Details for Patent: 6,020,320
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Title: | Acyl deoxyribonucleoside derivatives and uses thereof |
Abstract: | The invention relates to compositions comprising acyl derivatives of 2'-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced cellular damage, methods for improving wound healing and tissue repair, and methods for ameliorating the effects of aging comprising administering the compositions of the present invention to an animal. |
Inventor(s): | von Borstel; Reid Warren (Kensington, MD), Bamat; Michael Kevin (Chevy Chase, MD) |
Assignee: | Pro-Neuron, Inc. (Gaithersburg, MD) |
Filing Date: | Nov 17, 1993 |
Application Number: | 08/153,163 |
Claims: | 1. A method for enhancing the healing of skin wounds comprising administering to an animal in need thereof a wound-healing effective amount of a composition comprising acylated 2'-deoxyguanosine (II) and acylated 2'-deoxycytidine (III) having the structure: 2'-deoxyguanosine (II) ##STR12## 2'-deoxycytidine (III) ##STR13## wherein R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof. 2. A method for enhancing the healing of burned tissue comprising administering to an animal in need thereof a burned tissue-healing effective amount of a composition comprising acylated 2'-deoxyguanosine (II) and acylated 2'-deoxycytidine (III) having the structure: 2'-deoxyguanosine (II) ##STR14## ' -deoxycytidine (III) ##STR15## wherein R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof. 3. A method for enhancing the healing of diseased or damaged liver tissue comprising administering to an animal in need thereof an effective amount of a composition comprising acylated 2'-deoxyguanosine (II) and acylated 2'-deoxycytidine (III) having the structure: ' -deoxyguanosine (II) ##STR16## 2'-deoxycytidine (III) ##STR17## wherein R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof. 4. A method for enhancing the healing of bone marrow comprising administering to an animal in need thereof an effective amount of a composition acylated 2'-deoxyguanosine (II) and acylated 2'-deoxycytidine (III) having the structure: 2'-deoxyguanosine (II) ##STR18## 2'-deoxycytidine (III) ##STR19## wherein R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof. 5. A method as in claim 1 wherein said composition further comprises one or more of the acylated 2'-deoxyribonucleosides selected from the group consisting of: 2'-deoxyadenosine (I), ##STR20## 2'-deoxythymidine (IV) ##STR21## ' -deoxythymidine (V) ##STR22## wherein in the case of compounds I and IV, R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof, and in the case of compound (V), R" is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that the R" on nitrogen is not hydrogen, or the pharmaceutically salt thereof. 6. A method as in claim 2 wherein said composition further comprises one or more of the acylated 2'-deoxyribonucleosides selected from the group consisting of: 2'-deoxyadenosine (I), ##STR23## 2'-deoxythymidine (IV) ##STR24## 2'-deoxythymidine (V) ##STR25## wherein in the case of compounds I and IV, R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof, and in the case of compound (V), R" is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty,acid, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that the R" on nitrogen is not hydrogen, or the pharmaceutically salt thereof. 7. A method as in claim 3 wherein said composition further comprises one or more of the acylated 2'-deoxyribonucleosides selected from the group consisting of: 2'-deoxyadenosine (I), ##STR26## 2'-deoxythymidine (IV) ##STR27## ' -deoxythymidine (V) ##STR28## wherein in the case of compounds I and IV, R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof, and in the case of compound (V), R" is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that the R" on nitrogen is not hydrogen, or the pharmaceutically salt thereof. 8. A method as in claim 4 wherein said composition further comprises one or more of the acylated 2'-deoxyribonucleosides selected from the group consisting of: 2'-deoxyadenosine (I), ##STR29## 2'-deoxythymidine (IV) ##STR30## ' -deoxythymidine (V) ##STR31## wherein in the case of compounds I and IV, R is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid containing 2 or more carbon atoms, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that at least one R substituent is not hydrogen, or the pharmaceutically acceptable salt thereof, and in the case of compound (V), R" is H or an acyl group derived from a carboxylic acid selected from one or more of the group consisting of pyruvic acid, lactic acid, enolpyruvic acid, an amino acid, a fatty acid, lipoic acid, nicotinic acid, pantothenic acid, succinic acid, fumaric acid, p-aminobenzoic acid, betahydroxybutyric acid, orotic acid and carnitine, with the proviso that the R" on nitrogen is not hydrogen, or the pharmaceutically salt thereof. 9. A method as in claim 1 wherein R is acetyl and R"" is acetyl, propionyl or butyryl, with the proviso that at least one R or R"" is not hydrogen, or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 10. A method as in claim 2 wherein R is acetyl and R"" is acetyl, propionyl or butyryl, with the proviso that at least one R or R"" is not hydrogen, or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 11. A method as in claim 3 wherein R is acetyl and R"" is acetyl, propionyl or butyryl, with the proviso that at least one R or R"" is not hydrogen, or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 12. A method as in claim 4 wherein R is acetyl and R"" is acetyl, propionyl or butyryl, with the proviso that at least one R or R"" is not hydrogen, or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. |