Patent EA-003460-B1 (EA)
Title: Liquid polymeric compositions for controlled release of bioactive substances
Inventor: CHERN REY T
IPC: B32B5/00
Filed: 1999-03-18
Abstract: 1. A liquid polymeric composition for controlled release of hydrophobic bioactive substances comprising: (a) 1 to 30% of a hydrophobic bioactive substance; (b) 1 to 20% of a poly (lactide-co-glycolide) copolymer; wherein the weight ratio of the poly (lactide-co-glycolide) copolymer to the hydrophobic bioactive substance is 1:1 or less; and (c) a mixture of hydrophilic and lipophilic solvents wherein the volume ratio of the hydrophilic and lipophilic solvents is from about 80:20 to about 5:95. 2. A composition of Claim 1 wherein said bioactive substance is present in about 1 to 10%. 3. A composition of Claim 1 wherein said poly (lactide-co-glycolide) copolymer is present in about 1 to 10%. 4. A composition of Claim 1 wherein the ratio of said hydrophilic and lipophilic solvents is from about 65:35 to about 35:65. 5. A composition of Claim 1 which comprises: (a) 1 to 10% of a hydrophobic bioactive substance; (b) 1 to 10% of a poly (lactide-co-glycolide) copolymer, wherein the weight ratio of the poly (lactide-co-glycolide) copolymer to the hydrophobic bioactive substance is 1:1 or less; (c) a mixture of hydrophilic and lipophilic solvents wherein the volume ratio of the hydrophilic and lipophilic solvents is from about 65:35 to about 35:65. 6. A composition of Claim 1 which comprises: (a) 5 to 10% of a hydrophobic bioactive substance; (b) 5 to 10% of a poly (lactide-co-glycolide) copolymer, wherein the weight ratio of the poly (lactide-co-glycolide) copolymer to the hydrophobic bioactive substance is 1:1 or less; (c) a mixture of hydrophilic and lipophilic solvents wherein the volume ratio of the hydrophilic and lipophilic solvents is from about 65:35 to about 35:65. 7. A composition of Claim 1 wherein said bioactive substance is selected from fipronil, the avermectins, ivermectins, eprinomectin, milbemycins, nodulisporic acid and derivatives thereof, estradiol benzoate, trenbolone acetate, progesterone, and norethisterone. 8. A composition of Claim 1 wherein the ratio of lactide:glycolide of the poly (lactide-co-glycolide) copolymer is from about 95:5 to about 50:50. 9. A composition of Claim 1 wherein the ratio of lactide:glycolide of the poly (lactide-co-glycolide) copolymer is from about 75:25 to about 65:35. 10. A composition of Claim 1 wherein said hydrophilic solvent is selected from glycerol formal, glycofural, N-methyl pyrrolidone, 2-pyrrolidone, isopropylidene glycerol, di (propylene glycol) methyl ether, and mixtures thereof. 11. A composition of Claim 1 which comprises: (a) 5 to 10% of a hydrophobic bioactive substance; (b) 5 to 10% of a poly (lactide-co-glycolide) copolymer, wherein the ratio of lactide:glycolide of the poly (lactide-coglycolide) copolymer is from about 75:25 to about 65:35, and the weight ratio of the poly (lactide-co-glycolide) copolymer to the hydrophobic bioactive substance is 1:1 or less; (c) a mixture of glycerol formal and triacetin wherein the volume ratio of glycerol formal and triacetin is from about 65:35 to about 35:65. 12. A method for the controlled release of a hydrophobic bioactive substance in an animal, including human, which comprises injecting said animal with a liquid polymeric composition of Claim 1. 13. A liquid polymeric composition comprising: (1) about 1-30% of at least one bioactive substance; (2) about 1-20% of at least one biologically acceptable polymer, wherein the weight ratio of the polymer to the bioactive substance is 1:1 or less; and (3) at least one lipophilic solvent or a mixture of at least one hydrophilic solvent and at least one lipophilic solvent, wherein the volume ratio of the hydrophilic and lipophilic solvents is from about 80:20 to about 0:100, and/or wherein the lipophilic solvent is present in an amount of at least about 16.5% by weight. 14. A method for the controlled release of a hydrophobic bioactive substance in an animal, including human, which comprises injecting said animal with a liquid polymeric composition of Claim 13.