Combination therapeutics and methods for the treatment of neurodegenerative and other diseases
Inventors
Assignees
Publication Number
US-10828276-B2
Publication Date
2020-11-10
Expiration Date
2033-11-26
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Abstract
Embodiments of the present invention are directed to the administration of bryostatins and bryostatins and retinoids for the treatment of disease responsive to increases in alpha secretase activity. Inventions of the present application are directed to the treatment of neuro-degenerative diseases such as Hutchinson Disease, Parkinson's disease, Down's syndrome and Alzheimer's disease and virus latency diseases such as HIV and Herpes, cancers such as prostate, melanomas, lymphomas and renal cancers, esophageal and opthalmic diseases such as glaucoma.
Core Innovation
The invention is directed to pharmaceutical formulations and methods for treating diseases that respond to increases in alpha secretase activity, particularly neurodegenerative diseases like Alzheimer's, Parkinson's, Hutchinson's Disease, Down's syndrome, Kuru, Creutzfeldt-Jakob disease, as well as virus latency diseases such as HIV and Herpes, certain cancers, and ophthalmic diseases such as glaucoma. The approach involves the administration of bryostatins, or their analogs known as Bryoids, alone or in combination with retinoids, encapsulated together in nanospheres or dissolved in pharmaceutically acceptable oils for oral administration.
The key problem addressed is the lack of effective and convenient therapies for these diseases, many of which currently have very limited treatment options. The invention specifically responds to the need for therapeutics and combination therapeutics that act synergistically, are formulated for enhanced oral delivery, and do not require administration by specially trained healthcare providers.
The core pharmaceutical formulation comprises co-encapsulation of bryostatin-1 (or a specified Bryoid) and a retinoid (selected from retinoic acid, retinol, retinol acetate, retinol palmitate, 13-cis-retinoic acid, and bexarotene) within nanospheres made from an acid-resistant biopolymer, such as poly(D,L-lactide-co-glycoside). These nanospheres, with diameters ranging from 1 to 1000 nanometers, are designed to synergistically increase alpha secretase expression upon administration. The dosage forms can be lyophilized for aqueous reconstitution, or formulated as oral dosage forms such as tablets, capsules, gel caps, and powders. Additionally, co-dissolved oil-based formulations are described.
Claims Coverage
The claims present two independent inventive features relating to pharmaceutical formulations for treatment of diseases responsive to increased alpha secretase activity.
Pharmaceutical formulation comprising co-encapsulated bryostatin-1 and retinoid in polymer nanospheres
A pharmaceutical formulation includes: - An effective amount of bryostatin-1; - An effective amount of retinoid selected from retinoic acid, retinol, retinol acetate, retinol palmitate, 13-cis-retinoic acid, and bexarotene; - A plurality of nanospheres co-encapsulating the bryostatin-1 and retinoid in amounts effective to synergistically increase alpha secretase expression; - Each nanosphere has a diameter between 1 and 1000 nanometers; - Each nanosphere is formed of a polymer consisting of a poly(D, L-lactide-co-glycoside).
Formulation for treatment of diseases responsive to alpha secretase increases, with bryostatin-1 and retinoid co-encapsulated in biopolymer nanospheres
A formulation includes: - An effective amount of bryostatin-1 and an effective amount of retinoid; - The bryostatin and retinoid are co-encapsulated in a plurality of biopolymer nanospheres with diameters of one to 1000 nanometers; - The biopolymer is poly(D,L-lactide-co-glycoside); - The bryostatin-1 and retinoid are present at an effective amount to synergistically increase alpha secretase expression.
The claims broadly cover co-encapsulation of bryostatin-1 and specified retinoids in acid-resistant polymer nanospheres for synergistic upregulation of alpha secretase, and extend to oral and lyophilized formulations for treating neurodegenerative and other diseases.
Stated Advantages
Provides effective therapeutics and combination therapeutics that act synergistically for diseases responsive to alpha secretase activity.
Enables simple oral administration formulations, eliminating the need for specially trained healthcare providers.
Formulations can be lyophilized for reconstitution or prepared in oral dosage forms such as tablets, capsules, gel caps, and powders.
Utilizes acid-resistant polymer nanospheres for drug delivery, enabling passage through gastric acid and delivery to the small intestine for absorption.
Combination of bryostatin and retinoid in nanospheres or oil-based formulations allows for synergistic increase in alpha secretase expression.
Documented Applications
Treatment of neurodegenerative diseases including Alzheimer's Disease, Hutchinson's Disease, Parkinson's Disease, Kuru, Creutzfeldt-Jakob Disease, Down's syndrome, and spongiform encephalopathies.
Treatment of viral latency diseases such as HIV and Herpes.
Treatment of cancers including prostate cancer, melanomas, lymphomas, and renal cancers.
Treatment of ophthalmic diseases such as glaucoma.
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