HMB compositions and uses thereof

a technology of compositions and hmb, applied in the field of hmb compositions and uses thereof, can solve the problems of weight loss, affecting overall prognosis, significant impact on morbidity and mortality, etc., and achieve the effect of reducing tumor growth ra

Inactive Publication Date: 2005-09-29
ABBOTT LAB INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0024] In another embodiment, the present invention provides a method for reducing tumor growth rate in a patient. The method comprises administering to the patient the above-describe

Problems solved by technology

Undesired weight loss, particularly lean mass loss is a relatively common occurance in critical illness, and has a significant impact on morbidity and mortality.
This is particularly true in cancer patients, where such mass losses can become tretment-limiting, and thus impact overall prognosis.
Weight loss is an independent risk factor for prognosis, and is often associated with increased oxygen consumption.
The majority of patients with cancer whose disease progresses to metastatic disease develop cachexia during their treatment program and the cachexia contributes to their deaths.
Although the relationship between pretreatment malnutrition (weight loss) and adverse outcome is established, no consistent relationship has been demonstrated between the development of cachexia and tumor size, disease stage, and type or duration of the malignancy.
For example, abnormalities in carbohydrate metabolism include increased rates of total glucose turnover, increased hepatic gluconeogenesis, glucose intolerance and elevated glucose levels.
Weight loss is common in patients with carcinomas of the lung and gastrointestinal tract, resulting in a massive loss of both body fat and muscl

Method used

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  • HMB compositions and uses thereof
  • HMB compositions and uses thereof
  • HMB compositions and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example i

Prevention of Weight Loss and Attenuation of Protein Degradation in Animals with Cancer Cachexia

[0104] This study evaluates the effect of HMB, in comparison with EPA or combination, on weight loss induced by the MAC16 tumor and the mechanisms involved. Weight loss induced by the MAC16 tumor is primarily induced by PIF.

[0105] Pure strain male NMRI mice (average weight 25 g) were obtained from our own inbred colony and were transplanted with fragments of the MAC16 tumor s.c. into the flank by means of a trochar, selecting from donor animals with established weight loss as described in Bibby, M. C. et al. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J. Natl. Cancer Inst., 78: 539-546, 1987. Transplanted animals were fed a rat and mouse breeding diet (Special Diet Services, Witham, United Kingdom) and water ad libitum, and weight loss was evident 10-12 days after tumor implantation. Animals just prior to the developmen...

example ii

Attenuation of Tumor Growth in Animals

[0113] The animal study described in Example I above also evaluated the effect of HMB on tumor growth rate in MAC16 cachectic tumor-bearing mice. The experiment was conducted as described in Example I.

[0114] A dose-response relationship of HMB alone on tumor growth rate in mice bearing the MAC16 tumor is shown in FIG. 2B. Differences from the control group are indicated as a, p<0.05; b, p<0.01 and c, p<0.005. Doses of HMB greater than 0.125 g / kg caused a significant reduction in tumor growth rate. Attenuation of tumor growth was not accompanied by an alteration in food and water intake.

example iii

Attenuation of Protein Degradation in Murine Myotubes

[0115] This study examines the effect of HMB on PIF-induced protein degradation and signalling pathways in murine myotubes to determine the mechanism of the attenuation of the increased expression of the ubiquitin-proteasome proteolytic pathway.

[0116] C2C12 myotubes were routinely passaged in DMEM supplemented with 10% FCS, glutamine and 1% penicillin-streptomycin under an atmosphere of 10% CO2 in air at 37□ C. Myotubes were formed by allowing confluent cultures to differentiate in DMEM containing 2% HS, with medium changes every 2 days.

[0117] PIF was purified from solid MAC16 tumors (Todorov, P. et al. Characterization of a cancer cachectic factor. Nature, 379: 739-742, 1996.) excised from mice with a weight loss of 20 to 25%. Tumors were homogenised in 10 mM Tris-HCl, pH 8.0, containing 0.5 mM phenylmethylsulfonyl fluoride, 0.5 mM EGTA and 1 mM dithiothreitol at a concentration of 5 ml / g tumor. Solid ammonium sulfate was adde...

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Abstract

The present invention relates to methods for the prevention and treatment of chronic inflammatory diseases, cancer, and involuntary weight loss. In the practice of the present invention patients are enterally administered HMB alone or alternatively in combination with eicosapentaenoic (20:5 ω-3), FOS, carnitine and mixtures thereof. HMB may be added to food products comprising a source of amino-nitrogen enriched with large neutral amino acids such as leucine, isoleucine, valine, tyrosine, threonine and phenylalanine and subtantially lacking in free amino acids.

Description

[0001] The present invention relates to methods for the prevention and treatment of chronic inflammatory diseases, cancer, and involuntary weight loss. In the practice of the present invention patients are enterally administered HMB alone or alternatively in combination with eicosapentaenoic (20:5 ω-3), FOS, carnitine and mixtures thereof. HMB may be added to food products comprising a source of amino-nitrogen enriched with large neutral amino acids such as leucine, isoleucine, valine, tyrosine, threonine and phenylalanine and subtantially lacking in free amino acids. BACKGROUND [0002] Undesired weight loss, particularly lean mass loss is a relatively common occurance in critical illness, and has a significant impact on morbidity and mortality. This is particularly true in cancer patients, where such mass losses can become tretment-limiting, and thus impact overall prognosis. [0003] Cachexia is a syndrome characterized by anorexia, weight loss, premature satiety, asthenia, loss of l...

Claims

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Application Information

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IPC IPC(8): A61K31/19A61K31/202A61K31/205A61K31/702A61P1/12A61P1/16A61P3/02A61P11/00A61P13/12A61P19/02A61P31/00A61P35/00
CPCA61K31/19A61K2300/00A61P1/00A61P1/04A61P1/12A61P1/16A61P11/00A61P13/12A61P17/02A61P19/02A61P21/00A61P25/18A61P29/00A61P3/00A61P3/02A61P3/04A61P3/12A61P31/00A61P31/18A61P35/00A61P37/00A61K31/205
Inventor BAXTER, JEFFREY H.MUKERJI, PRADIPVOSS, ANNE C.TISDALE, MICHAEL J.
Owner ABBOTT LAB INC
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