Procyanidin and nitric oxide modulator compositions

An article of manufacture adapted for human or veterinary administration comprising (i) a polymeric compound of formula Arn, or a pharmaceutically acceptable salt, derivative, or oxidation product thereof, in the amount effective to modulate nitric oxide (NO), and (ii) an additional NO-modulating agent, wherein An is 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 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 up optionally Y=Z=hydrogen;
• and
• the sugar is optionally substituted with A phenolic moiety via an ester bond;
• and wherein the effective amount has a therapeutic or prophylactic effect when the product is administered for an effective period of time.

An article of manufacture adapted for human or veterinary administration comprising (i) catechin, epicatechin or a polymeric compound of formula An, or a pharmaceutically acceptable salt, derivative, or oxidation product thereof, in the amount effective to modulate nitric, oxide (NO), and (ii) an additional NO-modulating agent, wherein An is of the formula:

• wherein
• n is an integer from 2 to 12, 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;
• and
• X, Y and Z arc 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.

A method of treating a human or a veterinary animal in need of a treatment with a nitric oxide (NO) or NO-synthase modulating composition comprising administering to the human or a veterinary animal a NO or NO-synthase modulating composition which comprises:

• (i) an effective amount of a compound selected from the group consisting of:
• epicatechin, catechin, a polymer of the formula An, and a pharmaceutically acceptable salt thereof:
• wherein
• n is an integer from 2 to 12, 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 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;
• and (ii) an additional NO or NO-synthase modulating agent.

A method of making an article of manufacture adapted for human or veterinary use comprising the step of:

• (i) preparing a composition comprising an effective amount of catechin, epicatechin or a polymeric compound of formula An:
• or a pharmaceutically acceptable salt, derivative, or oxidation product 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, 3-(α)-O-sugar, or 3-(β)-O-sugar;
• 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 7 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;
• and
• the sugar is optionally substituted with a phenolic moiety via an ester bond;
• (ii) packaging the composition prepared in step (i), and
• (iii) instructing, directing or promoting use of the article of manufacture for prophylactic or therapeutic treatment of a vascular or cardiovascular system.