in the surgical and medical Held is promptly removed aESer the procedure, Elirther reducing the possibility oESpost-process adverse effects.
  • oH natural dyes including: easy identification oESeye membrane and biological layers to identify and remove; prevention of side effects caused by incomplete removal of membranes and biological structures; reducing the time of surgery with reduction in medical and hospital fees; increased safety because the proposed dye is a natural dye, alone or in combination with other dyes and all the alternatives on the market today have demonstrated toxicity; and possible antioxidant and antiinflammation effect associated with the cannabinoid molecules along with the targeted delivery strategy for BBG and/or TB.
  • the overall process of pharmaceutical purposed composition preparation includes diluting the selected dyes with or without pharmaceutical vehicle to achieve the homogeneous final concentrations of:
  • Natural or synthetic CBD-based vital dye as the main dye ranging from 0.001 to 10%, preferably of 0.005 to 0.5%, even more definitely in the optimal concentration of 0.05%.
  • Trypan blue 0.001 to 5% of the total composition, preferably of 0.04 to 0.2%.
  • the method for staining biological material such as biological tissue, membranes or other structures of the eye includes the application of a pharmaceutical composition according to the present invention, topically or by injection. This application can be done during a surgical procedure or any other procedure that requires staining of a biological material and/ or structure.
  • the packaging material and raw materials are received, and the raw materials are weighed. Handling and/ or filtration takes place in an ISO 8 class room. In-process quality control is performed before septic or aseptic filling. Should the filling be aseptic, it follows the flow: Filling in the ISO 5 class room > Sealing in ISO 7 class room > Sterilization in the final sterilization room. Should the filling be septic, it follows the flow: Sterilizing Filtration in ISO 5 class room > Filling in ISO 5 class room > Sealing in ISO 7 class room. Packaging and quality control of the finished product then follows.
  • a natural or synthetic CBD-based vital dye and brilliant blue were weighted in separate and diluted together/or without a pharmaceutical vehicle to achieve amounts of a natural or synthetic CBD-based vital dye ranging from 0.001 to 10%, preferably of 0.005 to 0.5%, even more definitely in the optimal concentration of 0.05% and brilliant blue of 0.025 to 0.05% of the total composition, preferably 0.045 to 0.055% to obtain final homogeneous composition.
  • a natural or synthetic CBD-based vital dye and trypan blue were weighted in separate and diluted together/or without a pharmaceutical vehicle to achieve amounts of a natural or synthetic CBD-based vital dye ranging from 0.001 to 10%, preferably of 0.005 to 0.5%, even more definitely in the optimal concentration of 0.05% and trypan blue of 0.001 to 5% of the total composition, preferably of 0.04 to 0.2% to obtain final homogeneous composition.
  • a pharmaceutical composition having a natural or synthetic CBD-based vital dye ranging from 0.001 to 10%, preferably of 0.005 to 0.5%, even more definitely in the optimal concentration of 0.05%, brilliant blue of 0.025 to 0.05% of the total composition, preferably 0.045 to 0.055% and trypan blue of 0.001 to 5% of the total composition, preferably of 0.04 to 0.2% to obtain final homogeneous composition.
  • Example 5 Pharmaceutical compositions with different concentrations of a natural or synthetic CBD-based vital dye alone or in combination with Indocyanine Green
  • RODRIGUES E.B., MEYER, C.H., MENNEL, S vigorous FARAH, M.E., 2007.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Optics & Photonics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne l'utilisation d'une composition pharmaceutique pour teindre ou colorer des membranes et d'autres structures biologiques à l'aide d'un colorant vital à base de CBD naturel ou synthétique isolé et/ou associé à d'autres colorants, à savoir le BBG et/ou le TB, en tant qu'approche prometteuse pendant des procédures chirurgicales ou médicales, comme la chirurgie vitréo-rétinienne. L'utilisation de tels composés pour la préparation de compositions tinctoriales ou de coloration afin de faciliter leur identification et la composition de leur membrane biomoléculaire, permet de visualiser différents types de membranes et de tissus oculaires ainsi que la protection cellulaire et tissulaire contre les dommages induits par l'exposition à la lumière chirurgicale. La présente invention décrit l'ensemble du processus, depuis la production de la composition, sa formulation et les études menées, jusqu'à la méthode de coloration des membranes et des structures biologiques pour améliorer leur identification et leur manipulation adéquates, répondant ainsi au défi posé par la complexité de la procédure chirurgicale, principalement la chromo-vitrectomie.
PCT/IB2024/053301 2024-04-01 2024-04-04 Compositions pharmaceutiques pour colorer des membranes et d'autres structures biologiques à l'aide d'un colorant vital à base de cbd naturel ou synthétique isolé et/ou associé à d'autres colorants pour une chirurgie vitréo-rétinienne Pending WO2025210386A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PT11935524 2024-04-01
PT119355 2024-04-01

