Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-02-08
2002-05-28
Dentz, Bernard (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06395747
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a novel use of a medicine for multiple sclerosis.
TECHNICAL BACKGROUND
Multiple sclerosis is a disease of the central nervous system, which is slowly progressive and is characterized by diffuse patches of demyelination in the brain and spinal cord, resulting in multiple and varied neurogic symptoms and signs, usually with repeated relapse and remission. The cause is unknown but an immunologic abnormality is suspected, with few clues presently indicating a specific mechanism (THE MERCK MANUAL, 16th EDITION, 1993 MERCK & CO.).
There are more multiple sclerosis cases in Europe and the United States than in Japan. In Japan, adrenocortical steroid, or vitamin B
12
is used for the therapy (Konnichi no Chiryo Shishin (TODAY'S THERAPY), 1995, Igaku Shoin K.K.). Myzoribine, which is an immunosuppressive agent, and interferon &bgr;1b are investigated as novel medicines (Asu no Shinyaku (New Medicine of Tomorrow), 1997, Technomic K.K.).
In Europe and the United States, where there are many patients with this disease, fundamental and clinical researches are being conducted actively. As the pharmacotherapy, interferon &bgr; is mainly investigated, and injectables of interferon &bgr; are supplied to clinical sites (SCRIP, No2223 p20 Apr. 15, 1997: SCRIP, No2227 p21 Apr. 29, 1997). In Europe and the United States, the interferon &bgr; is given, to patients with relapsing-remitting multiple sclerosis, subcutaneously in high doses every other day to decrease the frequency of neurological exacerbation (THE MERCK MANUAL, 16th EDITION, 1993, MERCK & CO.,INC). However, since the interferon &bgr; is expensive and should be administered for a long-term, such medical treatment becomes costly. So as to gain the higher medicinal compliance ratio, and less frequency of hospital attendance for higher quality of life of the patient, an orally administrable medicine has been desired.
Adrenocortical steroid can be administered orally for the therapy. However, the use of the adrenocortical steroid should be limited to remission of acute attack or the like since long-term of administration thereof may cause a side effect.
In recent years, pentoxifylline, and rolipram, which are respectively an inhibitor against an intracellular enzyme phosphodiesterase (hereinafter referred to as PDE), are reported to be possibly effective (Rott et al., Eur.J.Immunol., 23,p1745,1993; Nataf et al., Acta Neurol.Scand., 88,p97,1993; Genain et al., Proc.Natl.Acad.Sci., 92,3601,1995; Sommer et al., Nature Med., 1,p244,1995; Jung et al., J.Neuroimmunol., 68,p1, 1996; and Okuda et al., Immunopharmacol., 35,p141,1996). Oral administration of pentoxifylline was practically tested by multiple sclerosis patients, but the results of the evaluation for the medical effectiveness are not consistent (Rieckmann et al., J.Neurol., 242(Suppl.2),S112,1995; van Oosten et al., J.Neurol., 242(Suppl. 2),S-119,1995; Myers et al., Neurol., 45(Suppl.4), A419,1995); Rieckmann et al., J.Neuroimmunol., 64,p193,1996). Therefore, a medicine is demanded increasingly which is more effective and can be administered orally.
With the aforementioned background, a medicine for multiple sclerosis is demanded which is suitable for oral administration and is effective by a clinically applicable amount of dosage.
DISCLOSURE OF THE INVENTION
The inventor of the present invention, after comprehensive studies to find a useful compound as a medicine for multiple sclerosis, has found that ibudilast attains the above object, and has completed the present invention.
The present invention relates to a medicine for multiple sclerosis, comprising ibudilast represented by the chemical formula (1) below as the effective component:
The present invention relates also to a therapeutic treatment of multiple sclerosis by oral administration of a medicine containing ibudilast as an effective component.
The inventor of the present invention has found first the effect of ibudilast, for treatment of multiple sclerosis. The ibudilast is used widely in Japan as a medicine, and a large amount of safety information are available.
The ibudilast is a known compound represented by the above chemical formula (1) (Japanese Patent Publication Sho-52-29318 (1977), U.S. Pat. No. 3,850,941 (1974), etc.), developed by Kyorin Pharmaceutical Co., Ltd. as a medicine, and approved by Japanese Ministry of Health and Welfare for production and sale on January 1989. Since then, the ibudilast is widely used as a medicine for bronchial asthma and a cerebral circulation-improving agent. The known activities of the ibudilast includes potentiation of action of prostacycline (Onoue et al., Gen.Pharmacol., 23,p1093,1992) and resulting increase of regeional cerebral blood blow (Kudo et al., Folia Pharmacol. Jap.,85,p435,1995); leukotriene antagonism (Sato et al., Gen.Pharmacol., 17,p287, 1986; Ohashi et al., Int.Arch.Allergy.Immunol., 101,p.288,1993); suppression of leukotriene liberation (Tamura et al., Basic and Clinical Report, 20,p181,1986); inhibition of PDE (Souness et al., Brit.J.Pharmacol., 111,p1081,1994); and so forth. However, nothing has been known about the effectiveness thereof on the multiple sclerosis.
Ibudilast can be administered to humans in a pharmaceutically known formulation form and a dosing method, for example, in a form of powder, tablets, capsules, fine grains, granules, injection, solution, ointment, cataplasm, and so forth orally or parentally. An oral formulation is preferred in consideration of ease in use by a patient. The amount of the dosage of ibudilast depends on the age and body weight of the patient, conditions of the disease, and the method of the dosing. The amount of the oral dosage ranges preferably from 100 to 200 mg, more preferably from 10 to 60 mg in one dose, and dosing of two or three times per day is preferred.
REFERENCES:
patent: 5672622 (1997-09-01), Hedgepath et al.
Murashima et al, Inhibitory Effect of Ibudilast (KC-404) on Cyclic Nucleotide Phosphodiesterases, Jpn. Phamacol. Ther., vol. 26 No. 1. pp. 41-45 (1998).
Dentz Bernard
Reed Smith LLP
Sakoda Sauro
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