WO1992008451A1

WO1992008451A1 - Use of nabumetone for treatment of cancer pain

Info

Publication number: WO1992008451A1
Application number: PCT/EP1991/002119
Authority: WO
Inventors: Enzo Grossi
Original assignee: Dr. Lo. Zambeletti S.P.A.
Priority date: 1990-11-14
Filing date: 1991-11-07
Publication date: 1992-05-29
Also published as: GB9024794D0; AU8860991A

Abstract

The use of nabumetone in the manufacture of a medicament for the treatment of cancer pain.

Description

Use of nabumetone for treatment of cancer pain.

The present invention relates to a method for the treatment of cancer pain and to a compound for use in such method.

U.S. Patent 4420639 describes 4-(6'-methoxy-2*- naphthyl)butan-2-one (nabumetone) and its use in the treatment of rheumatic and arthritic conditions.

It has now been discovered that nabumetone also has potential therapeutic utility for treating cancer pain.

Accordingly, the present invention provides a method for treating cancer pain in human or non-human animals, which comprises administering an effective, non-toxic amount of nabumetone, to human or non-human animals suffering from cancer pain.

The present invention also provides the use of nabumetone in the manufacture of a medicament for use in the treatment of cancer pain.

In a preferred embodiment of the invention, nabumetone is administered in combination with other analgesics, particularly opiates.

A nabumetone medicament, for use in the treatment of cancer pain may be prepared by admixture of nabumetone with an appropriate carrier, which may contain a diluent, binder, filler, disintegrant, flavouring agent, colouring agent, lubricant or preservative in conventional manner.

Preferably, the medicament is in unit dosage form and in a form adapted for use in the medical or veterinarial fields. For example, such preparations may be in a pack form accompanied by written or printed instructions for use as an agent in the treatment of cancer pain.

The suitable dosage range for nabumetone depends on the severity of the cancer pain and on the condition of the patient. It will also depend, inter alia, upon the relation of potency to absorbability and the frequency and route of administratio .

Nabumetone may be formulated for administration by any route, and examples are oral, rectal, topical, parenteral, intravenous or intramuscular administration. Preparations may, if desired, be designed to give slow release of nabumetone.

The medicaments may, for example, be in the form of tablets, dispersible tablets, capsules, sachets, vials, powders, granules, lozenges, reconstitutable powders, or liquid preparations, for example solutions or suspensions, or suppositories.

The medicaments, for example those suitable for oral administration, may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycerine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable setting agents such as sodium lauryl sulphate.

Solid medicaments may be obtained by conventional methods of blending, filling, tabletting or the like. Repeated blending operations may be used to distribute nabumetone throughout those medicaments employing large quantities of fillers. hen the medicament is in the form of a tablet, powder, or lozenge, any carrier suitable for formulating solid pharmaceutical compositions may be used, examples being magnesium stearate, starch, glucose, lactose, sucrose, rice 5 flour and chalk. Tablets may be coated according to methods well known in normal pharmaceutical practice,* in particular with an enteric coating. The medicament may also be in the form of an ingestible capsule, for example of gelatin containing nabumetone if desired with a carrier or other 10 excipients.

Medicaments for oral administration as liquids may be in the form of, for example, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water

15 or other suitable vehicle before use. Such liquid medicaments may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel, hydrogenated

20 edible fats; emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; aqueous or non-aqueous vehicles, which include edible oils, for example almond oil, fractionated coconut oil, oily esters, for example esters of glycerine, or propylene glycol, or ethyl alcohol, glycerine,

25 water or normal saline; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid; and if desired conventional flavouring or colouring agents.

Nabumetone may also be administered by a non-oral route. In 30 accordance with routine pharmaceutical procedure, the medicaments may be formulated, for example for rectal ¹ administration as a suppository. They may also be _f formulated for presentation in an injectable form in an

*. aqueous or non-aqueous soluti.on, suspensi.on or emulsi.on i.n

35 a pharmaceutically acceptable liquid, e.g. sterile pyrogen-free water or a parenterally acceptable oil or a mixture of liquids. The liquid may contain bacteriostatic agents, anti-oxidants or other preservatives, buffers or. solutes to render the solution isotonic with the blood, thickening agents, suspending agents or other pharmaceutically acceptable additives. Such forms will be presented in unit dose form such as ampoules or disposable injection devices or in multi- dose forms such as a bottle from which the appropriate dose may be withdrawn or a solid form or concentrate which can be used to prepare an injectable formulation.

As mentioned hereinbefore, the effective dose of nabumetone depends on the severity of the cancer pain the condition of the patient and on the frequency and route of administration. A unit dose will generally contain from 20 to 2000 mg and preferably will contain from 30 to 1000 mg, in particular 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 750, 800 or 1000 mg. The composition may be administered once or more times a day for example 2, 3 or 4 times daily, and the total daily dose for a 70 kg adult will normally be in the range 100 to 3000 mg. Alternatively the unit dose will contain from 2 to 20 mg of nabumetone and be administered in multiples, if desired, to give the preceding daily dose.

Most preferably nabumetone compositions are in the form of 500 mg or 1000 mg swallow tablets.

The present invention further provides a pharmaceutical composition for use in the treatment of cancer pain which comprises an effective amount of nabumetone and a pharmaceutically acceptable carrier. Such compositions may be prepared in the manner as hereinbefore described.

Claims

1. The use of nabumetone in the manufacture of a medicament for the treatment of cancer pain.

5

2. A use according to claim 1 wherein the medicament is adapted for oral administration.

3. A use according to claim 1 wherein the medicament is 10 adapted for parenteral administration.

. A use according to claim 1 wherein the medicament is adapted for topical administration.

155. A use according to any one of claims 1 to 4 wherein the medicament is in unit dose form and contains from 20 to 2000 mg of nabumetone.

6. A use according to claim 1 or 2 wherein the medicament 0 is in the form of a swallow tablet containing 500 mg or 1000 mg of nabumetone.

7. A method for the treatment of cancer pain in human or non-human animals, which comprises administering an 5 effective, non-toxic amount of nabumetone to a sufferer in need thereof.

8. A method according to claim 7 wherein the nabumetone is in a form adapted for oral administration. 0

9. A method according to claim 7 wherein the nabumetone is in a form adapted for parenteral administration.

10. A method according to claim 7 wherein the nabumetone 5 is in a form adapted for topical administration.

11. A method according to claim 7 wherein the nabumetone is in unit dose composition containing from 20 to 2000 mg of nabumetone.

512. A method according to claim 7 wherein the nabumetone is in the form of a swallow tablet composition containing 500 mg or 1000 mg of nabumetone.

13. A pharmaceutical composition for use in the treatment 0 of cancer pain which comprises an effective amount of nabumetone and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition according to claim 13 which is adapted for oral administration. 5

15. A pharmaceutical composition according to claim 13 which is adapted for parenteral administration.

16. A pharmaceutical composition according to claim 13 0 which is adapted for topical administration.

17. A pharmaceutical composition according to claim 13 wherein the nabumetone is in unit dose composition containing from 20 to 2000 mg. 5 " 18. A pharmaceutical composition according to claim 13 wherein the nabumetone is in the form of a swallow tablet composition containing 500 mg or 1000 mg of nabumetone.