Title:  Treatment for joint inflammation

United States Patent:  6,432,937

Issued:  August 13, 2002

Inventors:  Hallgren; Roger (Dragontorpsvagen, SE)

Assignee:  Astra Aktiebolag (Sodertalje, SE)

Appl. No.:  011623

Filed:  February 12, 1998

PCT Filed:  December 16, 1997

PCT NO:  PCT/SE97/02124

371 Date:  February 12, 1998

102(e) Date:  February 12, 1998

PCT PUB.NO.:  WO98/27987

PCT PUB. Date:  July 2, 1998

The invention provides the use of a glucocorticoid substance which has a minimal systemic effect in the manufacture of a medicament for oral or rectal administration for non-topical use in the treatment of joint inflammation.

DETAILED DESCRIPTION OF THE INVENTION

The invention is preferably used to treat a human or non-human mammal who suffers from rheumatoid arthritis, peripheral oligoarthritis, peripheral arthropathies or spondyloarthropathy, especially ankylosing spondylitis, psoriatic arthropathy, reactive arthritides and sacroiliitis. It can also be used to treat human or non-human mammals suffering from conditions where the joint inflammation is associated with intestinal inflammation.

The non-human mammals which the invention can be used to treat include domestic mammals such as cats, dogs, horses, sheep and cows.

The glucocorticoid substance used in the present invention is preferably one which has a first pass metabolism of at least 90%. The first pass metabolism of a glucocorticoid substance may be measured using the method described by Andersson, P et al in Xenobiotica (1987) 17: 35-44.

More preferably the glucocorticoid substance is budesonide, rofleponide or a derivative thereof, belcomethasone dipropionate, beclomethasone monopropionate, ciclesonide, tipredane, flunisolide, triamcinolone acetonide or fluticasone propionate. Budesonide is particularly preferred.

The glucocorticoid substance is used non-topically and can be administered either orally or rectally. When administered orally, it is administered oesophageally, generally in the form of tablets, pills, capsules, syrups, powders or granules; when administered rectally, it is optionally in the form of suppositories or enemas.

It may be administered on its own or as a pharmaceutical composition in association with a pharmaceutically acceptable diluent, adjuvant or carrier. Particularly preferred are compositions not containing material capable of causing an adverse, e.g. an allergic reaction.

The glucocorticoid substance may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol, starches such as potato starch, corn starch or amylopectin, cellulose derivatives, a binder such as gelatine or polyvinylpyrrolidone, and a lubricant such as magnesium stearate, calcium stearate, polyethylene glycol, waxes, and/or paraffin, and then compressed into tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatine, talcum, and/or titanium dioxide. Alternatively, the tablet may be coated with a suitable polymer dissolved in a readily volatile organic solvent. The tablet preferably has an enteric coating to allow release of the glucocorticoid substance in the lower intestine. Suitable capsules may be prepared by using the methods described in EP-A-502092, WO 95/08323 or WO 97/27843.

For the preparation of soft gelatine capsules, glucocorticoid substance may be admixed with e.g. a vegetable oil or polyethylene glycol. Hard gelatine capsules may contain granules of the substance using either the above mentioned excipients for tablets, e.g. lactose, saccharose, sorbitol , mannitol, starches, cellulose derivatives or gelatine. Also liquid or semisolid formulations of the substance may be filled into hard gelatine capsules.

Liquid preparations for oral application may be in the form of syrups or suspensions, for example solutions containing the glucocorticoid substance, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol. Optionally such liquid preparations may contain colouring agents, flavouring agents, saccharine and carboxymethylcellulose as a thickening agent or other excipients known to those skilled in art.

Rectal enema formulations can be in the form of simple suspensions of the glucocorticoid substance in a pharmaceutically acceptable carrier or may be in the form of a rectal foam formulation, for example as described in EP-A-468555.

The glucocorticoid substance is preferably administered at a dosage of from 0.1 to 40 mg, more preferably from 0.5 to 20 mg, most preferably from 1 to 10 mg, either as a single dose or in divided doses from 2 to 4 times per day. The pharmaceutical composition for oral administration used in the present invention should preferably be prepared in such a way that the glucocorticoid substance is released in the lower part of the small intestine or the upper part of the large intestine. Preferably the composition should be prepared so that the substance is released in the lower third of the small intestine or the upper fourth of the large intestine.

Claim 1 of 15 Claims

What is claimed is:

1. A method for treating joint inflammation in a patient, the method comprising:

identifying a patient in need of treatment for joint inflammation; and

orally or rectally administering to the patient a glucocorticoid substance selected from the group consisting of budesonide, rofleponide, beclomethasone dipropionate, beclomethasone monopropionate, ciclesonide, tipredane, flunisolide, triamcinolone acetonide, and fluticasone propionate, wherein said glucocorticoid substance is released in tie lower part of the small intestine or the upper part of the large intestine, and wherein said glucocorticoid substance is administered in an amount that is therapeutically effective for the non-topical treatment of joint inflammation in the patient.
 

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