Patent EA-004734-B1 (EA)
Title: Injectable naltrexone microsphere compositions and their use in reducing consumption of heroin and alcohol
Inventor: TICE THOMAS R
IPC: A61K47/34
Filed: 2000-04-08
Abstract: 1. A microsphere composition comprising naltrexone free base in an amount in the range of 15 to 50 weight %, poly (D, L-lactide) as a matrix, and less than about 3 weight % ethyl acetate, capable of providing a physiologically effective level of naltrexone to reduce the consumption of heroin and alcohol when administered intramuscularly in a mammal over a period of 28 days, at least 90 weight % of said microsphere composition comprising microspheres having a diameter in the range of 20 to 100 mkm. 2. A microsphere composition according to Claim 1, wherein said naltrexone is present in an amount in the range of 15 to 25 weight % and said poly (D, L-lactide) has an inherent viscosity in the range of about 0.3 to 0.4 dl/g. 3. A microsphere composition according to Claim 1, wherein said naltrexone is present in an amount in the range of 35 to 45 weight % and said poly (D, L-lactide) has an inherent viscosity in the range of about 1.0 to 1.1 dl/g. 4. A microsphere composition according to Claim 1, wherein said microspheres are coated with mannitol. 5. A microsphere composition according to Claim 1, wherein said poly (D, L-lactide) is a mixture of poly (D, L-lactide) of differing inherent viscosity. 6. A microsphere composition according to Claim 1, wherein said composition is a mixture of microspheres which differ in at least one of weight % of naltrexone or poly (D, L-lactide) of differing inherent viscosity. 7. A microsphere composition according to Claim 1, wherein said microspheres are prepared by introducing a solution of said naltrexone and poly (D, L-lactide) in ethyl acetate into an aqueous solution of poly (vinyl alcohol), isolating the resulting microspheres by extracting the ethyl acetate with water. 8. A microsphere composition comprising 35 to 45 weight % naltrexone and a poly (D, L-lactide) matrix capable of releasing in a human subject over a 4-week period from about 10 to 40% per week of the total naltrexone released, while maintaining a therapeutic dosage of at least about 1 ng/ml during said 4-week period. 9. A microsphere composition according to Claim 8, wherein only one week of said 4-week period has greater than about 20% of the total naltrexone released. 10. A formulation for injection comprising a microsphere composition according to Claim 1 and Claim 8, carboxymethylcellulose, and mannitol. 11. A syringe comprising a composition according to Claim 10. 12. A method for reducing the consumption of heroin and alcohol by a subject abusing at least one of heroin and alcohol, said method comprising: administering an effective dose of a microsphere composition according to Claim 1 in an amount to inhibit the consumption of heroin and alcohol intramuscularly, whereby the consumption of heroin and/or alcohol is reduced. 13. A method according to Claim 12, wherein said administering comprises a sample of from 2 to 4 ml. 14. A method for reducing the consumption of heroin and alcohol by a subject abusing at least one of heroin and alcohol, said method comprising: administering an effective dose of a microsphere composition according to Claim 1, which composition continues to release naltrexone for greater than 28 days at least an effective dose; prior to the level of naltrexone falling below an effective dose, administering a second dose of said microsphere composition, whereby the combination of said original effective dose and said second dose provide an effective dose of naltrexone for at least an additional 28 days; and repeating said administration to have naltrexone being released from both a prior administration of said microsphere composition and the lately administered microsphere composition to maintain said effective dose of naltrexone. 15. A method according to Claim 14, wherein said administering comprises a sample of from 2 to 4 ml. 16. A method for reducing the consumption of heroin and alcohol by a subject abusing at least one of heroin and alcohol, said method comprising: administering an effective dose of a microsphere composition according to Claim 8 in an amount to inhibit the consumption of heroin and alcohol intramuscularly, whereby the consumption of heroin and/or alcohol is reduced.