Composition for amelioration/prevention of adverse side effect in steroid therapy

A technology of composition and side effects, applied in the composition for inhibiting the expression of genes related to muscular atrophy, the new use of branched-chain amino acids, the combined use of composition and steroid drugs, to shorten the hospitalization period and treatment period, prevent recession, Effect of improving muscular atrophy

Inactive Publication Date: 2009-12-09
AJINOMOTO CO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, unknown branched-chain amino acids (for example, leucine, etc.) inhibit the expression of muscle atrophy genes (atrogin-1 and MuRF-1) whose expression increases due to muscle atrophy-inducing stimuli

Method used

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  • Composition for amelioration/prevention of adverse side effect in steroid therapy
  • Composition for amelioration/prevention of adverse side effect in steroid therapy
  • Composition for amelioration/prevention of adverse side effect in steroid therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0143] (Example 1) Muscular atrophy preventive effect of BCAA in dexamethasone-administered rats

[0144] Dexamethasone (600 μg / kg) was administered intraperitoneally to rats (SD; 10-11 weeks old) for 5 consecutive days. The isoleucine, leucine and valine (weight ratio 1:2:1.2) blend (BCAA) administration group was simultaneously orally administered with 0.75 g / kg of the above BCAA for 5 consecutive days. The vehicle group was sequentially administered orally with distilled water in the same manner.

[0145] On day 5, rats were necropsied and analyzed for functional assessment of muscle strength, blood glucose levels and plasma insulin levels using food intake, body weight profile, muscle weight, grip strength measurement devices.

[0146] As a control group, normal rats reared in pairs were used.

[0147] By comparison with the vehicle group, the BCAA administration group showed inhibition of body weight loss and reduction in food intake ( figure 1 ). The decrease in musc...

Embodiment 2

[0148] (Example 2) Muscle atrophy therapeutic effect of BCAA in rats administered with dexamethasone

[0149] Dexamethasone (600 μg / kg) was administered intraperitoneally to rats (SD; 10-11 weeks old) for 5 consecutive days to induce muscle atrophy. On the 6th and 7th days from the end of the dexamethasone administration, BCAA (0.75 g / kg) was orally administered, and the therapeutic effect on muscle atrophy was examined. The vehicle group was sequentially administered orally with distilled water in the same manner.

[0150] On days 6 and 7, rats were necropsied and analyzed for muscle weight. R1 and R2 are days 1 and 2, respectively, of the recovery period (recovery; R), and correspond to days 6 and 7 from the end of dexamethasone administration.

[0151] By comparison with the vehicle group, the BCAA administration group showed early recovery of muscle weight ( Figure 6 ).

Embodiment 3

[0152] (Example 3) Osteoporosis preventive effect of BCAA in dexamethasone-administered rats

[0153] Dexamethasone (600 μg / kg) was administered intraperitoneally to rats (SD; 10-11 weeks old) for 1.5 consecutive months. The isoleucine, leucine and valine (weight ratio 9:7:6) blend (BCAA) administration group was simultaneously orally administered with 0.75 g / kg of the above BCAA for 1.5 consecutive months. The vehicle group was sequentially administered orally with distilled water in the same manner.

[0154] At 1.5 months, rats were necropsied and analyzed for plasma ALP levels. It is known that plasma ALP shows a high value when bone metabolic turnover is high.

[0155] By comparison with the vehicle group, the BCAA administration group showed low plasma ALP values ​​( Figure 7 ).

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Abstract

Provided is a composition containing isoleucine, leucine and valine as active ingredients for improving or suppressing side effects associated with a steroid treatment and a composition for suppressing muscular atrophy-related gene. The composition improves or suppresses side effects in a steroid treatment such as muscular atrophy, muscular pain, arthritic pain, impaired glucose tolerance, decreased bone metabolism, impaired immunity, loss of appetite, body weight loss, fatigability and the like, and further suppresses muscular atrophy associated with various diseases. In addition, the composition suppresses muscular atrophy associated with promoted expression of muscular atrophy-related gene associated with glucocorticoid excess or renal failure pathology and the like. Therefore, the composition is effective form improving the QOL of patients.

Description

technical field [0001] The present invention relates to a composition for improving or suppressing side effects in steroid therapy, a composition for inhibiting muscle atrophy-related gene expression, and the combined use of the composition and steroid drugs. More specifically, the present invention relates to novel uses of branched chain amino acids. Background technique [0002] Symptomatic treatment of side effects in steroid therapy currently includes (1) infections: administration of antibacterial agents, (2) diabetes: administration of insulin and oral antidiabetics, (3) gastrointestinal symptoms: antacids and H2 blockade (4) osteoporosis: administration of vitamin D and calcium, (5) glaucoma: administration of ocular hypotensive agents, and (6) mental disorders and depressive states: administration of antipsychotics, etc. However, the only way to ameliorate or suppress myopathy, one of the serious side effects, is to reduce the dose of steroids. In addition, when mu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61P21/00A61P43/00A23L1/305A23L33/175
Inventor 西谷忍竹鼻健司
Owner AJINOMOTO CO INC
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