Claims for Patent: 5,707,648

Summary for Patent: 5,707,648

Title:	Transparent liquid for encapsulated drug delivery
Abstract:	There is provided a stable transparent multi-component composition useful for the delivery of water soluble active agents to animals. The compositions are formulated with a mixture of an oil phase, an aqueous phase, and a surfactant system, along with the active agent to be delivered to the animal. The compositions are specially formulated to be compatible with capsules such as gelatin and starch capsules. The aqueous phase of the compositions contains a substantial amount of polyethylene glycol and can optionally also contain a plasticizer. Preferred active agents are proteinaceous materials.
Inventor(s):	Yiv; Seang H. (Wilmington, DE)
Assignee:	LDS Technologies, Inc. (Boothwyn, PA)
Application Number:	08/406,935
Patent Claims:	1. A stable, transparent drug delivery composition suitable for storage and administration of biologically active materials, comprising: (a) a delivery composition comprising: (1) from about 1 to about 80 weight percent of a pharmaceutically acceptable oil phase; (2) from about 3 to about 98 weight percent surfactant; (3) from about 2 to about 60 weight percent polyethylene glycol; (4) from about 0.5 to about 15 weight percent water; and (b) a therapeutically effective amount of a biologically active material having an octanol:water partition coefficient of less than about 0.1; provided that the composition does not contain a mixture of cholesterol and phospholipid, and wherein the ratio of the polyethylene glycol to water is at least 2:1. 2. The drug delivery composition of claim 1 wherein the delivery composition further comprises at least one plasticizer comprising sorbitol, mannitol, or glycerin, said plasticizer being present in an amount of from about 0.5 to about 10 weight percent of the delivery composition. 3. The drug delivery composition of claim 2 wherein the drug delivery composition is contained in a capsule and the ratio of the polyethylene glycol to water is from about 4:1 to about 99:1, and said plasticizer comprises sorbitol, mannitol, or glycerin. 4. The encapsulated drug delivery composition of claim 3 wherein the capsule is a gelatin or starch capsule. 5. The encapsulated drug delivery composition of claim 4 wherein the active material comprises a protein, peptide, or polysaccharide. 6. The encapsulated drug delivery composition of claim 5 wherein the surfactant component is a mixture of surfactants comprising a low HLB surfactant, said low HLB surfactant having an HLB below 10 and a high HLB surfactant, said high HLB surfactant having an HLB above 10, and wherein the low HLB surfactant comprises a C.sub.9-13 monoglyceride. 7. The encapsulated drug delivery composition of claim 5 wherein the active material comprises a medicament which is selected from the group consisting of erythropoietin, insulin, a growth hormone, calcitonin, growth colony stimulating factors, RGD peptides, hematoregulatory peptides, collagenase inhibitors, angiotensin inhibitors, heparins, hypothalamic releasing peptides, tissue plaminogen activators, artial natriuretic peptides, tumor necrosis factor, vasopressin, a vasopressin antagonist, t-PA, vamprire bat plasminogen amplifier, urokinase, streptokinase, interferon and interleukin, in a biologically effective, therapeutic, non-toxic quantity. 8. The encapsulated drug delivery composition of claim 5 wherein the active material comprises a medicament which is selected from the group consisting of insulins, growth hormones, fibrinogen antagonists and calcitonins. 9. A stable, transparent delivery composition, comprising: (a) from about 5 to about 70 weight percent of a pharmaceutically acceptable oil phase; (b) from about 10 to about 80 weight percent surfactant; (c) from about 5 to about 60 weight percent of an aqueous phase comprising from about 60 to about 95 weight percent polyethylene glycol, from about 2 to about 30 weight percent water, and from about 1 to about 15 weight percent plasticizer comprising sorbitol, mannitol, glycerin, sucrose, fructose, glucose, or lactose; and wherein the ratio of the polyethylene glycol to water is at least 2:1, provided that the composition does not contain a mixture of cholesterol and phospholipid. 10. The delivery composition of claim 9 wherein the polyethylene glycol to water ratio is from about 4:1 to about 99:1, and said plasticizer comprises sorbitol, mannitol, or glycerin. 11. The delivery composition of claim 10 wherein the aqueous phase consists of said water, polyethylene glycol, and plasticizer. 12. The delivery composition of claim 11 further comprising a therapeutically effective amount of a biologically active, therapeutic material having an octanol:water partition coefficient of less than 0.1. 13. The drug delivery composition of claim 12 wherein the drug delivery composition is contained in a hard gelatin, soft gelatin, or starch capsule. 14. The encapsulated drug delivery composition of claim 13 wherein the biologically active material comprises a protein, peptide, or polysaccharide. 15. The encapsulated drug delivery composition of claim 14 wherein the surfactant component is a mixture of surfactants comprising a low HLB surfactant, said low HLB surfactant having an HLB below 10 and a high HLB surfactant, said high HLB surfactant having an HLB above 10, and wherein the low HLB surfactant comprises a C.sub.9-13 monoglyceride. 16. The encapsulated drug delivery composition of claim 14 wherein the active material comprises a medicament which is selected from the group consisting of erythropoietin, insulin, a growth hormone, calcitonin, growth colony stimulating factors, RGD peptides, hematoregulatory peptides, collagenase inhibitors, angiotensin inhibitors, heparins, hypothalamic releasing peptides, tissue plaminogen activators, artial natriuretic peptides, tumor necrosis factor, vasopressin, a vasopressin antagonist, t-PA, vamprire bat plasminogen amplifier, urokinase, streptokinase, interferon and interleukin, in a biologically effective, therapeutic, non-toxic quantity. 