TH76767A - Pharmaceutical formulas of 5,7,14-triacatetracyclose [10.3.1.02,11.04,9] -hexadeca-2 (11), 3,5,7,9-pentaine - Google Patents

Abstract

DC60 This invention is directed toward an oral controlled-release (CR) pharmaceutical dosage formulation of 5,8,14-triazate tricyclo[10.3.1.0x2,11.0x4,9]-hexadeca-2(11)3,5,7,9 pentain, 1 and its pharmaceutically acceptable salts, and the methods of their use to reduce nicotine dependence or to aid in cessation or reduction of tobacco use while minimizing nausea as an opposite effect. This invention also relates to a low-acting, immediate-release (IR) dosage formulation of which a stable formulation exhibits uniform distribution and drug activity (chemical formulation). 1 This invention is directed toward an oral controlled-release (CR) pharmaceutical dosage formulation of 5,8,14-triazate tricyclo[10.3.1.0x2,11.0x4,9]-hexadeca-2(11)3,5,7,9 pentain, 1 and its pharmaceutically acceptable salts, and the methods of their use to reduce nicotine dependence or to aid in cessation or reduction of tobacco use while minimizing nausea as an opposite effect. Tricyclo[10.3.1.02,11.04,9]-hexadeca-2(11)3,5,7,9-pentaine, 1 and its pharmaceutically acceptable salts and methods of use of them to reduce nicotine addiction or to aid in the cessation or reduction of tobacco use while reducing nausea as an opposite effect. The invention also involves a low-immediate-release (IR) drug mixture which is a stable formulation with uniform drug distribution and activity (chemical formula) 1

Claims (14)

1. A controlled-release dosage formulation suitable for administration to an individual, consisting of 5,8,14-triazatetra-cyclo[10.3.1.02,11.04,9]-hexadeca-2(11),3,5,7,9-pentaine or its pharmacologically acceptable salts, and the means for administration of such compound or salt to such individual at a rate less than approximately 6 mg/hour, where at least approximately 0.1 mg of such compound or its pharmacologically acceptable salt is administered over a 24-hour period. 2. Controlled-release dosage formulations of Patent 1, whereby the method for administering the pharmaceutically acceptable compound or its salt is included in coated matrix, multiparticulate, or multiparticulate tablets. 3. Controlled-release dosage formulations of Patent 2, where such matrix tablets or multiparticulate tablets contain a hydrophilic matrix. 4. Controlled-release dosage formulations of Patent 1, whereby the method for administration of the aforementioned pharmaceutically acceptable compound or its salt is included, are in the form of coated tablets. 5. Controlled-release dosage formulation of Patent 1, where the pharmaceutically acceptable salts are tartrate or citrate salts. 6. A controlled-release dosage formulation of Patent 1, where the individual is a human being. 7. An appropriate controlled-release dosage formulation for individual use shall consist of 5,8,14-triazatetra-cyclo[10.3.1.02,11.04,9]-hexadeca-2(11)3,5,7,9-pentaine or its pharmacologically acceptable salts and a pharmacologically acceptable carrier such that the dosage formulation, when administered to such individual, results in the maximum plasma concentration (Cmax) of such pentaine at the initial administration of such individual, which on average is between 10 and 80% of the corresponding Cmax determined for equivalent doses of such pentaine in an immediate-release tablet formulation. 8. An appropriate controlled-release dosage formulation for individual use, comprising 5,8,14-triazatetra-cyclo[10.3.1.02,11.04,9]-hexadeca-2(11)3,5,7,9-pentaine or its pharmacologically acceptable salts and a pharmacologically acceptable carrier, which, when administered to such an individual, results in a time for the maximum plasma concentration (Tmax) increased for such drug at the initial administration to such an individual by an average of 50% of the corresponding Tmax obtained for the equivalent dose of such pentaine in the form of an immediate-release round tablet. 9. Appropriate controlled-release dosage formulations for individual use comprising 5,8,14-triazatetra-cyclo[10.3.1.02,11.04,9]-hexadeca-2(11)3,5,7,9-pentaine or its pharmaceutically acceptable salts and a pharmaceutically acceptable carrier in which such pentaine dosage formulations are released at a rate of less than 6 mgA/hour in vitro when dissolution is tested in a USP-2 instrument until the time for 50% weight/weight dissolution of such drug is between approximately 1 and 15 hours. 10. Immediate-release dosage formulations suitable for individual use, comprising 5,8,14-triazatetra-cyclo[10.3.1.02,11.04,9]-hexadeca-2(11)3,5,7,9-pentaine or its pharmacologically acceptable salts and a pharmacologically acceptable filler, where the level of total reducing zinc carbohydrate is less than 20% by weight. 11. Immediate-release dosage forms of claim 10 where the filler contains from approximately 77% w/w to approximately 91% w/w and can be selected from a group consisting of mannitol, xylitol, sorbitol, microcrystalline cellulose, powdered cellulose, starch, pregelatinized starch, calcium carbonate, calcium phosphate dibasic, tribasic calcium phosphate, calcium sulfate, magnesium carbonate, magnesium oxide, polloxamer such as polyethylene oxide and hydroxypropylmethylcellulose. 12. Immediate-release dosage formulation of Patent 10, where the fillers are mannitol, calcium phosphate dibasic, and microcrystalline cellulose. 13. The use of any one of the controlled-release dosage forms of Patents 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 for the manufacture of drugs for reducing nicotine addiction or to aid in the cessation or reduction of tobacco use in individuals. 14. The use of any of the dosage forms of Patents 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 for the production of drugs for the treatment of select disorders or conditions of the following: ulcerative colitis, purulent necrosis, Crohn's disease, hypersensitive bowel syndrome, spatic dystonia, chronic pain, acute pain, sprouting abdominal dysentery, pauchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis (ALS), cognitive dysfunction, hypertension, insatiable hunger, anorexia, obesity, cardiac arrhythmias, hypergastric acid secretion, ulcers, pheochromocytoma, supranuclear paralysis dependent on and dependent on chemicals, nicotine dependent on or dependent on. Tobacco products, alcohol, benzodiazepines, barbiturates, opioids, or cocaine; headaches, migraines; cerebrovascular disease; traumatic brain injury (TBI); obsessive-compulsive disorder (OCD); Huntington's Korea psychosis; tardiphsy, hyperkinesia, dyslexia; schizophrenia; multiple necrotic dementia; age-related cognitive decline; epilepsy, including petitmal epilepsy; Alzheimer's disease (AD); Parkinson's disease (PD); attention deficit hyperactivity disorder (ADHD); and Touretes syndrome in individuals requiring treatment for these conditions.