IP Library Granted Patent US 10,857,166
Granted Patent B2
US 10,857,166 · App. 15/884,118 · Granted Dec 8, 2020

Flavonoid compositions and related methods

Inventors: Catherina C. Caballero-George (Panama, PA); Andres Rivera Mondragon (Panama, PA)
Assignee: INSTITUTO DE INVESTIGACIONES CIENTIFICAS Y SERVICIOS DE ALTA TECNOLOGIA (INDICASAT AIP)
A61K31/7016A61K31/216A61K31/7048A61K36/185A61P9/08A61P9/12A61K2236/15A61K2236/33
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Quick Facts
Patent No.
US 10,857,166
App. No.
15/884,118
Granted
Dec 8, 2020
Kind
B2
Abstract

Flavonoids that are isolated from plant material of the genus Cecropia can be used to perturb G-protein coupled receptors in a mammalian cell. In some instances, one or more flavonoids may interact with one or more of the G-protein coupled receptors to transiently increase the concentration of cytosolic calcium. Administration of the isolated flavonoids can be used to treat hypertension, to protect the integrity of blood vessels and related conditions.

Claims (30)

1. A method of perturbing G-protein coupled receptors in a mammalian cell selected from the group of an angiotensin II receptor, type 1, an angiotensin II receptor, type 2, and an endothelin receptor, type B, the perturbation comprising antagonizing an angiotensin II receptor, type 1, agonizing an angiotensin II receptor, type 2, and agonizing an endothelin receptor, type B, the method comprising:

obtaining a formulation by extracting components from a plant material of the genus Cecropia by contacting a first solvent consisting of alcohol to the plant material to obtain extracted components into the first solvent, the extracted components being further purified via chromatography to obtain the formulation, the formulation having two or more flavonoids, the two or more flavonoids in the formulation being selected only from the group consisting of isovitexin-2″-O-rhamnoside, isovitexin-2″-O-glucoside, isovitexin-2″-O-xyloside, isovitexin-O-xyloside, isoorientin-2″-O-xyloside, and mixtures thereof; and

contacting the mammalian cell with an effective amount of the formulation.

2. The method of claim 1 , wherein the one two or more flavonoids collectively (1) antagonize the angiotensin II receptor, type 1, (2) agonize the angiotensin II receptor, type 2, and (3) agonize the endothelin receptor type B.

3. The method of claim 1 , wherein perturbation of the G protein coupled receptors causes vasodilation in a mammalian subject administered the formulation.

4. The method of claim 1 , wherein the two or more flavonoids are between 0.3% and 15% of the formulation by weight.

5. The method of claim 1 , wherein the plant material is macerated prior to extracting the components from the plant material.

6. The method of claim 1 , wherein the plant material is from one or more plants of the species Cecropia obtusifolia.

7. The method of claim 1 , wherein the plant material is exclusively from aerial parts of the plant.

8. The method of claim 1 , wherein the two or more flavonoids are isovitexin-2″-O-xyloside and isovitexin-2″-O-rhamnoside.

9. The method of claim 1 , wherein the two or more flavonoids provide a synergistic effect on the one or more G-protein coupled receptors relative to each of the flavonoids alone.

10. The method of claim 1 , wherein the formulation consists essentially of the two or more flavonoids.

11. The method of claim 1 , wherein the formulation consists essentially of isovitexin-2″-O-xyloside and isovitexin-2″-O-rhamnoside.

12. A method for dilating a blood vessel in a mammalian patient, the method comprising:

obtaining a composition by extracting components from a plant material of the genus Cecropia by contacting a first solvent consisting of alcohol to the plant material to obtain extracted components into the first solvent, the extracted components being further purified via chromatography to obtain the composition, the composition having two or more flavonoids, the two or more flavonoids in the composition being selected only from the group consisting of isovitexin-2″-O-rhamnoside, isovitexin-2″-O-glucoside, isovitexin-2″-O-xyloside, isovitexin-O-xyloside, and isoorientin-2″-O-xyloside, and mixtures thereof;

administering an effective amount of the composition to a mammalian patient;

wherein administration of an effective amount of the composition causes dilation of a blood vessel.

13. The method of claim 12 , further comprising selecting the mammalian patient based on a diagnosis of (1) systemic hypertension or (2) an elevated risk of systemic hypertension.

14. The method of claim 12 , wherein the plant material is from one or more plants of the species Cecropia obtusifolia.

15. A method for dilating a blood vessel in a mammalian patient, the method comprising:

obtaining a composition by extracting components from a plant material of the genus Cecropia by contacting a first solvent consisting of alcohol to the plant material to obtain extracted components into the first solvent, the extracted components being further purified via chromatography to obtain the composition, the composition consisting essentially of isovitexin-2″-O-xyloside and isovitexin-2″-O-rhamnoside;

administering an effective amount of the composition to a mammalian patient;

wherein administration of an effective amount of the composition causes dilation of a blood vessel.

16. The method of perturbing one or more G-protein coupled receptors in a mammalian cell according to claim 1 , wherein the alcohol has from one to four carbons.

17. The method of perturbing one or more G-protein coupled receptors in a mammalian cell according to claim 1 , wherein the alcohol is methanol.

18. The method of perturbing one or more G-protein coupled receptors in a mammalian cell according to claim 1 , wherein extracting the components

further comprises washing the extracted components with a second solvent comprising dichloromethane.

19. The method of perturbing one or more G-protein coupled receptors in a mammalian cell according to claim 18 , wherein the second solvent further comprises an alkane.

20. The method of claim 1 , wherein contacting the mammalian cell comprises administrating the formulation to a subject, the contacting the mammalian cell causing vasculoprotective effects in the subject.

21. The method of claim 1 , wherein the formulation has each of the flavonoids selected from the group consisting of isovitexin-2″-O-rhamnoside, isovitexin-2″-O-glucoside, isovitexin-2″-O-xyloside, isovitexin-O-xyloside, and isoorientin-2″-O-xyloside, and no other flavonoids.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2018
From: CABALLERO-GEORGE, CATHERINA C.; RIVERA MONDRAGON, ANDRES
To: INSTITUTO DE INVESTIGACIONES CIENTIFICAS Y SERVICIOS DE ALTA TECNOLOGIA (INDICASAT AIP)
Reel/Frame 045745/0400 →
Continuity (2)
Provisional Application 62453928 · Feb 2, 2017
Related Publication 20180235990A1 · Aug 23, 2018