Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-09-14
2000-10-17
Goldberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514372, 514374, 514401, A61K 31435, A61K 31425, A61K 3142, A61K 31415
Patent
active
06133278&
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
This invention relates to a pharmaceutical agent for the prevention and therapy of cachexia associated with chronic diseases such as malignant tumor, tuberculosis, diabetes, hemodyscrasia and endocrinopathy, among other diseases, which comprises a quinone compound as an active ingredient.
TECHNICAL FIELD
Cachexia involves progressive loss of body weight, anemia, edema and anorexia as cardinal symptoms, which is associated with malignant tumor, tuberculosis, diabetes, homodyscrasia, endocrinopathy, AIDS and so on "J. Parenteral and Enteral Nutrition, 12, 286-298, 1988" and "American Journal of Medicine, 85, 289-291, 1988".
Against cachexia, parenteral or enteral nutrition and endocrine therapy, for instance, have been attempted so far but no satisfactory therapeutic modality has been established as yet. Particularly where cachexia is caused by a malignant tumor, progression of cachexia diminishes the tolerance of patients for anticancer chemotherapy so that the treatment encounters a serious setback. On the other hand, palliative nutritional support for cachexia rather may exacerbate the malignant tumor to reduce the survival period of the patient. While cachexia is frequently induced by malignant tumors, administration of antitumor drugs may bring about antitumoral effects but it is the rule rather than exception that side effects of antitumor medication are superimposed to arrest a remission of cachexia.
There exists, under the circumstances, a need for a therapeutic drug that would ameliorate or inhibit progression of cachectic symptoms such as loss of body weight.
The present inventors previously constructed a cachexia model in mice by transplanting the colorectal cancer MAC16 of a mouse which had developed cachexia associated with the malignant tumor and showing clinical manifestations resembling those of a patient with cachexia in the abnormalities of lipid and protein metabolisms "British Journal of Cancer, 63, 337-342, 1991". In this model, chemotherapeutic agents in use clinically do not ameliorate cachexia and many of them do not show an antitumoral effect, either. Therefore, this model was found to be suitable for the evaluation of drugs for palliation of cachexia "Journal of National Cancer Institute, 81, 988-994, 1989". Meanwhile, for the purpose of solving the above problems, the inventors proceeded with an exploration for compounds antagonizing various symptoms of cachexia, such as loss of body weight, and as the result of intensive research, discovered that a certain class of quinone compounds has such activity.
BACKGROUND ART
EP-234729 describes that quinone compounds, exhibit two or more actions out of improvement of metabolism of higher unsaturated fatty acids (linoleic acid, .gamma.-linolenic acid, .alpha.-linolenic acid, arachidonic acid, di-homo-.gamma.-linolenic acid, eicosapentaenoic acid), particularly suppression of peroxy fatty acid production (antioxidant action) or suppression of production of 5-lipoxygenase metabolites (e.g., leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-peroxyeicosatetraenoic acid, lipoxins), thromboxane A.sub.2 synthetase inhibition, thromboxane A.sub.2 receptor antagonist, and active oxygen elimination, and that they are pharmaceutically useful as antithrombotic agents, antivasospasmodic agents, anti-asthmatic agents, anti-allergic agents, antipsoriatic agents, cardio-cerebro vascular circulation improving agents, nephritis remedies, active oxygen eliminators, anticancer agents and arachidonic acid cascade substance regulation improving agents. However, it does not mention cachexia.
DISCLOSURE OF INVENTION
With the aim of solving the above problems, the present inventors investigated in search of compounds that suppress various cachectic symptoms such as body weight loss, and found that quinone derivatives exhibit these effects.
The present invention relates to a prophylactic/therapeutic agent for a cachexia containing, as an active ingredient, a quinone derivative represented by the formula (I): ##STR3## wherein R.sup.1 and R.sup.2 i
REFERENCES:
patent: 4851413 (1989-07-01), Terao et al.
Ohkawa et al., The Journal of Medicinal Chemistry, vol. 34, No. 1, 1991, pp. 267-276.
Willette et al., Pharmacology Communications, vol. 1, No. 4, 1992, pp. 329-335.
Dinarello et al., Annals of the New York Academy of Sciences, vol. 587, 1990, pp. 332-338.
Cryan et al., Prostaglandins Leukotrienes and Essential Fatty Acids (1990) 39 (4) pp. 311-317.
Terao Shinji
Tisdale Michael John
Goldberg Jerome D.
Takeda Chemical Industries Ltd.
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