Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
2001-02-16
2003-06-10
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S422000, C424S423000, C424S426000, C424S484000, C424S486000, C424S499000, C514S002600, C514S772100
Reexamination Certificate
active
06576263
ABSTRACT:
BACKGROUND
A variety of approaches have been developed to permit the delivery of an active agent, such as a drug, to a subject, preferably for the sustained release of such agent. Such delivery systems are typically designed to protect the agent from the environment prior to delivery while permitting the controlled release of the agent to the targeted area of the subject.
A number of conventional controlled release systems are based on microstructures, such as liposomes, lipospheres, microcapsules, microparticles, and nanoparticles, as well as macrostructures, such as cylinders, discs, and fibers. Typically, an active agent, such as a drug, is blended with a polymer and then formed into the desired shape.
Many of such conventional systems cannot be used to form a solid implant with the structural integrity required for prosthetic applications. Furthermore, many of such systems cannot be used to form articles that can be infused with an active agent (e.g., drug) by a physician, for example, at the time of application to the subject. Also, many of such systems include polymers that cannot be easily controlled with respect to the rate of biodegradation and/or the rate of release of any incorporated active agents.
Hydrogels (e.g., a class of polymers that are swollen in an aqueous medium but do not dissolve in water) made by the crosslinking of albumin with polyethylene glycol (PEG) derivatives have been studied previously for possible drug delivery applications (D'Urso et al.,
Biotech. Tech.,
8, 71-76 (1994)). Another approach to the controlled delivery of drugs involves microencapsulation or microsphere formation with the use of synthetic bioabsorbable polymers such as poly(lactic acid) and various copolymers of lactide and glycolide. A drawback to the use of microspheres, however, is that they cannot be coated evenly and retained on the surface of a surgical site or on injured or diseased tissue. To address this problem, microsphere-containing membranes have been made by suspending the microspheres in a solution of a second polymer made with the use of a solvent that is a nonsolvent for the microspheres and then casting a film out of the mixture.
Thus, there is a need for other delivery systems, particularly for one that includes a polymer composition that can be varied to provide a range of biodegradation rates and delivery rates. Preferably, there is a need for a delivery system that includes a polymer composition that has sufficient structural integrity to be easy to handle.
SUMMARY
The present invention provides a preformed object for delivering an active agent to a subject, the preformed object being at least partially desolvated crosslinked albumin having a crosslinking agent of the formula:
I—(—X—LM—G)
n
wherein:
X is a difunctional polyoxyethylene chain portion or a bond;
LM is a difunctional linking moiety represented by the formulas —C(O)—, —(CH
2
)
b
C(O)— where b is an integer from 1 to 5, —C(O)—(CH
2
)
c
—C(O)— where c is an integer from 2 to 10 and where the aliphatic portion of the radical may be saturated or unsaturated, —C(O)—O—(CH
2
)
d
—O—C(O)— where d is an integer from 2 to 10, or an oligomeric diradical represented by the formulas —R—C(O)—, —R—C(O)—(CH
2
)
c
—C(O)—, or —R—C(O)—O—(CH
2
)
d
—O—C(O)— where c is an integer from 2 to 10, d is an integer from 2 to 10, and R is a polymer or copolymer having 1 to 10 monomeric lactide, glycolide, trimethylene carbonate, caprolactone or p-dioxanone fragments;
G is a leaving group selected from the group of N-oxysuccinimidyl, N-oxymaleimidyl, N-oxyphthalimidyl, nitrophenoxyl, N-oxyimidazolyl, and tresyl;
I is a multifunctional linking moiety derived from a multinucleophilic compound; and
n is an integer from 2 to 10;
with the proviso that when X is a difunctional polyoxyethylene chain portion —X—I—X— is PEG, which is a diradical fragment represented by the formula:
—O—(CH
2
—CH
2
—O—)
a
—
wherein a is an integer from 20 to 300.
Other embodiments of the present invention include such preformed objects with an active agent incorporated therein, which may or may not be resolvated, and such preformed objects having an active agent therein further incorporated into a secondary biodegradable matrix. Other embodiments include preformed objects of other biodegradable polymers having an active agent therein further incorporated into a secondary biodegradable matrix, which is of the chemistry described above for the preformed objects. Methods of making and methods of delivering an active agent to a subject are also provided by the present invention.