Publications (1)

Publication Number Publication Date
WO2025210386A1 true WO2025210386A1 (fr) 2025-10-09

Family

ID=90720166

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2024/053301 Pending WO2025210386A1 (fr) 2024-04-01 2024-04-04 Compositions pharmaceutiques pour colorer des membranes et d'autres structures biologiques à l'aide d'un colorant vital à base de cbd naturel ou synthétique isolé et/ou associé à d'autres colorants pour une chirurgie vitréo-rétinienne

Country Status (1)

Country Link
WO (1) WO2025210386A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016187722A1 (fr) * 2015-05-27 2016-12-01 Mary Lynch Utilisation de cannabinoïdes dans le traitement de l'inflammation et/ou de la douleur oculaire
WO2022204111A1 (fr) * 2021-03-23 2022-09-29 Murphy Brian Stuart Composition pour traiter des affections ophtalmiques et procédés d'utilisation de celle-ci

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016187722A1 (fr) * 2015-05-27 2016-12-01 Mary Lynch Utilisation de cannabinoïdes dans le traitement de l'inflammation et/ou de la douleur oculaire
WO2022204111A1 (fr) * 2021-03-23 2022-09-29 Murphy Brian Stuart Composition pour traiter des affections ophtalmiques et procédés d'utilisation de celle-ci

Non-Patent Citations (49)

