Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/16—Amides, e.g. hydroxamic acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/10—Dispersions; Emulsions
  • A61K9/127—Liposomes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

• the present invention relates to the treatment of arthritic and like complaints.
• rheumatoid arthritis is a chronic form of arthritis where many joints are affected and the inflammation is often such that gross deformity and immobility of the joint may result.
• Rheumatoid arthritis has, in the past, been treated, for example, with cortisone or with non-steroidal anti-inflammatory drugs.
• Cortisone is effective in combating inflammation but also carries with its use a high risk of dangerous side effects.
• Treatment with non-steroidal anti-inflammatory drugs (NSAID's) has often been found not to be as effective as desired to reduce inflammation.
• the most popular NSAID is aspirin which has to be used in very high doses e.g. 16-18 tablets per day.
• Desferrioxamine is an iron-chelating agent which has long been used in the treatment of iron poisoning and which has also been used extensively in the examination of iron metabolism in many diseases including rheumatoid arthritis. We are not aware, however, that the use of desferrioxamine to reduce the inflammation in the treatment of rheumatoid arthritis has ever been disclosed.
• the present invention provides a method of treatment of rheumatoid arthritic and like diseases involving joint inflammation, which comprises administering desferrioxamine in a therapeutically effective dosage over a prolonged period.
• the method of the invention may be applied to the treatment of non-specific monoarthritis and any other instances of joint inflammation caused by free iron catalysis.
• the method of the invention may also be applied to any other complaint which is induced by the occurrence of free iron, for example certain instances of myocardial infarction as recently suggested.
• the amount of desferrioxamine administered is suitably a therapeutically effective amount in the range of from 1 to 10 g per day, for example 1 to 5 g per day, suitably 2 to 3 g per day.
• the present invention also provides a pharmaceutical preparation suitable for intra-articular administration which comprises desferrioxamine in admixture or conjunction with a pharmaceutically suitable carrier.
• the present invention further provides a pharmaceutical preparation in the form of a pack which contains a support member together with a plurality of dosage forms comprising desferrioxamine, preferably enough for 3 weeks' supply.
• the amount of desferrioxamine present in each dosage form in a pack of the invention is in the range of from 1 to 10 g, e.g. in the range of from 1 to 5 g, conveniently 2 to 3 g.
• the amount of desferrioxamine may be different in each dosage form, for example a pack may comprise a set of dosage forms one containing 1 g of desferrioxamine, another 2 g of desferrioxamine and so on to 5 g, 7 g or 10 g of desferrioxamine.
• the desferrioxamine is suitably present in lyophilised powder form as desferrioxamine mesylate but may be in a liposome formulation.
• Desferrioxamine may be administered by any one of several routes.
• Administration intravenously, intraperitoneally, subcutaneously, intra-muscularly or intra- articularly by infusion solution are all suitable routes, intra-articular and subcutaneous infusion being preferred.
• Administration by infusion solution may be by continuous pump administration or administration in divided doses, i.e. twice or three times daily, daily, weekly or monthly.
• the active substance may be present in the infusion solution prior to the start of the administration or may be injected in as a "bolus" concentrate.
• Other routes of administration possible are via the skin or by the use of a liposome formulation.
• Administration via the skin may be by the transdermal "delivery system" (Alza Corporation) where medication externally applied by means of a special applicator reaches the affected joint by absorption through the skin.
• Direct topical administration may occur from once to four times daily by means of an ointment or cream containing desferrioxamine.
• Preparations containing desferrioxamine may in addition contain the usual carriers, excipients and auxiliaries.
• pH-regulating substances e.g. sodium phosphate and substances imparting isotonicity to the solutions, e.g. sodium chloride, may be present.
• the period of administration of desferrioxamine will vary depending on the severity of the disease, but is usually at least 5 days. In chronic cases the administration may occur initially over a period of 3 weeks to a month with the treatment being repeated at 3, 6 or 12 month intervals or sooner if chronic inflammation occurs or recurs. In instances of subcutaneous administration by infusion solution, it has been found satisfactory for the initial 3 week treatment to consist of continuous administration over several hours daily for 5 consecutive days, followed by no administration for 2 days and then repeat treatment for the following 5 days and so on.
• the above methods of administration are acceptable methods for introducing desferrioxamine into the body but cannot ensure that all of the active substance reaches the site of the free iron and ferritin stores in the reticuloendothelial stores. Also the most useful preparations, the infusion solutions, have to be made up shortly before use from lyophilised desferrioxamine powder because aqueous desferrioxamine solution is unstable over periods of longer than a week.
• the present invention also provides a method for the treatment of rheumatoid arthritis, wherein a pharmaceutical preparation comprising desferrioxamine as a liposome formulation is administered to the patient orally or parenterally.
• Liposomes are lipoid vesicles of varying sizes which encapsulate an active ingredient.
• the lipoid walls may comprise one or more lipid bi-layers. Suitable lipids are phospholipids; they may be used in pure form or in combination with other suitable substances.
• Desferrioxamine in aqueous solution may be incorporated into liposomes which have an avidity for the reticuloendothelial cells without apparent loss of stability.
• each liposome formulation may contain in the range of 0.1 to 12.5 mg of desferrioxamine.
• Desferrioxamine has been found to give a significant reduction in joint inflammation in patients suffering from rheumatoid arthritis without any apparent side- effects. It has also been found to give such results when used in conjunction with non-steroidal anti-inflammatory drugs without any apparent undesirable interactions. Desferrioxamine may thus be used as a replacement for or as a supplement to the non-steroidal anti-inflammatory drugs already used.
• the solvent used for the lipoid mixture was chloroform.
• the size of the liposomes was varied in certain cases from multilamellar liposomes to unilamellar liposomes by ultrasonication.

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Cited By (44)

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Citations (1)

• 1982
  • 1982-01-18 NZ NZ201010A patent/NZ201010A/en unknown
  • 1982-06-15 US US06/388,573 patent/US4397867A/en not_active Expired - Fee Related
  • 1982-06-16 PH PH27434A patent/PH18342A/en unknown
  • 1982-06-16 EP EP82105285A patent/EP0068314A1/fr not_active Withdrawn
  • 1982-06-17 IT IT8248659A patent/IT8248659A0/it unknown
  • 1982-06-18 JP JP57104083A patent/JPS5823619A/ja active Pending
  • 1982-06-18 BE BE0/208382A patent/BE893559A/fr not_active IP Right Cessation
  • 1982-06-18 ZA ZA824327A patent/ZA824327B/xx unknown

Patent Citations (1)

Non-Patent Citations (4)

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