Stable active compound complex of salts of o-acetylsalicylic acid with basic amino acids and glycine
View Patent ↗The present invention relates to stable active compound complexes of salts of o-acetylsalicylic acid with basic amino acids and glycine, to a process for their preparation and to their use as medicaments.
1. An active compound complex consisting essentially of a salt of o-acetylsalicylic acid with a basic amino acid and glycine, wherein said active compound complex comprises about 10 percent by weight of glycine and the melting range of the active compound complex has an endothermal peak temperature of 148±2° C. and an exothermal peak temperature of 153±2° C., and wherein said active compound complex has a particle size distribution having a mean particle size of less than 100 μm.
2. The active compound complex according to claim 1 with lysine as the basic amino acid.
3. The active compound complex according to claim 1 with D,L-lysine as the basic amino acid.
4. A process for preparing an active compound complex as defined in claim 1 , comprising rapidly combining o-acetylsalicylic acid and a basic amino acid by stirring in water or a water-miscible organic solvent at a temperature of less than or equal to 40° C. to form a homogeneous mixture, cooling the homogeneous mixture to a temperature of from −5 to 10° C., adding acetone and glycine, continuing stirring for at least 1 hour to facilitate crystal formation, isolating the crystals and, during crystallization, maintaining a temperature of less than or equal to 5° C.
5. The process according to claim 4 , wherein the basic amino acid used is D,L-lysine monohydrate.
6. The process according to claim 4 , wherein the glycine is employed as a suspension.
7. The process according to claim 4 , wherein, prior to the addition of acetone, seed crystals are added.
8. The process according to claim 7 , wherein, after the addition of the seed crystals, the mixture is stirred at from 0 to 5° C. for 2 to 8 hours.
9. The process according to claim 4 , wherein the ratio of the molar equivalents of o-acetylsalicylic acid to amino acid in the reaction solution is from 1:1.05 to 1:1.2.
10. The process according to claim 4 , wherein during crystallization the stirring energy is not more than 0.1 W per liter of reaction medium.
11. The process according to claim 4 , wherein the process is carried out under sterile conditions.
12. An active compound complex obtainable by a process according to claim 4 .
13. A medicament comprising at least one active compound complex according to claim 1 or 12 .
14. The medicament according to claim 13 , wherein it is in a parenteral administration form.
15. The medicament according to claim 13 , wherein it is a preparation for injection and infusion in the form of a solution, suspension or emulsion.
16. The medicament according to claim 13 , wherein it is in an application form in which the active compound complex is present, separately from the solvent for injection or infusion, and the finished preparation for injection or infusion is prepared only shortly before the administration by mixing with the solvent.
17. The medicament according to claim 16 wherein water is employed as solvent for injection or infusion.
18. The medicament according to claim 13 for the intravenous, intra-arterial, intracardial, intraspinal, intralumbar, intramuscular, subcutaneous, intracutaneous or intraperitoneal administration.
19. A method for the treatment of arthritis, neuralgia, myalgia, and/or migraine, comprising administering an effective amount of an active compound complex according to claim 1 .
20. A method for the treatment of myocardial infarction, stroke, ischemic heart diseases, angina pectoris, bypass operations, PTCA and/or stent implantation, comprising administering an effective amount of an active compound complex according to claim 1 .
21. The medicament according to claim 16 , wherein the active compound complex is present as a lyophilisate or sterile powder.