* Cited by examiner, † Cited by third party
Title
AGUILERA TEBA, F., MOHR, A., ECKARDT, C., WONG, D., KUSAKA, S., JOONDEPH, B.C., FERON, E.J., STALMANS, P,VAN OVERDAM, K., MELLES, : "Trypan blue staining in vitreoretinal surgery", OPHTHALMOLOGY, vol. 110, 2003, pages 2409 - 2412, Retrieved from the Internet <URL:https://doi.org/10.1001/archopht.1978.03910050289022>
AIELLO, FGALLO AFFLITTO, GLI, J.-P.OMARTUCCI, ACESAREO, MNUCCI, C: "CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing", J CLIN MED, 2020, pages 9, Retrieved from the Internet <URL:https://doi.org/10.3390/jcm9124036>
ATALAY, S., JAROCKA-KARPOWICZ, I., SKRZYDLEWSKA, E.: "Antioxidative and Anti-Inflammatory Properties of Cannabidiol", ANTIOXIDANTS, vol. 9, 2019, pages 21, Retrieved from the Internet <URL:https://doi.org/10.3390/antiox9010021>
BACSAL, K.M.E., CHEE, S.-P.: "Trypan blue-associated retinal toxicity post complicated cataract surgery", EYE, vol. 20, 2006, pages 1310 - 1311, Retrieved from the Internet <URL:https://doi.org/10.1038/sj.eye.6702164>
BAKRI, S..: " Use of triamcinolone during vitrectomy surgery to visualize membranes and vitreous.", CLINICAL OPHTHALMOLOGY, 2008, pages 891, Retrieved from the Internet <URL:https://doi.org/10.2147/OPTH.S3434>
BOROWSKA-FIELDING, J., MURATAEVA, N., SMITH, B., SZCZESNIAK, A.-M., LEISHMAN, E., DAILY, L., TOGURI, J.T.,HILLARD, C.J., ROMERO, J: "Revisiting cannabinoid receptor 2 expression and function in murine retina", NEUROPHARMACOLOGY, vol. 141, 2018, pages 21 - 31, Retrieved from the Internet <URL:https://doi.org/10.1016/j.neuropharm.2018.08.007>
BOUSKILA, J., HARRAR, V., JAVADI, P., BEIERSCHMITT, A., PALMOUR, R., CASANOVA, C., BOUCHARD, J.-F., PTITO, M: "Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys", NEURAL PLAST, vol. 2016, 2016, pages 1 - 12, Retrieved from the Internet <URL:https://doi.org/10.1155/2016/1253245>
BOUSKILA, JBLEAU, MMICAELO-FERNANDES, CBOUCHARD, J.-FPTITO, M: "The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors", CELLS, vol. 10, 2021, pages 3160, Retrieved from the Internet <URL:https://doi.org/10.3390/cells10113160>
BRADSHAW, H.B., WALKER J.M.., BR J PHARMACOL, vol. 144, 2005, pages 459 - 465, Retrieved from the Internet <URL:https://doi.org/10.1038/sj.bjp.0706093>
BROD, R.D: "The Journal of Lancaster General", 2009, SPRING., article "Surgery for Diseases of the Vitreous and Retina"
BURK, S.EDA MATA, A.PSNYDER, M.EROSA, R.HFOSTER, R.E: "Indocyanine green-assisted peeling of the retinal internal limiting membrane13The authors have no financial interest in products mentioned in this article", OPHTHALMOLOGY, vol. 107, 2000, pages 2010 - 2014, Retrieved from the Internet <URL:https://doi.org/10.1016/S0161-6420(00)00375-4>
DELYFER, M., LEGOUT, P., LE GOFF, M., BLAIZEAU, M., ROUGIER, M., SCHWEITZER, C., KOROBELNIK, J., DELCOURT, C.: "Prevalence of epiretinal membranes in the ageing population using retinal colour images and SD-OCT: the Alienor Study", ACTA OPHTHALMOL, vol. 98, 2020, XP072397578, Retrieved from the Internet <URL:https://doi.org/10.1111/aos.14422> DOI: 10.1111/aos.14422
DHALIWAL, R.SDHALIWAL, K.V.SSINGH, MKAKKAR, A: "Stains and dyes in Ophthalmology", GLOBAL JOURNAL OF CATARACT SURGERY AND RESEARCH IN OPHTHALMOLOGY, vol. 1, 2022, pages 81, Retrieved from the Internet <URL:https://doi.org/10.25259/GJCSRO_5_2022>
ENAIDA, H., ISHIBASHI, T.: "Brilliant Blue in VitreoretinalSurgery, in: Vital Dyes in VitreoretinalSurgery.", KARGER, 2008, pages 115 - 125, Retrieved from the Internet <URL:https://doi.org/10.1159/000138989>
FARAH, M.E., MAIA, M., RODRIGUES, E.B.: " Dyes in Ocular Surgery: Principles for Use in Chromovitrectomy", AM J OPHTHALMOL, vol. 148, 2009, pages 332 - 340, Retrieved from the Internet <URL:https://doi.org/10.1016/j.ajo.2009.04.003>
FERNANDEZ-RUIZ, J., SAGREDO, O., PAZOS, M.R., GARCIA, C., PERTWEE, R., MECHOULAM, R., MARTINEZ-ORGADO, J.: "Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?", BR J CLIN PHARMACOL, vol. 75, 2013, pages 323 - 333, XP055509067, Retrieved from the Internet <URL:https://doi.org/10.1111/j.1365-2125.2012.04341.x> DOI: 10.1111/j.1365-2125.2012.04341.x
FORRESTER, J. VXU, H: "Good news-bad news: The Yin and Yang of immune privilege in the eye", FRONT, 2012, Retrieved from the Internet <URL:https://doi.org/10.3389/fimmu.2012.00338>
