Gel composition and methods
First Claim
1. A method of systemically administering a beneficial agent to a subject which comprises implanting a system comprising a beneficial agent dissolved or dispersed substantially throughout a viscous gel, the system having a burst index of 8 or less.
0 Assignments
0 Petitions
Accused Products
Abstract
Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, compositions having burst indices of 8 or less for systemic applications and systems releasing 10% or less of the total dose of beneficial agent in the first 24 hours after implantation for local applications. The compositions include a biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.
-
Citations
63 Claims
- 1. A method of systemically administering a beneficial agent to a subject which comprises implanting a system comprising a beneficial agent dissolved or dispersed substantially throughout a viscous gel, the system having a burst index of 8 or less.
- 8. A method of locally administering a beneficial agent to a subject which comprises implanting a system comprising a beneficial agent dissolved or dispersed substantially throughout a viscous gel, the system releasing within 24 hours after implantation not greater than 20% by weight of the amount of beneficial agent to be delivered over the duration of the delivery period.
-
15. A method of administering a beneficial agent to a subject in a controlled manner approximating zero order release by implanting a gel composition comprising a biocompatible polymer, a biocompatible solvent having a solubility in water of less than 7%, and a beneficial agent, wherein the loading of the beneficial agent in the interior of the polymer is above that required to saturate the beneficial agent in water.
- 16. A method of administering a beneficial agent to a subject which comprises implanting a system comprising a beneficial agent dissolved or dispersed substantially throughout a viscous gel formed of a biocompatible polymer and a solvent having a solubility in water of 7% or less, and a solubility modulator of the beneficial agent, the system having a burst index of or less.
-
18. An implantable composition for the systemic delivery of a beneficial agent to a subject wherein the composition comprises a polymer;
- an amount of a solvent to form a viscous gel with the polymer, and a beneficial agent dissolved or dispersed in the gel, wherein the solvent comprises a single solvent or a mixture of solvents with at least one solvent having a miscibility in water of less than 7% by weight and the total amount of solvent constituting 40% or more by weight of the gel vehicle, said composition having a burst index of 8 or less.
- View Dependent Claims (59, 60)
-
19. An implantable, biodegradable composition for the sustained delivery of a beneficial agent to a subject wherein the composition comprises a polymer;
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
a beneficial agent dissolved or dispersed in the gel, wherein the solvent comprises a mixture of solvents with at least one solvent in the mixture having a miscibility in water of less than 7% by weight. - View Dependent Claims (20)
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
-
21. An implantable, biodegradable composition for delivery of a beneficial agent to a subject wherein the composition comprises a polymer;
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
a beneficial agent dissolved or dispersed in the gel, wherein the solvent comprises a single solvent or a mixture of solvents with at least one solvent having a miscibility in water of less than 7% by weight selected from lower alkyl and aralkyl esters of benzoic acid.
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
-
22. An implantable gel composition for delivery of a beneficial agent to a subject comprising:
-
A) a biocompatible polymer;
B) a biocompatible solvent, having miscibility in water of less than 7% by weight and capable of dissolving the polymer and forming a viscous gel;
said solvent being selected from the group comprising compounds having the following structural formula;
wherein R1 is lower alkyl, aryl or aralkyl and R2 is aralkyl or lower alkyl; and
R1 and R2 may be the same or different;
with the proviso that when R1 and R2 are each lower alkyl, the number of total carbon atoms represented by R1 and R2 combined is 4 or more;
C) a beneficial agent; and
, optionally, one or more of the following;
D) an emulsifying agent;
E) a pore former; and
F) a solubility modulator for the beneficial agent; and
G) an osmotic agent.
-
-
23. An implantable gel composition for delivery of a beneficial agent to a subject comprising:
-
A) a biocompatible lactic acid-based polymer;
B) a biocompatible solvent, having miscibility in water of less than 7% by weight and capable of dissolving the polymer and forming a viscous gel;
said solvent being selected from the group comprising compounds having the following structural formula;
wherein R1 is lower alkyl, aryl or aralkyl and R2 is aralkyl or lower alkyl; and
R1 and R2 may be the same or different;
with the proviso that when R1 and R2 are each lower alkyl, the number of total carbon atoms represented by R1 and R2 combined is 4 or more;
C) a beneficial agent; and
, optionally, one or more of the following;
D) an emulsifying agent;
E) a pore former;
F) a solubility modulator for the beneficial agent; and
G) an osmotic agent. - View Dependent Claims (24, 25)
-
-
26. A method of preparing an injectable depot gel composition comprising:
-
A) mixing a biocompatible polymer and a solvent having a miscibility in water of 7% or less selected from lower alkyl and aralkyl esters of benzoic acid to form a viscous gel;
B) dispersing or dissolving a beneficial agent, optionally associated with a solubility modulator, in an emulsifying agent to form a beneficial agent containing emulsifying agent; and
C) mixing the beneficial agent containing emulsifying agent with the viscous gel, said beneficial agent containing emulsifying agent forming a dispersed droplet phase in the viscous gel, and optionally, D) mixing one or more of a pore former and an osmotic agent with said viscous gel, to provide an injectable gel composition.
-
-
27. A gel composition for systemic administration comprising:
-
A) a biocompatible polymer;
B) a biocompatible solvent having a miscibility in water of less than 7%;
C) a beneficial agent selected from the group consisting of cDNA, DNA, peptides, proteins and fragments and derivatives thereof, and optionally, one or more of the following;
D) an emulsifying agent;
E) a pore former;
F) a solubility modulator for the beneficial agent; and
G) an osmotic agent. wherein the composition has a burst index of less than 8.
-
-
28. A kit for administration of a beneficial agent to a subject comprising:
-
A) a biocompatible polymer;
B) a solvent having a miscibility in water of 7% or less by weight that is suitable for dissolving the polymer and forming a viscous gel;
C) a beneficial agent; and
optionally, one or more of the following;
D) an emulsifying agent;
E) a pore former;
F) a solubility modulator for the beneficial agent, optionally associated with the beneficial agent; and
G) an osmotic agent;
wherein at least the beneficial agent, optionally associated with the solubility modulator, is maintained separated from the solvent until the time of administration of the beneficial agent to a subject.
-
-
29. An implantable composition for the systemic delivery of a beneficial agent comprising a poly(lactide-co-glycolide) copolymer;
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
a beneficial agent selected from the group consisting of cDNA, DNA, peptides, proteins and fragments and derivatives thereof, said composition having a burst index of equal to or less than 8.
- an effective plasticizing amount of a solvent to form a viscous gel with the polymer; and
-
30. An implantable composition for the sustained delivery of a beneficial agent comprising a poly(lactide-co-glycolide) copolymer;
- an effective plasticizing amount of a solvent comprising a lower alkyl or aralkyl ester of benzoic acid to form a viscous gel with the polymer; and
a beneficial agent. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48)
- an effective plasticizing amount of a solvent comprising a lower alkyl or aralkyl ester of benzoic acid to form a viscous gel with the polymer; and
- 61. An implantable gel composition comprising a biocompatible polymer, a biocompatible solvent forming a viscous gel with the polymer, and a beneficial agent, the composition imbibing 40% or less of its bulk weight in water within the first 21 days after implantation.
Specification