CN-122028912-A - Use of alisretinate for reducing or inhibiting advanced glycation end products

Abstract

The present invention provides novel methods for reducing or inhibiting advanced glycation end products (AGEs) in a subject comprising administering to the subject a composition comprising an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analog, or derivative thereof. The invention also provides a composition comprising an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, for use in reducing or inhibiting advanced glycation end products (AGEs) in a subject.

Inventors

• YI RONGHUA
• Sean wells
• LIAO QILIN

Assignees

• 南京纽邦生物科技有限公司

Dates

Publication Date

20260512

Application Date

20241014

Priority Date

20231016

Claims (20)

1. 1. A method of reducing or inhibiting advanced glycation end products (AGEs) in a subject, comprising administering to the subject a composition comprising an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analog, or derivative thereof.
2. 2. The method of claim 1, wherein the method is used for anti-glycation.
3. 3. The method according to claim 1 or 2, wherein the method is used for reducing or preventing aging.
4. 4. The method of claim 3, wherein the aging is characterized by striae, loss of elasticity, a orange-peel or dull appearance of the skin, reduced epidermis and dermis thickness, epidermal atrophy, reduced basal keratinocyte mitosis, reduced proliferation capacity, cellular aging, atrophy of the extracellular matrix of the dermis, altered physiological properties of connective tissue.
5. 5. The method of any one of claims 1 to 4, wherein the reduction or inhibition of advanced glycation end products (AGEs) is achieved by scavenging chronic ROS, reducing H 2 O 2 and/or MMP-1 expression.
6. 6. The method of claim 5, wherein said scavenging of chronic ROS comprises increasing the activity of antioxidant enzymes such as SOD, CAT, GSH and GSH-Px.
7. 7. The method according to any one of claims 1 to 6, wherein said aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, is administered in a daily dose of 0.1-500 mg.
8. 8. The method according to any one of claims 1 to 7, wherein the aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, is administered in an amount of 0.1 μΜ to 1M or 0.001 to 50.0wt% (w/w).
9. 9. The method according to any one of claims 1 to 8, wherein the aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, is administered in an amount of 1 μm to 500 mM or 0.003 to 10% (w/w), or in a daily dose of 15-200 mg.
10. 10. The method of any one of claims 1 to 9, wherein the subject is a human, bovine or pet.
11. 11. The method according to any one of claims 1 to 10, wherein the composition is prepared as a food, beverage, supplement, cosmetic or skin care product.
12. 12. The method according to any one of claims 1 to 11, wherein the administration is by various routes selected from oral, intravenous, intramuscular, intraperitoneal, topical or sublingual applications.
13. 13. The method of any one of claims 1 to 12, wherein the composition is formulated as a solution, liquid suspension, injection, tablet, pill, granule, powder, film, suppository, capsule, aerosol, tonic, syrup, mask composition, functionalized cream composition, functionalized essence, skin care composition, cosmetic composition, or functionalized food composition.
14. 14. A composition comprising an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, for use in reducing or inhibiting advanced glycation end products (AGEs) in a subject.
15. 15. The composition of claim 14, wherein the composition is for anti-glycation.
16. 16. The composition according to claim 14 or 15, wherein the composition is for reducing or preventing aging.
17. 17. The composition of claim 16, wherein the aging is characterized by striae, loss of elasticity, orange-peel or dimness of the skin, reduced epidermis and dermis thickness, epidermal atrophy, reduced basal keratinocyte mitosis, reduced proliferative capacity, cellular aging, atrophy of the dermal extracellular matrix, altered physiological properties of connective tissue.
18. 18. The composition of any one of claims 14 to 17, wherein the reduction or inhibition of advanced glycation end products (AGEs) is achieved by scavenging chronic ROS, reducing H 2 O 2 and/or MMP-1 expression.
19. 19. The composition of claim 18, wherein said scavenging of chronic ROS comprises increasing the activity of antioxidant enzymes such as SOD, CAT, GSH and GSH-Px.
20. 20. The composition according to any one of claims 14 to 19, wherein said aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, is administered in a daily dose of 0.1-500 mg.