GANDORFER, A., HARITOGLOU, C., KAMPIK, A: "Vital Dyes in Vitreoretinal Surgery", KARGER, 2008, pages 69 - 81, Retrieved from the Internet <URL:https://doi.org/10.1159/000138974>
GUBER, J., PERENI, I., SCHOLL, H.P.N., GUBER, I., HAYNES, R.J.: " Outcomes after Epiretinal Membrane Surgery with or Without Internal Limiting Membrane Peeling", OPHTHALMOL THER, vol. 8, 2019, pages 297 - 303, Retrieved from the Internet <URL:https://doi.org/10.1007/s40123-019-0185-7>
IBEAS BIH, CCHEN, TNUNN, A.V.WBAZELOT, MDALLAS, MWHALLEY, B.J: "Molecular Targets of Cannabidiol in Neurological Disorders", NEUROTHERAPEUTICS, vol. 12, 2015, pages 699 - 730, XP036028978, Retrieved from the Internet <URL:https://doi.org/10.1007/s13311-015-0377-3> DOI: 10.1007/s13311-015-0377-3
IRIYAMA, A., UCHIDA, S., YANAGI, Y., TAMAKI, Y., INOUE, Y., MATSUURA, K., KADONOSONO, K., ARAIE, M., .: "Effects of Indocyanine Green on Retinal Ganglion Cells", INVESTIGATIVE OPTHALMOLOGY& VISUALSCIENCE, vol. 45, 2004, pages 943, Retrieved from the Internet <URL:https://doi.org/10.1167/iovs.03-1026>
ISENMANN, EVEIT, SSTARKE, LFLENKER, UDIEL, P: "Effects of Cannabidiol Supplementation on Skeletal Muscle Regeneration after Intensive Resistance Training", NUTRIENTS, vol. 13, 2021, pages 3028, Retrieved from the Internet <URL:https://doi.org/10.3390/nu13093028>
KOGAN, N.M., BLAZQUEZ, C., ALVAREZ, L., GALLILY, R., SCHLESINGER, M., GUZMAN, M., MECHOULAM, R.,.: "Cannabinoid Quinone Inhibits Angiogenesis by Targeting Vascular Endothelial Cells", MOL PHARMACOL, vol. 70, 2006, pages 51 - 59, Retrieved from the Internet <URL:https://doi.org/10.1124/mol.105.021089>
KOGAN, N.M., SCHLESINGER, M., PRIEL, E., RABINOWITZ, R., BERENSHTEIN, E., CHEVION, M., MECHOULAM, R.: "HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor", MOL CANCER THER, vol. 6, 2007, pages 173 - 183, Retrieved from the Internet <URL:https://doi.org/10.1158/1535-7163.MCT-06-0039>
KOGAN, N.MSCHLESINGER, MPETERS, MMARINCHEVA, GBEERI, RMECHOULAM, R: "A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less CardiotoxicThan Doxorubicin: A Comparative in Vivo Study", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 322, 2007, pages 646 - 653, Retrieved from the Internet <URL:https://doi.org/10.1124/jpet.107.120865>
LU, H.-CMACKIE, K: "An Introduction to the Endogenous Cannabinoid System", BIOL PSYCHIATRY, vol. 79, 2016, pages 516 - 525, XP029457668, Retrieved from the Internet <URL:https://doi.org/10.1016/j.biopsych.2015.07.028> DOI: 10.1016/j.biopsych.2015.07.028
MANTELLI, FMAURIS, JARGUESO, P: "The ocular surface epithelial barrier and other mechanisms of mucosal protection: from allergy to infectious diseases", CURR OPIN ALLERGY CLIN IMMUNOL, vol. 13, 2013, pages 563 - 8, Retrieved from the Internet <URL:https://doi.org/10.1097/ACI.Ob013e3283645899>
MARC VECKENEER ET AL: "Novel 'heavy' dyes for retinal membrane staining during macular surgery: multicenter clinical assessment", ACTA OPHTHALMOLOGICA: THE OPHTHALMOLOGICAL JOURNAL OF THE NORDIC COUNTRIES, vol. 92, no. 4, 1 June 2014 (2014-06-01), Denmark, pages 339 - 344, XP055311389, ISSN: 1755-375X, DOI: 10.1111/aos.12208 *
MCCORMICK, C.R., REDDEN, R.S., HURST, A.J., KLEIN, R.M.: "On the selection of endogenous and exogenous signals", R SOC OPEN SCI, vol. 6, 2019, pages 190134, Retrieved from the Internet <URL:https://doi.org/10.1098/rsos.190134>
MCPARTLAND J ED - BOUCHARA JEAN-PHILIPPE ET AL: "PATHOGENICITY OF PHOMOPSIS GANJAE ON CANNABIS SATIVA AND THE FUNGISTATIC EFFECT OF CANNABINOIDS PRODUCED BY THE HOST", MYCOPATHOLOGIA, KLUWER ACADEMIC PUBLISHERS, XX, vol. 87, no. 3, 1 January 1984 (1984-01-01), pages 149 - 153, XP009000509, ISSN: 0301-486X, DOI: 10.1007/BF00436900 *
MECHA, MTORRAO, A.SMESTRE, LCARRILLO-SALINAS, F.JMECHOULAM, RGUAZA, C: "Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress", CELL DEATH DIS, vol. 3, 2012, pages e331 - e331, Retrieved from the Internet <URL:https://doi.org/10.1038/cddis.2012.71>
NARAYANAN, RMUNGCAL, J.KKENNEY, M.CSEIGEL, G.MKUPPERMANN, B.D: "Toxicity of Triamcinolone Acetonide on Retinal Neurosensory and Pigment Epithelial Cells", INVESTIGATIVE OPTHALMOLOGY & VISUAL SCIENCE, vol. 47, 2006, pages 722, Retrieved from the Internet <URL:https://doi.org/10.1167/iovs.05-0772>
