Method of treating eye diseases with krill oil
Inventors
Myhren, Finn • Hals, Petter-Arnt • Hoem, Nils • Storsve, Andreas Berg • SUBBAIAH, PAPASANI V. • Yalagala, Poorna • Dhavamani, Sugasini • Tai, Leon
Assignees
Aker Biomarine Human Ingredients AS • US Department of Veterans Affairs • University of Illinois System
Publication Number
US-11744864-B2
Publication Date
2023-09-05
Expiration Date
2041-03-31
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Abstract
The present invention provides compositions comprising phosphatidylcholine derived compounds carrying an omega-3 fatty acid for use in prophylaxis or therapy, particularly when administered systemically. This invention further relates to a modified krill oil composition enriched in LPC-DHA and LPC-EPA, methods of making and methods of using to treat neurological and ocular disorders.
Core Innovation
The invention provides compositions comprising phosphatidylcholine derived compounds carrying an omega-3 fatty acid, particularly lysophosphatidylcholine (LPC) compounds such as LPC-DHA and LPC-EPA, for use in prophylaxis or therapy of neurological and ocular disorders. A modified krill oil composition enriched in LPC-DHA and LPC-EPA is disclosed, along with methods of making and using this composition to treat eye diseases, including dry eye disease and neurodegenerative ocular diseases.
The problem addressed is the inefficiency of current omega-3 supplements in enriching brain and retinal DHA and EPA due to their absorption mainly as triacylglycerol (TAG), which does not generate the lysophosphatidylcholine forms required for transport across blood barriers such as the blood brain barrier and blood retinal barrier. Conventional DHA supplements, including fish oil, algal oil, and krill oil, have shown disappointing clinical results in treating neurological and ocular diseases due to this inefficiency.
The inventors discovered that pre-treating dietary krill oil with a lipase specific for the sn-1 position generates LPC-DHA and LPC-EPA, which significantly enrich brain and retinal levels of these fatty acids and increase brain derived neurotrophic factor (BDNF). Feeding lipase-treated krill oil (LTKO) to mice was 5- to 70-fold more effective in enriching brain DHA and EPA than untreated krill oil (UTKO), unlike fish oil which showed no effect whether treated or not. This provides a novel strategy to target dietary DHA and EPA to the brain and eye to prevent and treat neurological and ocular diseases.
Claims Coverage
The patent contains one independent claim focused on a method for improving symptoms of eye diseases by administering formulations containing lysophosphatidylcholine (LPC) compounds.
Method of treating eye diseases with LPC compositions
Administering an effective amount of a pharmaceutical or nutraceutical formulation comprising a lysophosphatidylcholine (LPC) composition that includes LPC-compounds of formulas 1 to 8, or combinations thereof, for improving, controlling, reducing, or alleviating symptoms of an eye disease or condition.
Specific LPC-composition characteristics
The LPC composition may have R1 and R2 as OH groups; may comprise LPC-DHA and LPC-EPA in specified molar ratios ranging from 1:1 to 3:1 or 1:1 to 5:1; and may include additional lipids such as triglycerides, free fatty acids, ethyl esters, phosphatidylethanolamine, and phosphatidylcholine.
Treatment of specific eye diseases
The method targets dry eye disease and neurodegenerative diseases of the eye, such as age-related macular degeneration, diabetic retinopathy, non-proliferative and proliferative retinopathies, diabetic macular edema, retinitis pigmentosa, central vein occlusion, and glaucoma.
Modes of administration
The LPC compositions can be administered orally or via intravascular (including intravenous) routes.
Formulation components and subject applicability
Formulations can include 10% to 100% by weight total LPC, with optional components like lutein, astaxanthin, zeaxanthin. The subject of treatment can be a mammalian, particularly a human subject.
The independent claim covers methods of treating eye diseases through pharmaceutical or nutraceutical formulations containing specific LPC compounds with controlled compositions and ratios, administered via oral or intravascular routes, targeting multiple ocular conditions and designed for mammalian use.
Stated Advantages
Lipase-treated krill oil compositions significantly increase brain and retinal DHA and EPA levels compared to untreated krill oil or fish oil.
The LPC form of DHA and EPA enhances transport across blood brain and blood retinal barriers via the Mfsd2a transporter.
Higher retinal EPA/DHA ratios achieved with the compositions modulate inflammatory status beneficially.
The approach provides a potential novel therapeutic strategy for neurodegenerative and ocular diseases including Alzheimer's, dry eye disease, and retinopathies.
Kits or formulations allowing oral or intravenous administration improve bioavailability and tissue enrichment.
Documented Applications
Treatment or prevention of eye diseases and conditions including dry eye disease, ocular surface disorders, and corneal lesions.
Treatment of neurodegenerative eye diseases such as age-related macular degeneration, diabetic retinopathy, non-proliferative retinopathy, proliferative retinopathy, diabetic macular edema, retinitis pigmentosa, central vein occlusion, and glaucoma.
Use in treating neurological diseases or disorders including Parkinson's, schizophrenia, traumatic brain injury, stroke, and Alzheimer's disease.
Treatment or prevention of liver diseases mitigated by DHA enrichment of the liver, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
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