Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Patent
1994-09-30
1996-11-05
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
424422, 424401, 424490, 424494, A61K 914
Patent
active
055715257
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
One of many known methods of achieving sustained delivery of a drug is by incorporating the drug in a solid polymeric matrix formed from a bioerodible polymer. Formulations of this type are primarily used for parenteral administration. The matrix may assume a variety of forms, but most often is either in the shape of thin rods suitable for injection, or microscopic particles suitable for application as a dry sprinkle or in a suitable liquid vehicle for injection.
The term "bioerodible" refers to the quality of the polymer that causes it to be degraded or eroded in vivo. This occurs either through enzymatic action or other types of action, and decomposes the polymer into biocompatible, non-toxic by-products which are further metabolized or excreted from the body through the normal physiological pathways, without raising an immunological reaction.
Among the wide variety of polymers having this quality, some which are of particular interest in this invention are poly(orthoester)s and poly(orthocarbonate)s. Such bioerodible polymers are disclosed in Schmitt, U.S. Pat. No. 4,070,347, Jan. 24, 1978; Choi, et al., U.S. Pat. No. 4,093,709, Jun. 6, 1978; Schmitt, U.S. Pat. No. 4,122,158, Oct. 24, 1978; Choi, et el., U.S. Pat. No. 4,131,648, Dec. 26, 1978; Choi, et al., U.S. Pat. No. 4,138,344, Feb. 6, 1979; Schmitt, U.S. Pat. No. 4,155,992, May 22, 1979; Choi, et al., U.S. Pat. No. 4,180,646, Dec. 25, 1979; Capozza, U.S. Pat. No. 4,322,323, Mar. 30, 1982; and Schmitt, U.S. Pat. No. 4,346,709, Aug. 31, 1982. The disclosures in these patents are incorporated herein by reference.
Other bioerodible polymers which are of interest in this invention are poly(lacticacid), poly(glycolic acid) and copolymers of lactic acid and glycolic acid. Published literature relevant to these polymers are Schmitt, et al., U.S. Pat. No. 3,991,766, issued Nov. 16, 1976; Yoles, S., et al., Polymer News 1(4/5):9-15 (1971); Kulkarni, R. K., et al., J. Biomed. Mater. Res. 5:169-181 (1971); and Wise, D. L., Acta Pharm. Suecica 13 (suppl.):34 (1976).
In Shih et al., Journal of Controlled Release 15:55-63 (Feb. 1990), "Acid Catalyzed poly(orthoester) Matrices for Intermediate Term Drug Delivery," the in vitro release of timolol maleate from poly(orthoester) matrices with lipophilic acid catalysts was studied.
In U.S. Pat. No 4,780,319 carboxylic acids are incorporated into polymers to catalyze the erosion of the polymer matrix. Poly(orthoesters), poly(orthocarbonates), polymers of ketenacetal and polyols, polyacetals, polyketals, polyacetates, polyglycolates and polycaprolactones are listed as the possible polymers.
In U.S. Pat. No. 4,346,709 erodible devices comprising a poly(orthoester) or poly(orthocarbonate), a drug and an erosion rate modifier are disclosed. The erosion rate modifiers can either increase or decrease the rate of erosion.
In these formulations in general, the drug is originally dispersed in and held immobile by the polymeric matrix, and the release of the drug from the matrix occurs gradually over a period of time. This sustained release is achieved by one or a combination of mechanisms, including diffusion of the drug through molecular interstices in the polymer, diffusion of the drug through pores in the polymer (if a pore-forming ingredient has been used in the formation of the polymer), and degradation of the polymer itself. The release rate may be controlled to a certain-degree by varying certain system parameters, such as the size and shape of the polymer systems, the choice of polymer used to form the matrix, the molecular weight and density of the polymer, the ratio of drug to polymer, the pore structure of the matrix, the inclusion of additional components such as erosion rate modifiers in the matrix, and the choice of carrier vehicle where one is used.
Degradation of the polymer is potentially the greatest contributing factor to the release of the drug, since degradation reduces and ultimately removes the diffusion barriers which retard the passage of the drug through the matrix. Also, th
REFERENCES:
patent: 3991766 (1976-11-01), Schmitt et al.
patent: 4070347 (1978-01-01), Schmitt
patent: 4093709 (1978-06-01), Choi et al.
patent: 4122158 (1978-10-01), Schmitt
patent: 4131648 (1978-12-01), Choi et al.
patent: 4138344 (1979-02-01), Choi et al.
patent: 4155992 (1979-05-01), Schmitt
patent: 4180646 (1979-12-01), Choi et al.
patent: 4322323 (1982-03-01), Capozza
patent: 4346709 (1982-08-01), Schmitt
patent: 4489056 (1984-12-01), Himmelstein et al.
patent: 4780320 (1988-10-01), Baker
patent: 4917892 (1990-04-01), Speaker et al.
patent: 4919939 (1990-04-01), Baker
patent: 4940588 (1990-07-01), Sparks et al.
patent: 4962091 (1990-10-01), Eppstein et al.
patent: 5008117 (1991-04-01), Calanchi et al.
patent: 5077049 (1991-12-01), Dunn et al.
patent: 5098443 (1992-03-01), Parel et al.
patent: 5194473 (1993-03-01), Shinoda et al.
WO,A,9 213 567 (Nova Pharmaceutical Corporation), 20 Aug. 1992.
Journal of Controlled release, vol. 15, No. 1, Feb. 1990, Amsterdam NL, pp. 55-63.
Shih, Lucas, Zeniner; Acid catalyzed poly(ortho ester matrices for intermediate term drug delivery.
Pharmazie, vol. 47, No. 6, 1992, Berlin DD, pp. 436-439, Thoma, Schlutermann, Beziehungen zwischen Herstellungsparametern und pharmazeutisch-technologischen Anforderungen an biodegradierbare Mikropartikel.
J. Heller, Biomaterials, 1990, vol. 11:659-661, "Development of poly (ortho esters): a historical overview".
Ehnow Fred
Roorda Wouter E.
ALZA Corporation
Dillahunty Mary Ann
Howard Sharon
Ito Richard T.
Page Thurman K.
LandOfFree
Erosion rate modifier for use in bioerodible drug delivery devic does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Erosion rate modifier for use in bioerodible drug delivery devic, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Erosion rate modifier for use in bioerodible drug delivery devic will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2013256