OLIVEIRA, TMAIA, M: "Advances in Vitreoretinal Surgery", J CLIN MED, vol. 11, 2022, pages 6428, Retrieved from the Internet <URL:https://doi.org/10.3390/jcm11216428>
PETERSEN, K.K.-SRICE, A.S.CARENDT-NIELSEN, L: "The use of cannabidiol (CBD) as an analgesic component", THE LANCET REGIONAL HEALTH - EUROPE, 2023, pages 100791, Retrieved from the Internet <URL:https://doi.org/10.1016/j.lanepe.2023.100791>
RODRIGUES, E.B., COSTA, E.F., PENHA, F.M., MELO, G.B., BOTTOS, J., DIB, E., FURLANI, B., LIMA, V.C., MAIA, M.,MEYER, C.H., HOFLING: "The Use of Vital Dyes in Ocular Surgery", SURV OPHTHALMOL, vol. 54, 2009, pages 576 - 617, XP026458320, Retrieved from the Internet <URL:https://doi.org/10.1016/j.survophthal.2009.04.011>
RODRIGUES, E.B., MEYER, C.H., MENNEL, S., FARAH, M.E.: "MECHANISMS OF INTRAVITREAL TOXICITY OF INDOCYANINE GREEN DYE ", RETINA, vol. 27, 2007, pages 958 - 970, Retrieved from the Internet <URL:https://doi.org/10.1097/01.iae.0000253051.01194.ab>
SAMUEL, M.ADESAI, U.RSTRASSMAN, IABUSAMAK, M: "Intraocular Irrigating Solutions. A Clinical Study of BSS Plus° and Dextrose Bicarbonate Fortified BSS° as an Infusate during Pars Plana Vitrectomy", INDIAN JOURNAL OF OPHTHALMOLOGY, 2003, pages 237 - 242
SARAIVA SOFIA M. ET AL: "Cannabinoid-Based Ocular Therapies and Formulations", PHARMACEUTICS, vol. 15, no. 4, 27 March 2023 (2023-03-27), Switzerland, pages 1077, XP093233563, ISSN: 1999-4923, DOI: 10.3390/pharmaceutics15041077 *
SARAIVA, S.M., MARTIN-BANDERAS, L., DURAN-LOBATO, M.: " Cannabinoid-Based Ocular Therapies and Formulations", PHARMACEUTICS, vol. 15, 2023, pages 1077, Retrieved from the Internet <URL:https://doi.org/10.3390/pharmaceutics15041077>
SCHWITZER, TSCHWAN, RANGIOI-DUPREZ, KGIERSCH, ALAPREVOTE, V: "The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications", NEURAL PLAST 2016, 2016, pages 1 - 10, Retrieved from the Internet <URL:https://doi.org/10.1155/2016/2916732>
SONI, A., PARAMESWARAPPA, D.C., TYAGI, M., SAHOO, N.K., DOGRA, A., PAPPURU, R.R., CHHABLANI, J.: "Brilliant Blue G toxicity in macular hole surgeries: A report on combined phototoxicity and dye-induced macular damage", SEMIN OPHTHALMOL, vol. 37, 2022, pages 117 - 122, Retrieved from the Internet <URL:https://doi.org/10.1080/08820538.2021.1928717>
TAHIR, M.N., SHAHBAZI, F., RONDEAU-GAGNE, S., TRANT, J.F., CANNABIS RES, vol. 3, 2021, pages 7, Retrieved from the Internet <URL:https://doi.org/10.1186/s42238-021-00062-4>
THOMPSON, J.T: "Proliferative Vitreoretinopathy, in: Retina", 2006, ELSEVIER, pages: 2283 - 2309
THOMSON, BRODIE.J., HANNA, S., SCHWARZENBERG, A., KIANI, P., BIZZOTTO, D., KENNEPOHL, P., DAVIES, A.,ROGGEN, M., SAMMIS, G.M: "CBD hydroxyquinone photo-isomerises to a highly reactive intermediate", SCI REP, vol. 13, 2023, pages 6967, Retrieved from the Internet <URL:https://doi.org/10.1038/s41598-023-33815-7>
TRAC, JKECK, J.MDEWEESE, J.E: "Cannabidiol oxidation product HU-331 is a potential anticancer cannabinoid-quinone: a narrative review", JCANNABIS RES, vol. 3, no. 11, 2021, Retrieved from the Internet <URL:https://doi.org/10.1186/s42238-021-00067-z>
WALDO ZUARDI, A., ALEXANDRE S. CRIPPA, J., E.C. HALLAK, J., BHATTACHARYYA, S., ATAKAN, Z., MARTIN-SANTOS, R.,K. MCGUIRE, P., SILVE: "A Critical Review of the Antipsychotic Effects of Cannabidiol: 30 Years of a Translational Investigation", CURR PHARM DES, vol. 18, 2012, pages 5131 - 5140, Retrieved from the Internet <URL:https://doi.org/10.2174/138161212802884681>
WATKINS, A.R: "Cannabinoid interactions with ion channels and receptors", CHANNELS, vol. 13, 2019, pages 162 - 167, Retrieved from the Internet <URL:https://doi.org/10.1080/19336950.2019.1615824>
ZANTUT, P.R.A., VERAS, M.M., YARIWAKE, V.Y., TAKAHASHI, W.Y., SALDIVA, P.H., YOUNG, L.H., DAMICO, F.M.,FAJERSZTAJN, L.: "Effects of cannabis and its components on the retina: a systematic review.", CUTAN OCUL TOXICOL, vol. 39, 2020, pages 1 - 9, Retrieved from the Internet <URL:https://doi.org/10.1080/15569527.2019.1685534>
ZHORNITSKY, S., POTVIN, S.: " Cannabidiol in Humans-The Quest for Therapeutic Targets.", PHARMACEUTICALS, vol. 5, 2021, pages 529 - 552, Retrieved from the Internet <URL:https://doi.org/10.3390/ph5050529>

