Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1997-12-02
1999-10-05
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424458, 424461, 424462, 424470, 424474, 424480, 424482, 424490, 424497, A61K 926, A61K 930, A61K 958, A61K 962
Patent
active
059620242
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a composition intended for peroral intake, providing controlled drug release in the lower gastrointestinal tract. The composition according to the invention is especially well suited for the treatment of intestinal inflammations, especially inflammatory bowel diseases.
The invention relates in particular to a composition which is in granule form and releases phenylmethylene-2,4-pentanedione compounds in the lower gastrointestinal tract. Phenylmethylene-2,4-pentanedione compounds have been described previously in the applicant's patent application EP 440324. Animal test models have shown that these compounds, in particular 3-(3-cyanophenyl)methylene-2,4-pentanedione, have an effect in preventing intestinal inflammations, which effect is based specifically on local action on the inflamed intestinal wall. Phenylmethylene-2,4-pentanediones are thus useful in the treatment of, for example, ulcerative colitis and Crohn's disease, in which inflammation is present both in the small intestine and in the colon.
The object of the invention is to develop a composition which transports the drug to the lower gastrointestinal tract, where the drug is released gradually.
A further object is to develop a composition which releases the drug gradually in the lower gastrointestinal tract, where the drug acts locally in diseases of the lower gastrointestinal tract.
A particular object is to develop a composition which transports the drug at least to the lower part of the small intestine (ileum) before the drug begins to be released, and from which composition the drug is released gradually in the colon so that the entire drug dose has been released at the time the composition has reached the lower part of the colon.
The composition according to the invention may contain as the active agent any drug the release of which is desirable locally in the lower gastrointestinal tract, in particular in the colon. In addition to phenylmethylene-2,4-pentanediones the active agent may consist, for example, of other drugs used for the treatment of an intestinal inflammation, such as corticoids, 5-aminosalicylic acid and its derivatives. The active agent may also consist of drugs which act systemically. For example, the active agent may consist of drugs which have the chemical structure or polypeptides. Their peroral administration is limited by hydrolysis caused by digestive enzymes. The amount of these enzymes in the colon is, however, small, and so polypeptides can be absorbed satisfactorily also when administered perorally, insofar as the drug dosage form transports them as far as the colon before their release.
The composition according to the invention is a peroral composition providing controlled release of a drug, the composition comprising a) a core comprising the drug and a drug release controlling agent and b) an enteric coating, in which composition the drug release controlling agent substantially consists of a pH-sensitive enteric polymer.
The composition is preferably in the form of granules, preferably enteric matrix granules coated with enteric film. However, the formulation according to the invention may also be an enteric matrix tablet coated with enteric film.
The term "lower gastrointestinal tract" means here the lower part of the small intestine (ileum) and the colon. The term "enteric coating" means here a coating surrounding the core, the solubility of the coating being dependent on the pH in such a manner that it prevents the release of the drug in the stomach but permits the release of the drug at some stage after the formulation has emptied from the stomach. The term "pH-sensitive enteric polymer" respectively means a polymer the solubility of which is dependent on the pH so that it is insoluble in the gastric juice but dissolves at some stage after the formulation has emptied from the stomach. The term "pH dissolution point" means the pH value in which the pH-sensitive enteric polymer substantially begins to dissolve.
Of the agent used in the core for controlling drug release, about 95-100%
REFERENCES:
patent: 5209933 (1993-05-01), MacFarlane et al.
patent: 5525354 (1996-06-01), Posti et al.
Rohm Pharma, Prospekt, "Eudragit L und S, Anwendung in der Arzneimittel-Herstellung", 1984.
Yamada Akiya et al. (Teikoku Seiyaku KK), "Oral Administration Preparation for Treating Ulcerative Colitis and Crohn's Disease", PN JP3034928 --910214, Database Patent Abstracts of Japan, vol. 15, No. 163 (C-826), Apr. 24, 1991.
Teikoku Hormone MGF, "Oral Prepn. For Therapy of Ulcerous Colitis and Crohn's Disease--Contains 5-Aminosalicylic acid or Salazosulphapyridine", Disease WPI, AN 91-090637, Week 9113, Feb. 14, 1991, Derwent Publications Ltd., London, GB.
Sucker H. et al., "Pharmazeutische Technologie", 1991, 356-358, Thieme Verlag, Stuttgart.
Lahdenpaa Esa Petteri
Marttila Esko Veikko
Marvola Martti Lauri Antero
Yrjola Reija Tuulikki
Orion-yhtyma Oy
Page Thurman K.
Spear James M.
LandOfFree
Peroral composition for controlled release in the lower gastroin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peroral composition for controlled release in the lower gastroin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peroral composition for controlled release in the lower gastroin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1168688