17. The encapsulated drug delivery composition of claim 14 wherein the active material comprises a medicament which is selected from the group consisting of insulins, growth hormones, fibrinogen antagonists and calcitonins. 18. The encapsulated drug delivery composition of claim 14 wherein the oil is selected from the group consisting of triglycerides having from 21 to 45 carbon atoms and propylene glycol diesters having from 15 to 40 carbon atoms. 19. A method of administering an encapsulated drug delivery composition, comprising: providing a capsule within which is contained a drug delivery composition comprising: (a) a delivery composition comprising: (1) from about 5 to about 70 weight percent of an oil phase; (2) from about 5 to about 60 weight percent of an aqueous phase consisting essentially of water, polyethylene glycol, and at least one plasticizer, said aqueous phase comprising from about 2 to about 30 weight percent water, from about 60 and 95 weight percent polyethylene glycol, and from about 1 to about 15 weight percent plasticizer comprising sorbitol, mannitol, or glycerin; (3) from about 15 to about 75 weight percent of a surfactant mixture; and (b) a therapeutically effective amount of a biologically active therapeutic material having an octanol:water partition coefficient of less than about 0.1; and provided that the delivery composition does not contain a mixture of cholesterol and phospholipid; and administering said encapsulated drug delivery composition either orally, rectally, or vaginally to the body of an animal. 20. The method of claim 19 wherein said active material is either a protein, peptide, or polysaccharide. 21. The method of claim 20 wherein said administration is oral. 22. The method of claim 21 wherein the weight ratio of polyethylene glycol to water in said delivery composition is from 4:1 to 99:1. 23. The encapsulated drug delivery composition of claim 6 wherein said low HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition and said high HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition. 24. The encapsulated drug delivery composition of claim 23 wherein said delivery composition comprises from about 15 to about 55 weight percent polyethylene glycol. 25. The encapsulated drug delivery composition of claim 5 wherein said surfactant mixture comprises from 15 to 75 weight percent of said delivery composition. 26. The encapsulated drug delivery composition of claim 25 provided that said plasticizer does not comprise propylene glycol. 27. The encapsulated drug delivery composition of claim 7 provided that said plasticizer does not comprise propylene glycol. 28. The encapsulated drug delivery composition of claim 24 provided that said plasticizer does not comprise propylene glycol. 29. The encapsulated drug delivery composition of claim 15 wherein said low HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition and said high HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition. 30. The encapsulated drug delivery composition of claim 29 wherein said aqueous phase comprises from about 70 to about 90 weight percent polyethylene glycol, and the ratio of the polyethylene glycol to water is from about 5:1 to about 95:5. 31. The encapsulated drug delivery composition of claim 14 provided that said plasticizer does not comprise propylene glycol. 32. The encapsulated drug delivery composition of claim 16 provided that said plasticizer does not comprise propylene glycol. 33. The encapsulated drug delivery composition of claim 29 provided that said plasticizer does not comprise propylene glycol. 34. The method of claim 22 wherein the surfactant component of said delivery composition is a mixture of surfactants comprising a low HLB surfactant, said low HLB surfactant having an HLB below 10 and a high HLB surfactant, said high HLB surfactant having an HLB above 10, and wherein the low HLB surfactant comprises a C.sub.9-13 monoglyceride. 35. The method of claim 34 wherein said low HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition and said nigh HLB surfactant is present in an amount of from about 10 to about 40 weight percent of said delivery composition. 36. The method of claim 35 wherein the active material comprises a medicament which is selected from the group consisting of erythropoietin, insulin, a growth hormone, calcitonin, growth colony stimulating factors, RGD peptides, hematoregulatory peptides, collagenase inhibitors, angiotensin inhibitors, heparins, hypothalamic releasing peptides, tissue plaminogen activators, artial natriuretic peptides, tumor necrosis factor, vasopressin, a vasopressin antagonist, t-PA, vamprire bat plasminogen amplifier, urokinase, streptokinase, interferon and interleukin, in a biologically effective, therapeutic, non-toxic quantity. 37. The method of claim 35 wherein the drug delivery composition is contained in a hard gelatin, soft gelatin, or starch capsule. 38. The method of claim 22 provided that said plasticizer does not comprise propylene glycol. 39. The method of claim 35 provided that said plasticizer does not comprise propylene glycol. 40. The drug delivery composition of claim 1 wherein the biologically active material comprises desmopressin. 41. The drug delivery composition of claim 3 wherein the biologically active material comprises desmopressin. 42. The drug delivery composition of claim 9 wherein the biologically active material comprises desmopressin. 43. The drug delivery composition of claim 10 wherein the biologically active material comprises desmopressin. 44. The method of claim 19 wherein the biologically active material comprises desmopressin. 45. The method of claim 44 wherein the administration is oral.

Details for Patent 5,707,648

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2015-01-13
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2015-01-13
Emergent Biosolutions Canada Inc.	BAT	botulism antitoxin heptavalent (a, b, c, d, e, f, g) - (equine)	Solution	125462	03/22/2013		2015-01-13