IP Library › Granted Patent US 12,396,994
Granted Patent B2
US 12,396,994 · App. 16/875,440 · Granted Aug 26, 2025

Compositions for improving physiological function with age

Inventors: Thomas Larocca (Boulder, CO); Douglas Seals (Boulder, CO)
Assignee: The Regents Of The University Of Colorado, a body corporate
A61K31/522A23L33/15A61K31/19A61K31/353A61K31/593A61K31/7016
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Quick Facts
Patent No.
US 12,396,994
App. No.
16/875,440
Granted
Aug 26, 2025
Kind
B2
Abstract

Provided are methods for treating a disease or condition associated with reduced autophagy in a patient, which includes administering to the patient, either simultaneously or sequentially, a therapeutically effective amount of a synergistic combination of compounds from at least two and preferably three of the classes of compounds selected from a saccharide, a vitamin, a ketone body, a polyphenol, and a methylxanthine. The compounds may be present in a subtherapeutic effective amount relative to the compound's dosing when given as a single agent. Also provided are pharmaceutically acceptable compositions and kits including at least two and preferably three of the named classes of compounds.

Claims (22)

1. A method for treating a disease or condition associated with reduced autophagy in a human patient, comprising increasing autophagy in cells of said patient by administering to said patient a therapeutically effective amount of a combination consisting of between about 5 mM and about 10 mM trehalose or a pharmaceutically acceptable salt thereof, between about 1 nM and about 10 nM cholecalciferol or a pharmaceutically acceptable salt thereof, between about 0.5 M and about 5 UM epigallocatechin gallate or a pharmaceutically acceptable salt thereof, and optionally between about 0.5 μM and about 5 μM of a methylxanthine compound or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutical carrier,

wherein the trehalose or pharmaceutically acceptable salt thereof is administered in a total amount of about 1 to about 200 mg/kg of body weight of the patient per day, the cholecalciferol or pharmaceutically acceptable salt thereof is administered in a total amount of about 1 ng/kg to about 500 ng/kg of body weight of the patient per day, the epigallocatechin gallate or pharmaceutically acceptable salt thereof is administered in a total amount of about 0.5 μg/kg to about 300 μg/kg of body weight of the patient per day, and optionally the methylxanthine compound or pharmaceutically acceptable salt thereof is administered in a total amount of about 0.01 to about 10 mg/kg of body weight of the patient per day,

wherein the combination has a synergistic autophagy enhancement effect and increases autophagy in the cells of said patient by at least 10% as compared to the level of autophagy present in an untreated cell or a cell treated with a placebo.

2. The method of claim 1 , wherein the methylxanthine compound is selected from the group consisting of caffeine, aminophylline, 3-isobutyl-1-methylxanthine (IBMX), paraxanthine, pentoxifylline, theobromine, and theophylline.

3. The method of claim 1 , wherein the trehalose or pharmaceutically acceptable salt thereof is administered in a total amount of about 20 to about 80 mg/kg of body weight of the patient per day,

the cholecalciferol or pharmaceutically acceptable salt thereof is administered in a total amount of about 20 to about 100 ng/kg of body weight of the patient per day, and

the epigallocatechin gallate or pharmaceutically acceptable salt thereof is administered in a total amount of about 2 to about 100 μg/kg of body weight of the patient per day.

4. The method of claim 1 , wherein the disease or condition associated with reduced autophagy is aging, cardiovascular disease, neurodegenerative disease, or inflammatory disease.

5. The method of claim 1 , wherein the disease or condition associated with reduced autophagy is aging.

6. The method of claim 1 , comprising increasing a ratio of LC3-II protein to LC3-I protein in the cells of said patient.

7. The method of claim 1 , wherein autophagy in the cells of said patient is increased by at least 50% as compared to the level of autophagy present in an untreated cell or a cell treated with a placebo.

8. The method of claim 1 , wherein the disease or condition associated with reduced autophagy is cardiovascular disease.

9. A method for treating a chronic human disease in a human patient, comprising increasing autophagy in cells of said patient by administering to said patient a therapeutically effective amount of a combination consisting of trehalose or a pharmaceutically acceptable salt thereof, cholecalciferol or a pharmaceutically acceptable salt thereof, epigallocatechin gallate or a pharmaceutically acceptable salt thereof, and a methylxanthine compound or a pharmaceutically acceptable salt thereof,

wherein the trehalose or pharmaceutically acceptable salt thereof is administered in a total amount of about 1 to about 200 mg/kg of body weight of the patient per day, the cholecalciferol or pharmaceutically acceptable salt thereof is administered in a total amount of about 1 ng/kg to about 500 ng/kg of body weight of the patient per day, the epigallocatechin gallate or pharmaceutically acceptable salt thereof is administered in a total amount of about 0.5 μg/kg to about 300 μg/kg of body weight of the patient per day, and the methylxanthine compound or pharmaceutically acceptable salt thereof is administered in a total amount of about 0.01 to about 10 mg/kg of body weight of the patient per day,

wherein the combination increases autophagy in the cells of said patient by at least 10% as compared to the level of autophagy present in an untreated cell or a cell treated with a placebo and has a synergistic treatment effect for said chronic human disease, and

wherein the methylxanthine compound is selected from the group consisting of caffeine, aminophylline, 3-isobutyl-1-methylxanthine (IBMX), paraxanthine, pentoxifylline, theobromine, and theophylline.

10. The method of claim 9 , wherein the chronic human disease is selected from the group consisting of a cardiovascular disease, cancer, Type 2 diabetes, Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, psoriasis, and multiple sclerosis.

11. The method of claim 9 , wherein autophagy in the cells of said patient is increased by at least 50% as compared to the level of autophagy present in an untreated cell or a cell treated with a placebo.

12. The method of claim 9 , wherein the trehalose or pharmaceutically acceptable salt thereof is administered in a total amount of about 20 to about 80 mg/kg of body weight of the patient per day,

the cholecalciferol or pharmaceutically acceptable salt thereof is administered in a total amount of about 20 to about 100 ng/kg of body weight of the patient per day,

the epigallocatechin gallate or pharmaceutically acceptable salt thereof is administered in a total amount of about 2 to about 100 μg/kg of body weight of the patient per day, and the methylxanthine compound or pharmaceutically acceptable salt thereof is administered in a total amount of about 0.01 to about 0.5 mg/kg of body weight of the patient per day.

13. The method of claim 9 , wherein the chronic human disease is cardiovascular disease.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2020
From: LAROCCA, THOMAS; SEALS, DOUGLAS
To: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
Reel/Frame 052677/0189 →
Continuity (3)
Continuation In Part PCTUS2018061069 · Nov 14, 2018
Provisional Application 62586467 · Nov 15, 2017
Related Publication 20200276203A1 · Sep 3, 2020
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