Carrier composition for eye drops and pharmaceutical composition including the same
Inventors
Jun, Young Joo • Kim, Ji Hyun • YOO, Byung Woo • Choi, Ji Young
Assignees
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Publication Number
US-11260104-B2
Publication Date
2022-03-01
Expiration Date
Abstract
The present disclosure provides a carrier composition for eye drops in which a substance to be delivered is loaded in a carrier, wherein the substance to be delivered includes one or more selected from the group consisting of an anti-inflammatory agent, a glaucoma treatment agent, a calcium channel blocker (CCB), an NMDA-receptor blocker, an antioxidant, a nitric oxide synthase inhibitor, a heat shock protein (HSP), a cystinosis treatment agent, and an antibiotic, the carrier has a spherical shape, the carrier includes a multilayer shell in a region ranging from the center to the surface of the carrier, the multilayer shell includes a core located in the center of the carrier and including a carboxymethyl cellulose (CMC)-based hydrogel having a degree of substitution (D.S.) of 0.9, a first shell located on the surface of the core and including a CMC-based hydrogel having a degree of substitution of 0.8, a second shell located on the surface of the first shell and including a CMC-based hydrogel having a degree of substitution of 0.6, and a third shell including a CMC-based hydrogel having a degree of substitution of 0.65, and the multilayer shell includes the core having a radius equal to 25% of the radial length of the carrier, the first shell having a thickness equal to 20% of the radial length, the second shell having a thickness equal to 40% of the radial length, and the third shell having a thickness equal to 15% of the radial length, and a pharmaceutical composition including the same.
Core Innovation
The disclosed invention relates to a carrier composition for eye drops in which a substance to be delivered is loaded in a spherical carrier. The substance to be delivered comprises one or more selected from an anti-inflammatory agent, a glaucoma treatment agent, a calcium channel blocker (CCB), an NMDA-receptor blocker, an antioxidant, a nitric oxide synthase inhibitor, a heat shock protein (HSP), a cystinosis treatment agent, and an antibiotic. The carrier is designed to provide loading of these selected therapeutic substance categories for ophthalmic delivery.
The carrier has a multilayer shell in a region ranging from the center to the surface of the carrier. The multilayer shell comprises a core located in the center of the carrier and comprising a carboxymethyl cellulose (CMC)-based hydrogel having a degree of substitution (D.S.) of 0.9. A first shell is located on the surface of the core and comprises a CMC-based hydrogel having a degree of substitution of 0.8, and a second shell located on the surface of the first shell comprises a CMC-based hydrogel having a degree of substitution of 0.6.
A third shell is located on the surface of the second shell and comprises a CMC-based hydrogel having a degree of substitution of 0.65. The multilayer shell further specifies geometric ratios of the carrier, including the core having a radius equal to 25% of a radial length of the carrier, the first shell having a thickness equal to 20% of the radial length, the second shell having a thickness equal to 40% of the radial length, and the third shell having a thickness equal to 15% of the radial length. The overall structure provides an ocular eye-drop carrier based on CMC-based multilayer hydrogel layers with defined D.S. values and defined radial geometry.
Claims Coverage
The independent claim set out the core structural and compositional requirements for a spherical eye-drop carrier that includes a multilayer shell of CMC-based hydrogel layers with specific degrees of substitution and defined radial geometry, together with loading of selected therapeutic categories. Across dependent claims, the inventive subject matter is further refined with specific anti-inflammatory agents, quantitative particle-size constraints (D50), ophthalmic post-surgical anti-inflammatory/infection inhibition for an ophthalmic disease including cataract, and a filter-sterilization content-change constraint.
Spherical CMC-based multilayer hydrogel carrier for eye drops loaded with selected therapeutic categories
A carrier composition for eye drops in which a substance to be delivered is loaded in a carrier, where the substance to be delivered comprises one or more selected from an anti-inflammatory agent, a glaucoma treatment agent, a calcium channel blocker (CCB), an NMDA-receptor blocker, an antioxidant, a nitric oxide synthase inhibitor, a heat shock protein (HSP), a cystinosis treatment agent, and an antibiotic, and where the carrier has a spherical shape and comprises a multilayer shell in a region ranging from the center to the surface of the carrier.
Defined CMC hydrogel degrees of substitution across a multilayer shell
The carrier has a multilayer shell that comprises a core located in the center comprising a CMC-based hydrogel having a degree of substitution (D.S.) of 0.9, a first shell on the surface of the core comprising a CMC-based hydrogel having a degree of substitution of 0.8, a second shell on the surface of the first shell comprising a CMC-based hydrogel having a degree of substitution of 0.6, and a third shell on the surface of the second shell comprising a CMC-based hydrogel having a degree of substitution of 0.65.
Quantified radial geometry for multilayer hydrogel thickness and core radius
The multilayer shell comprises the core having a radius equal to 25% of a radial length of the carrier, the first shell having a thickness equal to 20% of the radial length, the second shell having a thickness equal to 40% of the radial length, and the third shell having a thickness equal to 15% of the radial length.
Selected anti-inflammatory agents for the delivered substance
The carrier composition includes an anti-inflammatory agent selected from dexamethasone, diclofenac, ketorolac, rimexolone, or difluprednate.
Particle size constraint expressed as D50 range
The carrier composition has an average particle diameter (D50) ranging from 1 to 500 nm.
Post-surgical inflammation or infection inhibition for an ophthalmic disease
The ophthalmic carrier composition inhibits inflammation or infection after surgery for an ophthalmic disease.
Cataract indication
The ophthalmic carrier composition is specified for use against cataract.
Filter sterilization preparation with limited absolute content change
A pharmaceutical composition is prepared by sterilizing a carrier composition using a filter, where the absolute value of the content change before versus after sterilization is less than 1%.
Overall, the claim set centers on a spherical eye-drop carrier having a CMC-based multilayer hydrogel shell with specified degrees of substitution (0.9 core; 0.8/0.6/0.65 shells) and specified radial geometry (25% core radius; 20%/40%/15% shell thicknesses), loaded with one or more therapeutic categories. Dependent features further specify anti-inflammatory agent candidates, constrain particle size (D50), narrow functional ophthalmic targeting to post-surgical inflammation/infection inhibition and specifically cataract, and impose a filter sterilization content-change limitation.
Stated Advantages
Long residence in the anterior segment.
Sustained release.
Improved comfort.
Reduced dosing frequency.
Filter-sterilization stability for hydrophobic drugs/excipients, with no substantial content/component change after 200 nm filtration.
Documented Applications
Eye-drop delivery for ophthalmic therapeutic substances, including use for cataract and for inhibiting inflammation or infection after surgery for an ophthalmic disease.
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