Method for the Prevention and Treatment of Cachexia and Anorexia

a cachexia and anorexia technology, applied in the field of cachexia and anorexia prevention and treatment, can solve the problems of increased total glucose turnover rate, no consistent relationship between the development of cachexia and tumor size, disease stage, type or duration of the malignancy, etc., and achieve the effect of reducing the amount of tryptophan and reducing oxidative damag

Inactive Publication Date: 2007-08-23
ABBRUZZESE BONNIE CHANDLER +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0029] In contrast to the prior art, the nutritional composition of the present invention is not restricted to correcting metabolism of just one nutrient class at a time, such as lipids or amino acids. Instead, a preferred nutritional multinutrient composition comprises a balanced formulation containing ω-3 fatty acids, antioxidants, branched-chain amino acids, and with or without a reduced level of tryptophan and 5-hydroxytryptophan. Such a composition can demonstrate strong inhibition of cachexia and anorexia associated with a variety of different cancers (disease states).
[0030] In yet another embodiment, the methods further optionally comprise administering the nutritional composition in combination with cancer chemotherapeutic agents, including but not limited to, 5-fluorouracil, mitomycin-C, adriamycin, chloroethyl nitrosoureas and methotrexate, to improve the transport of the drug into the target cancer cells and ultimately the efficacy of the anticancer agent.

Problems solved by technology

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.
Moreover, there have been problems reported with the use of high levels of medium-chain triglycerides and use of structured lipids has been suggested in some total parenteral nutrition formulas.
Moreover, these structured lipids do not provide the same benefits if administered enterally.
This method had serious drawbacks, including difficulty in swallowing, belching, and bad odor.
Thus, the prevention and / or treatment of cachexia and anorexia remain a frustrating problem.
Both animal and human studies suggest that nutritional support is largely ineffective in repleting lean body mass in the cancer-bearing host.
Randomized trials exploring the usefulness of total parenteral nutrition (TPN) support as an adjunct to cytotoxic antineoplastic therapy have demonstrated little improvement in treatment results.
This, along with a clear demonstration that TPN can stimulate tumor growth in animals suggests the routine use of TPN in cancer treatment is not justified.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example i

[0058] The specific list of materials for manufacturing the nutritional cancer product of this Example I is presented in Table 7. Of course, various changes in specific ingredients and quantities may be made without departing from the scope of the invention.

TABLE 7LIST OF MATERIALSINGREDIENTAMOUNTWATER31,605.21kgGUM ARABIC437.84kgULTRATRACE / TRACE MINERAL PREMIX14.50kgZINC SULFATE2969.89gmFERROUS SULFATE2856.50gmMANGANESE SULFATE784.60gmCUPRIC SULFATE423.11gmSODIUM MOLYBDATE21.39gmCHROMIUM CHLORIDE20.80gmSODIUM SELENITE8.11gmCITRIC ACID894.94gmSUCROSE (Carrier)6520.67gmPOTASSIUM CITRATE50.00kgSODIUM CITRATE95.00kgPOTASSIUM IODIDE9.00gmPOTASSIUM CHLORIDE91.00kgCORN SYRUP SOLIDS5630.96kgMALTODEXTRIN1407.52kgMAGNESIUM PHOSPHATE DIBASIC131.00kgCALCIUM PHOSPHATE TRIBASIC47.50kg(PREFERABLY MICRONIZED)CALCIUM CARBONATE122.50kgSUGAR (SUCROSE)852.77kgFRUCTOOLIGOSACCHARIDE509.96kgMEDIUM CHAIN TRIGLYCERIDES172.69kg(FRACTIONATED COCONUT OIL)CANOLA OIL99.13kgSOY OIL58.63kg57% VITAMIN A PALMITAT...

example ii

[0085] The objective of this experiment was to evaluate the organoleptic characteristics of nutritional composition of the invention fortified by the addition of branched-chain amino acids incorporated at two different levels. To measure organoleptic properties, three taste standards, described in Table 9, were prepared to rank the bitter and sour intensity of the test compositions containing branched-chain amino acids.

