Method of Treating Hormonal Disorders Using Injectable Leuprolide
A method and system for treating a hormonal disorder comprising injecting a composition comprising an effective amount of leuprolide or a salt thereof to a patient suffering from the hormonal disorder, with the system comprising N-methylpyrrolidone (NMP) and a polymer having a weight average molecular weight between 5,000 and 50,000 Dalton, an acid number of less than 3 mgKOH/g.
1 . A method of treating a hormonal disorder comprising injecting a composition comprising an effective amount of leuprolide or a salt thereof to a patient suffering from the hormonal disorder, wherein prior to the injecting, the method comprises purifying a polymer having a weight average molecular weight between 5,000 and 50,000 Dalton and an acid number of less than 3 mgKOH/g to remove residual lactide monomers to a level of less than or equal to 0.3% by weight of the polymer, wherein the polymer is selected from the group consisting of polylactide (PLA) polymer, poly(lactide-co-glycolide) (PLGA), and a combination thereof; and combining the purified polymer with an organic solvent and the effective amount of leuprolide or a salt to obtain the composition, wherein the organic solvent is N-methylpyrrolidone (NMP), and the process is free of a step of adding an acid additive in making the composition.
2 . The method of claim 1 wherein the hormonal disorder is an advanced prostate cancer.
3 . The method of claim 1 wherein the composition contains less than 2.5% by weight of a lactide-leuprolide conjugate formed after having been stored at 37° C. over a period of 14 days.
4 . The method of claim 1 wherein the leuprolide or a salt thereof is leuprolide acetate or leuprolide mesylate.
5 . The method of claim 1 wherein the leuprolide or a salt thereof is leuprolide mesylate.
6 . The method of claim 1 wherein the polymer is polylactide (PLA) polymer.
7 . The method of claim 1 wherein the polymer is poly(lactide-co-glycolide) (PLGA) having the ratio of lactide/glycolide from 50/50 to 100/0.
8 . A process of making an injectable composition comprising:
combining a polymer having a weight average molecular weight between 5,000 and 50,000 Dalton, an acid number of less than 3 mgKOH/g and a content of residual lactide monomers in the polymer of less than about 0.3% by weight, wherein the polymer is selected from the group consisting of polylactide (PLA) polymer, poly(lactide-co-glycolide) (PLGA), and a combination thereof; with
an organic solvent; and
a leuprolide or a salt thereof;
wherein the process is free of a step of adding an acid additive in making the composition.
9 . The process of claim 8 wherein the polymer has the content of residual lactide monomers of less than about 0.2% by weight.
10 . The process of claim 8 wherein the polymer has the content of residual lactide monomers of less than about 0.1% by weight.
11 . The process of claim 8 wherein the polymer has an acid number of less than 2 mgKOH/g.
12 . The process of claim 8 wherein the polymer is poly(lactic acid).
13 . The process of claim 8 wherein the polymer is poly(lactide-co-glycolide) (PLGA) having the ratio of lactide/glycolide from 50/50 to 100/0.
14 . The process of claim 8 wherein the organic solvent is N-methyl-2-pyrrolidone.
15 . An injectable system for treating a hormonal disorder comprising:
a. a polymer having a weight average molecular weight between 5,000 and 50,000 Dalton, an acid number of less than 3 mgKOH/g, and a content of residual lactide monomers in the polymer of less than about 0.3% by weight, wherein the polymer is selected from the group consisting of polylactide (PLA) polymer, poly(lactide-co-glycolide) (PLGA), and a combination thereof;
b. an N-methyl-2-pyrrolidone; and
c. leuprolide or a salt thereof.
16 . The system of claim 15 wherein the polymer has an acid number of less than 2 mgKOH/g.
17 . The system of claim 15 wherein the content of residual lactide monomers in the polymer is less than about 0.2% by weight.
18 . The system of claim 15 wherein the content of residual lactide monomers in the polymer is less than about 0.1% by weight.
19 . The system of claim 15 wherein the polymer is poly(lactide) (PLA).
20 . The system of claim 15 wherein the polymer is poly(lactide-co-glycolide) (PLGA) having the ratio of lactide/glycolide from 50/50 to 100/0.