Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2001-01-19
2003-09-30
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C424S422000, C424S423000, C424S424000, C424S425000, C424S426000, C424S490000, C424S497000, C424S499000, C424S501000, C514S769000, C514S772000, C514S772300, C514S772500, C514S772700, C514S777000, C514S778000, C514S781000, C514S784000, C514S953000, C514S965000
Reexamination Certificate
active
06627600
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an implant made of compacted microparticles and a method of manufacturing the compacted microparticles. The invention also relates to a method of administering such compacted microparticles to a subject.
BACKGROUND ART
In the administration of drugs and in the diagnosis of disease it is desirable, if not necessary, to effect a controlled release of one or more substances within the living organism, in particular within a mammal, over an extended period of time.
Controlled release over an extended period of time, however, is not possible by conventional methods of administering drugs such as oral administration or direct injection of a drug. Rather than providing a controlled concentration of the drug over an extended period of time, these methods of administration lead to an immediate release of the drug into the body followed by a decline in the blood level of the drug over time. The immediate release of drug, followed by a decline in the blood level of the drug over time, is often not the most desirable method of administration. Treatment of a disease or condition is often more effective when the level of the drug in the blood can be maintained at a desired constant level for an extended period of time. Moreover, the immediate entry of a drug into a body may create a concentration of the drug beyond the capacity of the active centers to accept the drug and may also exceed the capacity of the metabolic and excretory mechanisms of the living organism. If the level of the drug remains elevated, tissues and/or organs may suffer detrimental effects.
Continuous controlled release of a drug over an extended period of time has significant clinical advantages as well. For example, when drug treatment must continue for an extended period of time, oral administration or direct injection requires the inconvenience of repeated administration. Furthermore, when the treatment requires repeat administration there is the possibility that the patient will forget or purposely not administer the drug. If a drug can be administered in a continuous, controlled release manner over an extended period of time the need for repeat administration is avoided.
To achieve a desired blood level of a drug over an extended period of time a variety of implants have been developed that, when administered to a patient, provide continuous, controlled release, long term delivery of a drug. These formulations include dosage forms intended for ingestion, injection, vaginal and uterine insertion, percutaneous application, and subcutaneous implants, for example.
The implants contain the active agent or drug in combination with a polymeric delivery system that controls release of the drug. The drug is physically entrapped in the polymer matrix and is released from the matrix by diffusion through the polymer or breakdown of the polymer matrix. Typically, the polymeric delivery system is a biocompatible, biodegradable polymer matrix. The polymer matrix is, however, not always biodegradable. When non-biodegradable implants are used surgical removal of the implant is necessary after the drug has been released.
A number of matrix materials gave been developed for controlled release of drugs including polymer matrix materials made of hydrogels, gelatin, cellulose, organopolysiloxane rubbers, polyurethanes, waxes, polyvinyl alcohol, poly glycolic acid, and polylactic acid, for example. Frequently the polymer matrix is a copolymer of lactic acid and glycolic acid (“PLGA”, polylactic glycolic acid). Drug is released from the PLGA matrix by the hydrolytic breakdown of the matrix. As the polymeric matrix breaks down the drug is released into the surrounding body fluids.
The rate of drug delivery is affected by a variety of variables including, for example, the choice of the polymer matrix, concentration of the drug in the matrix, size and shape of the implant, method of manufacturing the implant, surface area of the implant, and pore size.
Microparticles are an example of a sustained release formulation, wherein the drug is administered in connection with a polymeric delivery system. Microparticles are fine particles of drug physically entrapped in the polymer matrix. The microparticles can be prepared by a variety of methods such as the phase separation method, described in European Patent No. 52,510, or by preparing a water-in-oil emulsion as described in U.S. Pat. No. 4,652,441 to Okada et al. Typically, the particle size is in the range of 0.5 to 400 &mgr;m. The microparticles may be included in injections, oral preparations (powders, granules, capsules, tablets, etc.), nasal preparations, suppositories (e.g., rectal, vaginal) and so on. The drug is released in a controlled manner by degradation of the polymer matrix.
Microparticles are most commonly administered by injection. An injectable preparation of the microparticles is prepared by suspending the microparticles in a suitable fluid. Suspending microparticles in a suitable fluid, however, is problematic in that the microparticles often tends to flocculate or clump together. Thus, preparing the injectable suspension must be done properly and carefully and can be a very tedious process. In addition, material is often lost when the suspension of microparticles is drawn into the syringe. Yet another disadvantage of administering microparticles by injection is that the administration is associated with a “burst” or an immediate release of the drug over a short period of time, followed by a slower more uniform release. The burst precludes high core loading of the microparticles (the concentration of the active principal within the microparticles) because the burst increases with core loading. Therefore, in order to inject a certain amount of drug, one must inject a high quantity of material having a low core loading and, thus, a large volume of suspension fluid.
Subcutaneous implants are another example of a sustained release formulation, wherein the drug is administered in connection with a polymeric delivery system. Subcutaneous implants are solid bodies containing drug physically entrapped in a polymer matrix. The solid body is much larger than microparticles and is implanted under the patients skin either surgically or by sub-dermal injection using conventional implanting devices. The implants may have a variety of shapes including a film, rod, fiber, hollow cylinder, closed tube, and the like.
The subcutaneous implants are manufactured by first forming a mixture of the drug and polymer matrix and then forming the implant, of desired structural shape, by injection molding, compression molding, or extruding the resulting mixture to produce a solid, uniform, monolithic implant. The mixture of drug and polymer matrix is formed either by mixing the drug with the dry polymeric material in powdered form or by forming a solution or slurry of the drug and polymer and removing the solvent.
Subcutaneous implants, however, often do not provide continuous, uniform release of the drug and may exhibit a “burst” or a “dead phase” following administration. The “dead phase” is a period during which essentially no active ingredient is released.
Yet another implant device for continuous release of actives are osmotic mini-pumps. Osmotic mini-pumps are, however, expensive and require surgical implantation and removal.
The prior art discloses a number of delayed release polymer/drug formulations, including the following:
U.S. Pat. No. 3,887,699 to Yolles discloses an article for dispensing drugs prepared by dispersing a drug in a biodegradable polymeric material that can be formed into a solid shape. Drug is released when the drug migrates or exudes from the interior to the surface of the polymeric article and/or when the polymer degrades.
U.S. Pat. No. 4,351,337 to Sidman discloses a biocompatible, biodegradable implant device formed as a structure in which a drug or other releaseable substance to be delivered is physically contained by a poly-&agr;-amino acid.
U.S. Pat. No. 4,761,289 to Shalati et al. describes a method for preparing a susta
Ardana Bioscience Limited
Choi Frank
Hartley Michael G.
Winston & Strawn LLP
LandOfFree
Compressed microparticles for dry injection does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compressed microparticles for dry injection, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compressed microparticles for dry injection will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3005411