초록

The invention relates to the use of cocoa procyanidins in combination with an aspirin as an anti-platelet therapy and compositions comprising cocoa procyanidins and aspirin (acetylsalicyclic acid).

대표청구항 ▼

The invention relates to the use of cocoa procyanidins in combination with an aspirin as an anti-platelet therapy and compositions comprising cocoa procyanidins and aspirin (acetylsalicyclic acid). ring to the mammalian subject a composition comprising: a) a recombinagenic oligonucleobase, which

The invention relates to the use of cocoa procyanidins in combination with an aspirin as an anti-platelet therapy and compositions comprising cocoa procyanidins and aspirin (acetylsalicyclic acid). ring to the mammalian subject a composition comprising: a) a recombinagenic oligonucleobase, which comprises a first and a second homologous region, which regions are homologous with a target gene of a mammal, and a heterologous region, which is heterologous with the target gene and which contains an alteration, disposed between the first and the second homologous region; b) an aqueous carrier; and c) a macromolecular carrier selected from the group consisting of: (i) an aqueous-cored lipid vesicle, wherein the aqueous core contains the oligonucleobase, (ii) a lipid nanosphere, which comprises a lipophilic salt of the oligonucleobase, and (iii) a polycation having an average molecular weight of between 500 daltons and 1.3 Md wherein the polycation forms a salt with the oligonucleobase, wherein the macromolecular carrier further comprises a ligand for a clathrin-coated pit receptor, in an amount effective to alter the nucleotide sequence of the target gene in a number of cells in the subject to ameliorate the disease caused by the mutated sequence. 9. The composition of claim 2, in which the aqueous-cored lipid vesicle comprises dioleoylphosphatidylcholine and dioleoylphosphatidylserine. 10. The composition of claim 9, in which the aqueous-cored lipid vesicle further comprises a cerebroside. 11. The composition of claim 6, in which the recombinagenic oligonucleobase comprises at least 15 deoxynucleotides that are Watson-Crick base paired with 2'-Substituted Ribonucleotides. 12. The composition of claim 11, in which the 2'-Substituted Ribonucleotides are independently selected from the group consisting of 2'-methoxy-ribonucleotides, 2'-allyloxy-ribonucleotides, 2'-methoxyethoxy-ribonucleotides and 2'-fluoro-ribonucleotides. 13. The composition of claim 7, in which the clathrin-coated pit receptor is the asialoglycoprotein receptor. 14. The composition of claim 13, in which the ligand for the asialogylcoprotein receptor comprises a moiety selected from the group consisting of lactose, galactose, and N-acetylgalactosamine, and in which the sequence of the oligonucleobase comprises the sequence of a contiguous 16 nucleotide fragment of a mammalian gene that encodes a product selected from the group consisting of α1-antitrypsin, coagulation factor IX, uridinediphosphoglucuronate glucuronosyltransferase, glucocerebrosidase, glucose-6-phosphatase, low density lipoprotein receptor, ornithine transcarbamylase and phenylalanine hydroxylase, or the complement of the fragment. 15. A method of altering the nucleotide sequence of a target gene in a cell of a subject mammal comprising administering to the subject mammal the composition of claim 1 in an amount sufficient to alter the nucleotide sequence of the target gene in the cell of the subject mammal. 16. The method of claim 15, in which the cell is a liver cell. 17. The method of claim 15, in which: a) the first and the second homologous region are together at least 16 and not more than 60 nucleobases in length; and b) the heterologous region is at least 1 and not more than 20 nucleobases in length. 18. The composition of claim 1, in which the clathrin-coated pit receptor is the asialoglycoprotein receptor. 19. The method of claim 8, which further comprises the steps of determining the phenotypic effect of the altered target genes in the subject and subsequently increasing or decreasing said phenotypic effect by adjusting the number of said altered target genes in the subject. 20. The method of claim 8, which the cell is a hepatocyte. 21. The method of claim 18, in which: a) the first and the second homologous region are together at least 16 and not more than 60 nucleobases in length; and b) the heterologous region is at least 1 and not more than 20 nucleobases in length. 22. The method of claim 8, in which the target gene is an allele of a mammalian gene that encodes a product selected from the group consisting of α1-antitrypsin, coagulation factor IX, uridine