Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1997-04-21
1998-11-24
Azpuru, Carlos
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
514777, 264 41, 428402, A61K 950, B01J 1302, B32B 516, A01N 2512
Patent
active
058403418
DESCRIPTION:
BRIEF SUMMARY
RELATED APPLICATIONS
Priority is claimed under 35 U.S.C. .sctn.119 to PCT/GB95/01980, filed Aug. 21, 1995, which corresponds to GB 9416884.6, filed Aug. 20, 1994.
The present invention relates to drug delivery compositions and more particularly to compositions based on chitosan microparticles which provide for the improved uptake of active drug material across mucosal surfaces, such as the vagina, the small intestine, the colon, the lungs, the rectum, the eye, the buccal cavity or the nasal cavity.
BACKGROUND OF THE INVENTION
A major problem in drug delivery is the effective absorption of polar molecules, that include high molecular weight material such as proteins and peptides, across biological membranes. Normally such molecules are not well taken up by the body if administered to the gastrointestinal tract, the buccal mucosa, the rectal mucosa, the vaginal mucosa or the intranasal mucosa. By a polar molecule, we mean a substance that has an octanol/water partition coefficient of less than 50. Recent studies with insulin have demonstrated that the absorption of such a compound can be increased if it is given together with a so-called absorption enhancer. These absorption enhancing materials have included surfactants of the non-ionic type as well as various bile salt derivatives. An increased permeability of membranes in the presence of these types of surfactant materials is obtained and the literature in the field of pharmaceutical sciences contains a wide range of such absorption promoters. (For a review see Davis et al (editors), Delivery Systems for Peptide Drugs, Plenum Press, New York, 1987). However, such materials are sometimes unacceptable because of their irritant effects on membranes. These include not only the non-ionic variety of surface active agents but also bile salts and bile salt derivatives (eg fusidic acid).
European Patents 023,359A and 122,023A describe a powdery pharmaceutical composition for application to the nasal mucosa and methods for administration thereof. The pharmaceutical composition allows polypeptides and derivatives thereof to be effectively absorbed through the nasal mucosa. Similarly, U.S. Pat. No. 4,226,849 describes a method for administering a powdery medicament to the nasal mucosa where the preferred composition has mucoadhesive properties.
Formulations based on microspheres for mucosal delivery have been described in WO 88/09163. The formulations contain certain enhancers to aid effective penetration of the mucosa by the drug. WO89/03207 further describes formulations which do not require an enhancer.
WO 90/09780 describes a composition consisting of a drug and a polycationic substance including chitosan that promotes the transport of the drug across mucosal membranes. The composition can also comprise microspheres of the polycationic substance.
Chitosan is deacetylated chitin, or poly-N-acetyl-D-glucosamine. It is available from Protan Laboratories, Inc. Redmond, Wash. 98052, U.S.A. and, depending on the grade selected, can be soluble in water up to pH 6.0. Chitosan has previously been used to precipitate proteinaceous material, to make surgical sutures and as an immunostimulant. It has also been employed previously in oral drug formulations in order to improve the dissolution of poorly soluble drugs (Sawayanagi et al, Chem. Pharm. Bull., 31, 1983, 2062-2068) or for the sustained release of drugs by a process of slow erosion from a hydrated compressed matrix (Nagai et al Proc. Jt. US Jpn. Semin. Adv. Chitin. Chitosan. Relat. Enzymes, 21-39. Zikakis J. P. (ed), Academic Press. Orlando (1984)).
Chitosan microspheres have been produced for use for example for enhanced chromatographic separation (Li Q. et al, Biomater. Artif. Cells Immobilization Biotechnol, 21, 1993, 391-8) for topical delivery of drugs (Machida Y, Yakugaku Zasshi, 113, 1993, 356-68) for drug targeting after injection (Ohya Y et al, J. Microencapsul. 10, 1993, 1-9) and for controlled release of drugs (Bodmeier R. et al, Pharm Res. 6, 1989, 413-7, Chithambara et al J. Pharm. Pharmacol. 44, 1992,
REFERENCES:
patent: 5129877 (1992-07-01), Gallo et al.
Illum Lisbeth
Watts Peter James
Azpuru Carlos
Danbiosyst UK Limited
LandOfFree
Drug delivery composition containing chitosan or derivative ther does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Drug delivery composition containing chitosan or derivative ther, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Drug delivery composition containing chitosan or derivative ther will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1699446