Compositions for, and methods of, treating atherosclerosis

• US 6,998,417 B2
• Filed: 04/22/2002
• Issued: 02/14/2006
• Est. Priority Date: 04/02/1996
• Status: Expired due to Term

• Current Assignee: Mars Incorporated
• Original Assignee: Mars Incorporated
• Inventors: Romanczyk, Leo J. Jr., Schmitz, Harold H.
• Primary Examiner(s): SOLOLA, TAOFIQ A
• Application Number:
  US10/127,817
• Publication Number:
  US 20030113290A1
• Time in Patent Office: 1,394 Days
• Field of Search: 514/456, 549/400, 549/415
• US Class Current: 514/456
• CPC Class Codes: A23G 1/32 characterised by the composition containing organic or inorganic compounds
• CPC Class Codes: A23G 3/36 characterised by the composition containing organic or inorganic compounds
• CPC Class Codes: A23K 20/111 Aromatic compounds
• CPC Class Codes: A23K 50/40 for carnivorous animals, e.g. cats or dogs
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 311/32 2,3-Dihydro derivatives, e.g. flavanones
• CPC Class Codes: C07D 311/62 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
• CPC Class Codes: C07D 311/64 with oxygen atoms directly attached in position 8
• CPC Class Codes: C07H 17/06 Benzopyran radicals
• CPC Class Codes: C11B 5/0035 Phenols; Their halogenated and aminated derivates, their salts, their esters with carboxylic acids

Abstract

Disclosed and claimed are cocoa extracts, compounds, combinations thereof and compositions containing the same, such as polyphenols or procyanidins, methods for preparing such extracts, compounds and compositions, as well as uses for them, especially a polymeric compound of the formula A_n, wherein A is a monomer of the formula:

• • wherein n is an integer from 2 to 18, such that there is at least one terminal monomeric unit A, and one or a plurality of additional monomeric units;
  • R is 3-(α)—OH, 3-(β)—OH, 3-(α)—O-sugar, or 3-(β)—O-sugar;
  • bonding between adjacent monomers takes place at positions 4, 6 or 8;
  • a bond of an additional monomeric unit in position 4 has alpha or beta stereochemistry;
  • X, Y and Z are selected from the group consisting of monomeric unit A, hydrogen, and a sugar, with the provisos that as to the at least one terminal monomeric unit, bonding of the additional monomeric unit thereto (the bonding of the additional monomeric unit adjacent to the terminal monomeric unit) is at position 4 and optionally Y=Z=hydrogen;
  • the sugar is optionally substituted with a phenolic moiety, at any position on the sugar, for instance via an ester bond, and
  • pharmaceutically acceptable salts or derivatives thereof (including oxidation products).

Claims

1. A method of therapeutic or prophylactic treatment of atherosclerosis, thrombosis, heart attack, stroke or vascular circulation problems comprising administering to a subject in need thereof an effective amount of a polymeric compound of the formula A_n or a pharmaceutically acceptable salt thereof:

wherein

n is an integer from 2 to 18, such that there is at least one terminal monomeric unit A, and one or a plurality of additional monomeric units;

R is 3-(α

)—

OH, 3-(β

)—

OH;

bonding between adjacent monomers takes place at positions selected from the group consisting of 4, 6 and 8;

a bond of an additional monomeric unit in position 4 has alpha or beta stereochemistry;

X, Y and Z are selected from the group consisting of monomeric unit A, hydrogen, and a sugar, with the provisos that as to the at least one terminal monomeric unit, bonding of the additional monomeric unit thereto is at position 4 and optionally y=Z=hydrogen;

wherein the subject is a human or a veterinary animal.

2. The method of claim 1, wherein n is 2 to 12.

3. The method of claim 2, wherein the subject is a human.

4. The method of claim 1, wherein n is 3 to 12.

5. The method of claim 4, wherein the subject is a human.

6. The method of claim 1, wherein the adjacent monomers bind at positions 4→

6 or 4→

8.

7. The method of claim 2, wherein the adjacent monomers bind at positions (4β

→

6) or (4β

→

8).

8. The method of claim 4, wherein the adjacent monomers bind at positions (4β

→

6) or (4β

→

8).

9. The method of claim 1, wherein the polymeric compound is selected from the group consisting of:

dimer EC-(4β

→

8)-EC, dimer EC-(4β

→

6)-EC, trimer [EC(4β

→

8)]₂-EC, trimer [EC-(4β

→

6)₂-EC, tetramer [EC-(4β

→

8)₃-EC, pentamer [EC-(4β

→

8)₄-EC, and pentamer [EC-(4β

→

8)₃-EC-(4β

→

6)-EC, wherein EC is a monomeric unit epicatechin.

10. The method of claim 9, wherein the subject is a human.

11. The method of claim 9, wherein the subject is a veterinary animal.

12. The method of claim 10, wherein the human is at risk of atherosclerosis, thrombosis, heart attack, stroke or vascular circulation problems.

13. The method of claim 10, wherein the human is suffering from atherosclerosis.

14. The method of claim 1, wherein the polymeric compound is administered in the form of a cocoa extract.

15. The method of claim 1, wherein the polymeric compound is administered in the form of a cocoa extract fraction.

16. The method of claim 15, wherein the cocoa extract fraction comprises dimer EC-(4β

→

8) and/or dimer EC-(4β

→

6)-EC.

17. The method of claim 1, wherein the polymeric compound is administered in the form of a cocoa beverage comprising non-alkalized cocoa solids.

18. The method of claim 1, wherein the polymeric compound is administered in the form of a chocolate comprising non-alkalized cocoa solids or liquor.

19. The method of claim 1, wherein the polymeric compound is administered in the form of a chocolate comprising CP-cocoa solids in powder or liquid form.

20. The method of claim 1, wherein the polymeric compound is administered in the form of a pharmaceutical dosage form.

21. The method of claim 9, wherein the polymeric compound is administered in the form of a pharmaceutical dosage form.

22. The method of claim 1, wherein the polymeric compound is administered in the form of a tablet or capsule.