JPS63501154A - Treatment of demyelinating diseases - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Treatment of demyelinating diseases field of invention The present invention relates to demyelinating diseases, particularly Regarding the treatment of multiple sclerosis (MS) with colchicine or fluchceine. It is.

Background of the invention Demyelinating diseases of central or peripheral origin are mainly caused by fat and protein It is a disease that destroys miniphosphorus, which is a compound of substances. Minirin is a nerve fiber Communication along nerve fibers that are wrapped in many thin layers around them and act as insulators Accelerate the transmission of information. These scourges include, for example, MS, Guillain-Barré syndrome and This includes myositis. Among these, MS is also widespread due to its insulation properties. Book The invention will be described primarily in relation to MS.

MS is a disease of profound suffering and widespread displeasure, and its causes are completely unknown. Despite extensive research, it remains unclear. MS is associated with demyelination and Damage disseminated throughout the central nervous system resulting from subsequent scar formation. It consists of strips or platelets of miniphosphorus. The name ``multiple sclerosis'' In many diseases, there are many damaged areas filled with hardened (scarred) tissue. It states the fact that there is. New traditions and organizations develop over a long period of time. reached or the old expands. The result is a progressive degeneration of the nervous system that causes suffering. It causes progressive deterioration in affected individuals.

MS significantly affects the most productive age group <20-40 years. Victims only in the US There are nearly a million people. The outcome of this disease is primarily increased degeneration of neurological function. It's large. Most victims will be confined to wheelchairs or hospital beds after a thousand years. infection The rate ranges from 50/1oo and ooo in the United States to Canada, Northern England, parts of France, and Scandinavia. 200/1　oo　of Navya and Rocha, 0 over 000 for this disease. Since the cause of the condition is unknown, treatment has been empirical. Treatment is mainly It can be divided into anti-inflammatory drugs, immunosuppressive drugs, anti-infective drugs and biological response modifiers.

Additionally, numerous miscellaneous treatments have been attempted. No satisfactory treatment for MS has yet been shown. Not yet.

ACTH had some benefit in helping to calm severe attacks, but this disease It was not shown to limit overall progression. ACTH and cyclophospha Mitoto's combination therapy shows some promise of success in temporarily reversing the aggressive progression of MS. did. However, the research is very recent and no final conclusions have been reached. not present.

Copolymer, a synthetic polypeptide modeled after the basic protein miniphosphorus 1 showed some benefit, but it is difficult to properly evaluate these results because they are recent. I can't.

In 1982, the National Multiple Sclerosis Society (National Multiple Sclerosis Society) 5ociety) is a therapeutic claim for multiple sclerosis (The-r apeutic Claims in Multiple 5clerosis ) published a booklet entitled [International Standard Book Number (Internat) 1onalStandard Book Number) O-960809 8-0-5) o Among them, from food and drink management to anticoagulants, vasodilator nerve drugs, A wide variety of therapeutic drugs including immunosuppressive drugs and protease inhibitors More than 20 MS treatment methods are being discussed. The majority are ineffective and not recommended. It is characterized as having been poorly tested or not sufficiently tested.

methods of treating MS and related diseases to slow the progression of the disease, particularly For safe, reliable and effective treatment methods that delay demyelination before it becomes a tool in disease. There is a demand for If this treatment were to include the individual dosage units required each day during treatment, Sustained release compositions (5ustaine) that reduce the number of Especially if it can be accomplished with convenient.

Colchicine is (S)-N-(5,6,7,9-tetrahydro-9-oxabenzo 0 hepten-7-yl)acetamide. This is a human remedy, especially for gout. It has long been known as a depressant and treatment for familial Mediterranean fever.

It can be safely taken both orally and parenterally. inside the mammal body The activity in is well known and understood. Colchiceine is colchichi It is a 10-demethylated homolog of It has also been used for the same purpose. Ko Luchicine is a preferred therapeutic agent with known benefits. This is also a reasonable value, It is readily available at affordable prices and is highly effective in slowing the progression of MS. In addition, colchicine and fluchicine are now preferred agents for use in this invention. both treat demyelinating diseases like MS by slowing the progression of demyelination. It was discovered that it could be administered to humans. The therapeutic drug orally Although it is most convenient to administer the drug by administration, parenteral administration, including intravenous or intramuscular injection, Can be used.

Effective dosages to treat the disease are well known and understood by physicians. It will vary depending on the number of factors being used. These include, for example, the patient's age and Includes weight and disease status. Effective dosage is approximately 0.02 to 0 per day. ．． Of trui/kt body weight. Most conveniently, this The required dosage of contains 1.2 to 24 μ of active compound as the main active ingredient. Possible sustained release dosage units would be given in once-daily doses.

Another convenient dosage unit is 0.2 to 0.4119 active agents per stamped portion. A scored tablet containing the drug. like that Tablets allow physicians to investigate multiple dosage regimens and determine the optimal effective dosage for each individual patient. It is particularly useful because it allows titration of

Dosages appreciably lower than those suggested above will generally be ineffective. It was recognized that Dosages appreciably above these values are undesirable. Because of side effects, especially diarrhea, colchicine or flu Generally not recommended for patients using hiscein.

