Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1994-04-11
1995-10-31
Robinson, Douglas W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 288, A61K 3170
Patent
active
054629292
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a composition for curing proliferative skin diseases containing 4-carbamoyl-1-.beta.-D-ribofuranosyl-imidazolium-5-olate as an active ingredient.
PRIOR ARTS
4-carbamoyl-1-.beta.-D-ribofuranosyl-imidazolium-5-olate is a nucleic acid related compound which was found in a cultured broth of the strain Eupenicillium brefeldianum M-2199 belonging to genus Streptomyces and is given a generic name mizoribine. It is easily soluble in water and is a weakly acidic substance which is brown and decomposes with foaming at approximately 200.degree. C. Various production processes of mizoribine have been known. [J. Antibiotics, 27(10); 775 (1974), Chem. Pharm. Bull., 23; 245 (1975), Japanese Patent Unexamined Publication No. 48-56849, ibid., No. 51-1693, ibid., No. 50-121275, ibid., No. 50-121276 and others]
4-carbamoyl-1-.beta.-D-ribofuranosyl-imidazolium-5-olate (hereinafter sometimes designated as mizoribine) has an immunosuppressive activity and suppresses the rejection of the transplantation of an organ such as kidney. Mizoribine anhydrate crystal (bredinin. trade mark, tablet. Toyo Jozo Co.) has been applied as an immunosuppressant, which is prescribed for oral administration, with initial dose 2-3 mg/kg/day and maintenance dose 1-2mg/kg/day.
PROBLEMS TO BE SOLVED BY THE INVENTION
A proliferative skin disease, especially psoriasis is a common chronic, squamous dermatosis, marked by exacerbations and remissions. It is characterized clinically by the presence of rounded, circumscribed, erythemtous, dry, scaling patches of various sizes, covered by grayish white or silvery white, umbilicated and lamellar scales. Central clearing and coalescence of the lesions produce a wide variety of clinical configurations, including annular or circinate, discoid or nummular, figurate, and gyrate arrangements. The most distinctive histological findings in well-developed psoriasis are characterized by proliferative and hypertrophic epidermis, disappearance of granular layer and promotion of parakeratosis, and migrating the leukocytes into epidermis and horny layer from edematous and elongated derml papilla, and resulted to form Munro microabscesses.
Observing the total lesions of psoriasis beginning from primary puncrate lesion to well-developed sheet lesion, typical histopathological findings are observed in a central part at initial stage, thereafter, with developing an efflorescence, only found to move in peripheral region. Generally infiltration of mononuclear cells in an upper layer of dermis and nonspecific dermatitis which show proliferation and hypertrophy of epidermis with thick granular layer, are observed.
Epidermis of non-lesional skin of psoriasis patients responds easily proliferative reaction with stimulation as compared with that of the normal persons. Namely, the proliferative nature on epidermis is found, followed by nonspecific dermatitis caused by external or internal stimulation.
Therapeutics and treatment methods are disclosed, for example, in Japanese Patent Unexamined Publication No. 52-15827, ibid., No. 52-15828, ibid., No. 55-66511 and ibid., No. 53-47536. Among these, the former three publications relate to a medicine for external application and a medicine for topical injection, and the latter one discloses medicament for oral administration. These medicaments have been shown to have insufficient therapeutic efficacy and were not of practical use. Further no toxicological data was shown in the last one even though it is an oral medicament.
Cyclosporin which is known as an immunosuppressant is applied to a psoriasis patient (for example, refer to New England J. Med., 1989; 301: 555. Lancet, 1984; 11: 981-2, ibid., 1985; 1: 335. J. Am. Med. Assoc., 1986; 256: 3110-6, Brit. Med. J., 1986; 293:731-2 and Brit. J. Dermtol., 1986; 114: 615-20).
Inhibition of growth of epidermal keratinocyte cells is thought to be an effective treatment for psoriasis. Inhibitory action on growth of cultured human epidermal keratinocyte cells by cyclosporin has been repo
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Kamata et al., "Mechanism of the Immunosuppressive Action of Bredinin (Mizoribine)," Saishin Igaku, 41(11), 2509-2515 (1986); Chem. Abst., 106(13), p. 3, Abstr. No. 95429r (1987); see original publication with english abstract included.
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Gennaro et al. eds., Remington's Pharmaceutical Sciences, 18th Ed.,Mack Publishing Co., Easton, Pa., 1990, Chapter 61 (Immunoactive Drugs), see pp. 1142-1143.
Kamata et al., "Mechanism of the Immunosuppressive Action of Bredinin (Mizoribine)," Saishin Igaku, 41(11), 2509-2515 (1986); Chem. Abstr., 106(13), p. 3, Abstr. No. 95429r (1987); only Abstract supplied.
Kobayashi et al., "Therapeutic Effect of Mizorubine on Spontaneous Autoimmune Disorders in MRL/Mp-Ipr/Ipr Mice," Ensho, 12(2), 193-197 (1992); Chem. Abstr., 117(5), p. 46, Abstr. No. 40028f (1992); only Abstract supplied.
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Hori Kazuyoshi
Ishikawa Hiroaki
Kawashima Makoto
Morishita Masataka
Nagano Kazuhiro
Asahi Kasei Kogyo Kabushiki Kaisha
Crane L. Eric
Robinson Douglas W.
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