EP0245368A1 - Treatment of demyelinating diseases - Google Patents
Treatment of demyelinating diseasesInfo
- Publication number
- EP0245368A1 EP0245368A1 EP86906690A EP86906690A EP0245368A1 EP 0245368 A1 EP0245368 A1 EP 0245368A1 EP 86906690 A EP86906690 A EP 86906690A EP 86906690 A EP86906690 A EP 86906690A EP 0245368 A1 EP0245368 A1 EP 0245368A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- disease
- colchicine
- treatment
- active ingredient
- progression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
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
Definitions
- This: invention relates to the treatment of demyelinating diseases f particularly multiple sclerosis (MS), with colchicine or_ colchiceine.
- MS multiple sclerosis
- Demyelinating diseases of central or peripheral origin are diseases which destroy myelin which is a substance compounded principally of fats and proteins. It is wrapped in numerous thin layers around nerve fibers where it acts as an insulator and speeds the transmission of messages along the nerve fibers. These afflictions include for example MS, Guillain-Barre syndrome and polymyositis. Of these, MS is by far the most prevalent. This invention will be described principally as it relates to MS.
- MS is a disease of profound suffering and pervasive disability, the etiology of which remains unknown despite intensive investigation. It consists of patches or plagues of damaged myelin scattered throughout the central nervous system resulting from demyelination and subsequent scar formation.
- multiple sclerosis describes the fact that in this disease there are many damaged areas filled with sclerotic (scar) .tissue. Over a long period, new scar tissue may develop or old ones enlarge. The result is progressive degeneration of the nervous system resulting in progressive debilitation of the afflicted individual.
- SL'_ OSTITUTE SHEET MS significantly affects the most productive human age group (20-40 yrs). There are close to a million victims in the United States alone. The chief consequence of the disease is increasing deterioration of neurological function. Most victims are confined to wheelchairs or bed after 10 years. The prevalence ranges from 50/100,000 in the United States to 200/100,000 in Canada, Northern Great Britain, parts of France, Scandinavia and Russia.
- ACTH has been of some benefit in promoting remission of acute attacks, but has not been shown to modify the overall course of the disease.
- Combination therapy with ACTH and cyclophosphamide have shown some promise in temporarily halting the progression of severe MS.
- the work is very recent, and no final conslusion has been possible.
- Copolymer-I a synthetic polypeptide resembling myelin basic protein has shown some benefit, but these results are also too recent for proper evaluation.
- Colchicine is (S)-N-(5,6,7,9-tetrahydro-9-oxabenzo [a] heptaten-7-yl) acetamide. It has long been known as a therapeutic agent for humans, particularly as a gout suppressant and in the treatment of Familial Mediterranean Fever. It may be safely administered both orally and parenterally. Its activity in the mammalian body is well known and understood. Colchiceine is the 10- demethylated homolog of colchicine. It has also been used for the same purposes. Colchicine is the preferred therapeutic agent for the known utilities. It is also the preferred agent for use in this invention because it is readily available at reasonable cost and is extremely effective in retarding the progression of MS.
- colchicine and colchiceine may be administered to humans to treat demyelinating diseases, such as MS by retarding the process of demyelination. It is most convenient to administer the therapeutic agent orally, but parenteral administration including intravenous or intramuscular injection may also be employed.
- An effective dose for treating the disease will vary with a number of factors well known and understood by the physician. These include, for example, age and weight of the patients and the status of the disease.
- SHEET may vary from about .02 to .04 mg/kg of body weight per day.
- the required dosage will be administered once a day in a sustained release doage unit which may contain 1.2 to 2.4 mg of active compound as the principal active ingredient.
- a sustained release doage unit which may contain 1.2 to 2.4 mg of active compound as the principal active ingredient.
- Another convenient dosage unit is a scored tablet, each tablet containing 0.2 to 0.4 mg of active agent per scored segment. Such tablets are particularly useful since they permit the physician to investigate a large number of dosage regimens and titrate the optimum effective dosage for an individual patient.
- the oral and parenteral dosage units will be prepared in accordance with standard procedures and will contain the selected active compound as the only or principal active ingredient in the composition.
- Any of a wide variety of known inert excipients may be employed to prepare compositions useful in the practice of this invention. These include, for example, dextrose, starch, talc, various types of clay, mineral oil, cottonseed or sesame oil, as well as water or various miscible and immiscible aqueous compositions in which the therapeutic agent is soluble or may be suspended with the aid of known surfactants.
- the active ingredient can be formulated in tablet form with water soluble binding agents such as lactose or other palatable carbohydrates.