Oral and parenteral dosage units are prepared according to standard procedures and contain only Contains the selected active compound as one or the main active ingredient. what variety A variety of known inert excipients may also be used to prepare compositions useful in the practice of this invention. can be used. These allow therapeutic agents to dissolve or with the aid of known surfactants. Thus, as well as suspendable water or various miscible and immiscible aqueous compositions, e.g. Including dextrose, starch, talc, various types of clay, mineral oil, cottonseed oil or sesame oil Ru.

For oral and sublingual use, the active ingredient may be lactose or other palatable carbohydrates. It may be formulated in tablet form with water-soluble binders such as

For rectal administration, cocoa butter, petroleum, or other transcutaneous administration is recommended. Sustained release preparations that can be applied as patches are commonly used. se preparation) or gauze applied to the skin.

The method of dosing the active agent of the invention is preferably in the form of a sustained release dosage. be exposed. This is the most convenient option for the patient and provides constant, timed monitoring. This is because it avoids the need for protection or suspension of normal daily work. such tone A large number of compositions suitable for products are known and can be used effectively.

One convenient procedure is to use carnauba wax, cellulose esters and ethers, and fats. Various thicknesses such as fat, keratin, gluten or various natural or synthetic esters selected in time-degradable tablets or pellets coated with a known material of Prescribe a motility control agent That's true. In slowly dissolving cores such as those made of stearic acid or oil Tablets containing motility-controlling drugs are effective for this purpose. The drug itself and the dehydrogenated Individuals coated with substances that dissolve at different rates, such as mustard oil or fatty acids Mixed-release fine-grain tablets containing a mixture of drugs in particles can also be used. Wear. Alternatively, the active substance can be bound to an ion exchange resin, such as a sulfate-type cation exchange resin. It can also be combined.

The active agents of the present invention inhibit demyelination and thereby moderate the progression of neurological tools. It has been found that this method is effective in treating the diseases disclosed herein.

In one such trial, 16 MS patients with chronic progressive MS received He was treated using tablets containing 0.6 ml of colchicine orally.

All patients met the promulgated criteria for the clinical MS definition and had two neurological Chronic and progressive disease profile at the time of testing by an independent medical expert had.

The instruments used to measure the amount of disease are the Standard Neurological Examination (SNB) and the Functional Status Scale. (FSS), Tool Condition Scale (DSS), Gait Index (AI) and Upper Stiffness (E xtremity) index (UEI). Chronic progressive disease, required The definition of inclusion and removal of progress quantities and criteria shall be in accordance with standard, technically accepted guidelines. It was something like that. Patients are employed at Rockefeller University Hospital (RUH) obtained from the community and local practitioners. Patients are admitted to the RUH for up to two weeks and there CBC, ESR, SMA-6, SMA-12, UA, EKG, CXR, and ST Its medical and neurological research along with baseline laboratory studies involving tool guaiac oil A baseline study was conducted. Studies on lumbar pricking and immune function were also conducted.

Neurological evaluation during the course of treatment was performed independently by two neurologists. Notice After obtaining informed consent, patients begin treatment and are assessed at appropriate intervals to monitor their The condition was measured. Follow-up evaluations are based on background and material as described by the criteria above. It consists of physical examination, neurological examination, and laboratory research is CBCSBSR. , SMA-6, SMA-12, UA and the mysterious Stool Blood Ta. Treatment failure is defined as DSS or AI/UEI within 1 month after initiation of colchicine. It was defined as either one point decline in FSS or two points in FSS.

The results are shown in the table below.

FRCA/41/Male 3 6A 5 12JOFV42/'A 15 6B 6 10ALDE/34/Male 5 6A 4 9M C'46/Female 10 6B 6 9BAF'V42/Female 3 2 2 8 VIKU/32/Female 1 2 2 7 SUPF, /43/Female 9 3 2 7EPLI/61/Male 30 6A 4 6WAJ)y'35/Male 7 6B 6 5POFA/39/Female 20 5El 6 5JO8T/24/Female 2 2 2 5 MAJO/4s/Female 16 7 7 4RC) E [(155/Male 23 6A) 4 4JOCIV52/Male 25 6A 4 4HIHE156/Female 1 3 3 4 RIPR/47/Male 15 6A 5 4 *See proposal by Weiner et al. (N Eng, J, Med 19831308: 173-80) The integers in the columns under Discomfort and Gait Index are based on Wei n e r's experimental design. disease status at the start of treatment as measured by Among the patients tested, During the period indicated in the last column, persons whose disease has progressed beyond the initial condition shall be inspection report

Claims (5)

[Claims] 1. Colchicine or colchiceine in an effective amount to slow disease progression demyelination, consisting of administering to the patient a composition containing as the essential active ingredient Treating demyelinating diseases of central or peripheral origin to slow the progression of disease in patients suffering from the disease. How to treat. 2. 2. The method of claim 1, wherein the active ingredient is colchicine. 3. 3. The method according to claim 2, wherein the disease is multiple sclerosis. 4. Sustained release treatments containing colchicine or colchiceine as the main active ingredient Composition. 5. A composition according to claim 1, wherein the active ingredient is colchicine.