REFERENCES:
patent: 4101380 (1978-07-01), Rubinstein et al.
patent: 4250163 (1981-02-01), Nagai et al.
patent: 4349530 (1982-09-01), Royer
patent: 4839345 (1989-06-01), Doi et al.
patent: 4897268 (1990-01-01), Tice et al.
patent: 4898734 (1990-02-01), Mathiowitz et al.
patent: 4919939 (1990-04-01), Baker
patent: 4976968 (1990-12-01), Steiner
patent: 5302397 (1994-04-01), Amsden et al.
patent: 5470582 (1995-11-01), Supersaxo et al.
patent: 5508060 (1996-04-01), Perman et al.
patent: 5512268 (1996-04-01), Grinstaff et al.
patent: 5583114 (1996-12-01), Barrows et al.
patent: 5700476 (1997-12-01), Rosenthal et al.
patent: 5733563 (1998-03-01), Fortier
patent: 5759563 (1998-06-01), Yewey et al.
patent: WO 90/13540 (1990-11-01), None
patent: WO 93/00076 (1993-01-01), None
patent: WO 96/03159 (1996-02-01), None
patent: WO 99/66964 (1999-12-01), None
Weissleder, R. et al., “Quantitation of Slow Drug Release from an Implantable and Degradable Gentamicin Conjugate by In Vivo Magnetic Resonance Imaging,”Antimicrobial Agents and Chemotherapy, American Society for Microbiology, vol. 39, No. 4, Apr. 1995, pp. 839-845.
Bernatchez et al., “Sodium hyaluronate as a vehicle for an improved tolerance of 5-fluorouracil administered subconjunctivally to rabbits,”International Journal of Pharmaceutics, 106, pp. 161-166 (1994).
Liang et al., High-performance liquid chromatographic assay of cefazolin in rat tissues,Journal of Chromatography B: Biomedical Applications, 656, pp. 460-465 (1994).
Mathiowitz et al., “Bioadhesive Drug Delivery Systems,”Encyclopedia of Controlled Drug Delivery, vol. 1, pp. 9-45 (1999).
Bromberg et al., “Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery,”Advanced Drug Delivery Reviews, vol. 31, pp. 197-221 (1998).
Pendharkar et al., “Development of an Albumin Based Lung Sealant,”Society for Biomaterials, Sixth World Biomaterials Congress Transactions, p. 316 (2000).
Blum et al., “Effect of Material Composition on Shear Strength of an Adhesive Albumin,”Society for Biomaterials, Sixth World Biomaterials Congress Transactions, p. 106 (2000).
D'Urso et al., “New Hydrogel Based on Polyethylene Glycol Cross-Linked With Bovine Serum Albumin,”Biotechnology Techniques, vol. 8, No. 2, pp. 71-76 (1994).
Quirk et al., “Production of Recombinant Human Serum Albumin fromSaccharomyces cerevisiae,” Biotechnology and Applied Biochemistry, 11, 273-287 (1989).
Kalman et al., “Synthesis of a gene for human serum albumin and its expression inSaccharomyces cerevisiae,” Nucleic Acids Research, vol. 18, No. 20, pp. 6075-6081 (1990).
Sleep et al., “The Secretion of Human Serum Albumin From the YeastSaccharomyces CerevisiaeUsing Five Different Leader Sequences,”Bio/Technology, vol. 8, pp. 42-46 (1990).
Sijmons et al., “Production of Correctly Processed Human Serum Albumin in Transgenic Plants,”Bio/Technology, vol. 8, 217-221 (1990).
Abuchowski et al., “Cancer Therapy With Chemically Modified Enzymes,”Cancer Biochem. Biophys., vol. 7, pp. 175-186 (1984).
Ranade et al., “Role of Polymers in Drug Delivery,”Drug Delivery Systems, CRC Press, Inc., Boca Raton, FL, pp. 78-81 (1996).
Bernatchez Stephanie F.
Choi Hye-ok
Ferber Richard H.
Pournoor Kaveh
Truong Myhanh T.
Burtis John A.
Di Nola-Baron Liliana
Gram Christopher D.
Page Thurman K.
LandOfFree
Delivery systems using preformed biodegradable polymer... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Delivery systems using preformed biodegradable polymer..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Delivery systems using preformed biodegradable polymer... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3152533