Similar Documents

Publication Publication Date Title
Ahmed et al. Ocular drug delivery: a comprehensive review
US9844530B1 (en) Ophthalmic solutions for glaucoma and conjunctivitis treatment
US20040192647A1 (en) Method for topical treatment of eye disease and composition and device for said treatment
HK1202427A1 (zh) 眼科载体体系
JP2012525398A (ja) 眼科障害を治療するためのトコトリエノールの局所、眼周囲または眼内使用
CN113518619A (zh) 用于治疗眼部新生血管形成的药物组合物
AU2014332488A1 (en) Methods and compositions for treating and preventing signs or symptoms of eye disease
Badaro et al. Soluble lutein in combination with brilliant blue as a new dye for chromovitrectomy
Penha et al. Effects of subretinal injections of indocyanine green, trypan blue, and glucose in rabbit eyes
EP2696900B1 (fr) Colorants pour membranes et structures biologiques
Sousa-Martins et al. Use of lutein and zeaxanthin alone or combined with Brilliant Blue to identify intraocular structures intraoperatively
JP2016512562A (ja) マイクロエマルジョン局所送達プラットフォーム
JP2021505650A (ja) 眼用薬物製剤及びその使用
JP6934421B2 (ja) 視神経症を処置するためのマスティックガムの単離画分の使用
KR20150032552A (ko) 치료 제제 및 치료 방법
WO2025210386A1 (fr) Compositions pharmaceutiques pour colorer des membranes et d&#39;autres structures biologiques à l&#39;aide d&#39;un colorant vital à base de cbd naturel ou synthétique isolé et/ou associé à d&#39;autres colorants pour une chirurgie vitréo-rétinienne
JP2006298876A (ja) サーチュインの活性化剤を含む各種眼疾患治療用組成物
EP3682867B1 (fr) Composition ophtalmique contenant de la lutéine
CA3028294A1 (fr) Compositions pharmaceutiques pour colorer des membranes et d`autres structures biologiques
Singh et al. In vitro and in vivo evaluation of stimuli sensitive hydrogel for ophthalmic drug delivery
Romano et al. Efficacy and Safety Profile of Vital Dyes
JP2011153156A (ja) サーチュインの活性化剤を含む各種眼疾患治療用組成物
WO2021243432A1 (fr) Compositions pharmaceutiques pour colorer des membranes et d&#39;autres structures biologiques
US20240299291A1 (en) Ophthalmic preparation administered by eye drops and used for preventing and treating dry macular degeneration and retinal light damage
HK40062272A (en) Pharmaceutical composition for the treatment of ocular neovascularisation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24717806

Country of ref document: EP

Kind code of ref document: A1