- SUBSTITUTE SHEET For rectal administration suppositories or inserts containing the active ingredient dispersed in such reagents as cocoa butter, petroleum, or other natural lubricants or in a synthetic emmollient such as polyethylene glycol 1000 or polyethylene glycol 4000 may be used.
- Transdermal administration will normally be from sustained release preparation which may be applied as a patch or. from a gauze applied to the skin.
- the preferred method of administering the active agents of this invention is from sustained release dosage forms since this is most convenient for patients, and avoids the necessity of constant clock watching or interruption of normal daily activities.
- a number of compositions suitable for such preparations are known and can be usefully employed.
- One convenient procedure is to formulate the selected motility control agent in a time disintegrating tablet or pellet coated with various thicknesses of known materials such as carnauba wax, cellulose esters and ethers, fats, keratin, gluten or various natural or synthetic esters.
- Tablets in which the motility control agent is ⁇ contained in a slowly dissolving core such as a core of stearic acid or castor oil are useful.
- Mixed release granule tablets comprising mixtures of the drug itself and the drug in separate particles coated with materials which dissolve at different rates such as dehydrogenated castor oil or fatty acids can also be employed.
- the active material can be bound to an ion exchange resin such as a sulfuric acid type cation exchange resin.
- the active agents of this invention are useful in treating the diseases to which this disclosure applies by inhibiting demyelination, thereby abating the progression of neurological disability.
- MS were treated orally using tablets containing 0.6 mg of colchicine three times per day.
- Treatment failure was defined as a decline in either the DSS or the Al/UEI by one point or the FSS by two points for a period of one month after beginning colchicine.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Méthode de traitement de maladies de démyélinisation telles que la sclérose en plaques par un traitement à base de colchicine ou colchicéine.Method of treatment of demyelination diseases such as multiple sclerosis by a treatment based on colchicine or colchiceine.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US79261085A | 1985-10-29 | 1985-10-29 | |
US792610 | 1997-01-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0245368A1 true EP0245368A1 (en) | 1987-11-19 |
EP0245368A4 EP0245368A4 (en) | 1988-01-25 |
Family
ID=25157487
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19860906690 Ceased EP0245368A4 (en) | 1985-10-29 | 1986-10-27 | Treatment of demyelinating diseases. |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0245368A4 (en) |
JP (1) | JPS63501154A (en) |
WO (1) | WO1987002583A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3626306A1 (en) * | 1986-08-02 | 1988-02-11 | Behringwerke Ag | USE OF 15-DEOXYSPERGUALIN AS A MEDICINAL PRODUCT |
EP4338740A1 (en) | 2022-09-13 | 2024-03-20 | Johannes Gutenberg-Universität Mainz | A transdermal patch for promoting or accelerating myelination and/or remyelination |
-
1986
- 1986-10-27 WO PCT/US1986/002298 patent/WO1987002583A1/en not_active Application Discontinuation
- 1986-10-27 EP EP19860906690 patent/EP0245368A4/en not_active Ceased
- 1986-10-27 JP JP50591786A patent/JPS63501154A/en active Pending
Non-Patent Citations (4)
Title |
---|
CHEMICAL ABSTRACTS, Vol. 106, No. 5, 2nd February 1987, page 30, Abstract No. 27521q, Columbus, Ohio, US; M.J. LYONS et al.: "Inhibition of acute experimental allergic encephalomyelitis in mice by colchicine", & J. Exp. Med. 1986, 164(5), 1803-8, Abstract. * |
CHEMICAL ABSTRACTS, Vol. 90, No. 23, 4th June 1979, page 436, Abstract No. 184235t, Columbus, Ohio, US; D.F. HORROBIN: "Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil", & Med. Hypotheses, 1979, 5(3), 365-78, Abstract. * |
CHEMICAL ABSTRACTS, Vol. 93, No. 26, 29th December 1980, page 382, Abstract No. 245390a, Columbus, Ohio, US; M. YOSHIDA: "Studies on entrapping of enzymes and drugs in matrixes by radiation-induced polymerization at low temperatures and their capabilities", & Nippon Genshiryoku Kenkyusho, (Rep.) Jaeri-M 1980, Jaeri-M-8766, Abstract. * |
See also references of WO8702583A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP0245368A4 (en) | 1988-01-25 |
JPS63501154A (en) | 1988-04-28 |
WO1987002583A1 (en) | 1987-05-07 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19870721 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 19880125 |
|
17Q | First examination report despatched |
Effective date: 19890824 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
|
18R | Application refused |
Effective date: 19910714 |