TABLE 9TASTE INTENSITY SCALEBasicConcentration*RepresentativeStandardTasteIntensityby WeightProducts1Sour10.05% Citric AcidMilk Chocolate,Coffee2Bitter10.05% CaffeineWhole Peanuts3Bitter20.10% CaffeineMilk ChocolateBeer

*Aqueous solutions

[0086] Two test compositions (designated “high” and “low”) were prepared by adding selected branched-chain amino acids (“BCAA”) to the liquid nutritional composition of Example I. A control composition of Example I that did not contain the supplemental branched-chain amino acids was also evaluated for flavor characteristics. The spe...

example iii

[0088] The effect of nutritional intervention with ω-3 fatty acids, branched-chain amino acids and antioxidants in the nutritional compositions of the invention, on prevention and treatment of cachexia can be monitored by any of the methods known to one skilled in the art, including but not limited to measuring: (i) food intake, body weight and anthropometric measurements; (ii) serum levels of lipids, fatty acids, amino acids and antioxidants; (iii) levels of serologic markers where appropriate, e.g., carcinoembryonic (CEA) antigens, serotonin, C-reactive protein, TNF and IL-1; (iv) changes in the morphology of tumors using techniques such as computed tomographic (CT) scan, ultrasonography, magnetic resonance imaging (MRI) and position emission tomography (PET).

[0089] Patients with hepatocellular carcinoma showing symptoms of cachexia are provided with the nutritional product of the invention with small, frequent feedings after surgical resection if the liver tumor is localized and...

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Abstract

The present invention relates to methods and nutritional compositions for the prevention and treatment of cachexia and anorexia. The methods of the invention comprise administering a composition comprising effective amounts of ω-3 fatty acids such as alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid or mixtures thereof; of branched-chain amino acids valine, leucine, isoleucine or mixtures thereof; with or without reduced levels of tryptophan and 5-hydroxytryptophan; and of antioxidant system selected from the group comprising beta-carotene, vitamin C, vitamin E, selenium, or mixtures thereof.

Description

[0001] This application is a continuation of U.S. patent application Ser. No. 10 / 784,451 filed on Feb. 23, 2004; which is a continuation of U.S. patent application Ser. No. 10 / 002,179 filed on Dec. 5, 2001 which is abandoned; which is a continuation of U.S. patent application Ser. No. 09 / 642,630 filed on Aug. 18, 2000 which is now U.S. Pat. No. 6,387,883; which is a continuation of U.S. patent application Ser. No. 09 / 479,550 filed Jan. 7, 2000, which is now U.S. Pat. No. 6,326,355; which is a divisional of U.S. patent application Ser. No. 08 / 842,454 filed Apr. 24, 1997, which is now U.S. Pat. No. 6,077,828; which is a continuation-in-part of U.S. patent application Ser. No. 08 / 635,179 filed Apr. 25, 1996 which is abandoned.[0002] The present invention relates to methods and nutritional compositions for the prevention and treatment of cancer cachexia and anorexia. In the practice of the present invention patients are enterally administered ω-3 fatty acids including, but not limited t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/00A61K31/70A61K31/202A61K45/00A23L1/30A23L1/304A23L1/305A23L33/00A61K31/015A61K31/195A61K31/20A61K31/355A61K31/375A61K33/04A61P3/00A61P3/02A61P7/00A61P35/00A61P37/04A61P43/00
CPCA23L1/296Y10S426/80A23L1/304A23L1/3051A23V2002/00A61K9/0029A61K31/202A61K31/70A61K47/12A61K47/183A23L1/3008Y10S426/801A23V2250/187A23V2250/1868A23V2250/708A23V2250/712A23V2250/1626A23V2250/5046A23V2250/211A23V2200/30A23V2200/308A23V2200/02A23L33/40A23L33/12A23L33/16A23L33/175A61P3/00A61P3/02A61P3/04A61P35/00A61P37/04A61P43/00A61P7/00
Inventor ABBRUZZESE, BONNIE CHANDLERMCCAMISH, MARK ANTHONYCOPE, FREDERICK OLIVERDEMICHELE, STEPHEN JOSEPH
Owner ABBRUZZESE BONNIE CHANDLER
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