Description

Use of alisretinate for reducing or inhibiting advanced glycation end products Background Technical Field The present invention relates to compositions and methods for reducing or inhibiting advanced glycation end products (advanced glycation end products, AGEs) in a subject, particularly for anti-glycation, or reducing or preventing aging. The composition may comprise an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof. Background Advanced glycation end products (AGEs) are modifications of proteins or lipids that undergo non-enzymatic glycation and oxidation upon contact with aldoses. Early saccharification and oxidation processes result in the formation of Schiff base (Schiff base) and Amadori product (Amadori product). Further saccharification of proteins and lipids causes molecular rearrangements, leading to the production of AGEs. AGEs can fluoresce, generate Reactive Oxygen Species (ROS), bind to specific cell surface receptors, and form crosslinks. Or it may undergo further oxidation, dehydration, polymerization and oxidative decomposition reactions to produce many other AGEs. Oxygen, reactive Oxygen Species (ROS), and redox-active transition metals accelerate AGE formation. When an oxidation step is involved, the product is known as AGEs. The gradual accumulation of AGEs in the body can lead to a number of adverse effects, such as aging, in the hyperglycemic environment and during aging. AGEs can be caused by a variety of exogenous and endogenous causes. For exogenous reasons, ultraviolet irradiation is one of the most important exogenous reasons, which can induce oxidative stress and activation of Matrix Metalloproteinases (MMPs). The other is a higher carbohydrate dietary intake, inducing high glucose levels. A known mechanism for carbohydrates to cause oxidative stress is the activation of glucose mitochondrial oxidative metabolism, which leads to ROS production. For endogenous reasons, the main cause is the accumulation of oxidative damage caused by ROS with age. To date, there are synthetic inhibitors that can alleviate the development of AGEs, such as calcium antagonists, amlodipine, kinetin, quinine, and the like. However, these synthetic inhibitors have safety problems and side effects such as weakening of the liver, anemia, vomiting, gastrointestinal dysfunction, diarrhea, dizziness, headache and influenza. Thus, it can be appreciated that the importance and urgency of having a useful alternative to reduce or even inhibit the development of AGEs may be of great concern. Alisretinate (CAS 5300-03-8), C 20H28O2, is a vitamin A metabolite. Retinol is also a metabolite of vitamin a, has effective antioxidant activity, and can clear away chronic ROS, and prevent AGEs. In the present invention, it has surprisingly been found that aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue or derivative thereof, may be considered as a promising and attractive ingredient for attenuating the process of AGEs, thereby inhibiting glycation, alleviating or preventing aging. Disclosure of Invention In a first aspect, the present invention provides a method of reducing or inhibiting advanced glycation end products (AGEs) in a subject, the method comprising administering to the subject a composition comprising an effective amount of aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue, or derivative thereof. In some embodiments, the method is used to combat saccharification. In some embodiments, the method is used to reduce or prevent aging. In some embodiments, aging is characterized by fine lines, loss of elasticity, a skin orange peel or dull appearance, reduced epidermis and dermis thickness, reduced basal keratinocyte mitosis, reduced proliferation capacity, cellular aging, atrophy of the extracellular matrix of the dermis, and altered physiological properties of connective tissue. In some embodiments, reducing or inhibiting advanced glycation end products (AGEs) is achieved by scavenging chronic ROS, reducing H 2O2 and/or MMP-1 expression. In some embodiments, scavenging chronic ROS includes increasing the activity of antioxidant enzymes such as SOD, CAT, GSH and GSH-Px. In some embodiments, the aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue, or derivative thereof, is administered at a daily dose of 0.1-500 mg. In some embodiments, the aliskiric acid, or a pharmaceutically acceptable salt, hydrate, ester, analogue, or derivative thereof, is administered at a daily dose of 8-500 mg、10-300 mg、15-200 mg、20-100 mg、0.1-400 mg、0.5-300 mg、1-200 mg、2-200 mg、5-200 mg、10-200 mg、3-150 mg、10-150 mg、3-100 mg、10-100 mg、5-90 mg、8-80 mg、10-80 mg、15-70 mg、20-60 mg. In some embodiments, the daily dose is administered in divided doses or in single doses. In some embodiments, the administration is at least once a day or multiple times a day. In some embodiments, at leas