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Treatment or prevention of surgically induced cachexia and/or expression of myeloid-derived suppressor cells and proinflammatory cytokines

A technique for cachexia and surgery, applied in the field of the combination of inhibitory cells and pro-inflammatory cytokines, can solve the problems of inability to achieve complete recovery of skeletal muscle, impaired immune response, etc., to reduce paralytic ileus and reduce postoperative Effect of infection

Active Publication Date: 2020-10-02
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although radical cystoprostatectomy (RC) with urinary diversion is the gold standard for the treatment of invasive bladder cancer in men (ie, surgical removal of the bladder and reconstruction of the urethra with portions of the terminal ileum), the stress of surgery results in a catabolic state and impaired immune response, leading to precachexia and cachexia
On average, two weeks after surgery, RC surgery results in 5% weight loss, 7% loss of muscle mass, and complete recovery of skeletal muscle cannot be achieved even six months after surgery

Method used

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  • Treatment or prevention of surgically induced cachexia and/or expression of myeloid-derived suppressor cells and proinflammatory cytokines
  • Treatment or prevention of surgically induced cachexia and/or expression of myeloid-derived suppressor cells and proinflammatory cytokines
  • Treatment or prevention of surgically induced cachexia and/or expression of myeloid-derived suppressor cells and proinflammatory cytokines

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Experimental program
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Embodiment 1

[0099]57 patients were screened, 25 patients participated in the study, and 17 patients completed the study. Men with bladder cancer scheduled for RC were randomized to receive an immunonutritional drink (IMD) containing arginine, fish oil, and nucleotides (n=9) or an isocaloric placebo (ONS) for 5 days before and after surgery (n=9). 7). IMD provides 1,020kcal per day, 14.1g of arginine, 3.3g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and 1.2g of dietary nucleotides. ONS provides 1,080kcal, 1.8g of arginine, 0.0g of EPA and DHA and 0.0g of dietary nucleotides per day.

[0100] Blood was analyzed at baseline, surgery, 2 days post-surgery, 15 days post-surgery, and 30 days post-surgery ( figure 1 ). The baseline characteristics of each group are shown in figure 2 in the table.

[0101] The percentage of peripheral blood mononuclear cells (Lin-CD11b+CD33+) as MDSCs was determined by flow cytometry. pass Measurement of plasma arginine by liquid chrom...

Embodiment 2

[0110] To further compare the effect of IMD to control ONS, a second study was performed. Twenty-nine men scheduled to undergo primary bladder cancer RC were randomized using sequences generated by statisticians for either the IMD or ONS control groups. Block randomization using blocks of 10 will be used to assign participants according to a computer-generated randomization list with a predetermined ratio of 1:1. Statisticians were not involved in study conduct. Research coordinators can only access assignment lists through a password-protected file.

[0111] Wrap the carton with opaque tape and code it with numbers. Health care providers and data collectors were blinded to the intervention. The study was restricted to men to reduce the known variability in RC results across sex. Exclusion criteria were dysphagia, metabolism, ≥10% weight loss in the past six months, body mass index <18.5, viral infection, immunodeficiency, gout, or related food allergy. Instruct patients ...

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Abstract

The present invention discloses a specialized immunonutritional supplement that can be administered to surgical patients to reduce postoperative complications by limiting the expansion of myeloid-derived suppressor cells. The supplement comprises one or more of L-arginine, omega-3 fatty acids, vitamin A and dietary nucleotides, preferably all four of these compounds. The supplement is administered to the patient at least once a day for a period of time extending from a preoperative day three to seven days before the patient's bladder surgery to a postoperative day three to seven days after the bladder surgery. the day after tomorrow. The supplement may be administered to treat or prevent postoperative paralytic ileus in patients with bladder cancer; treat or prevent surgery-induced, inflammation-induced, or cancer-induced cachexia; reduce the expansion of suppressor cells caused by myeloid-derived suppressor cells in patients incidence of chronic infection; and / or reduced mRNA expression of pro-inflammatory cytokines in patients.

Description

[0001] priority statement [0002] This application claims the benefit of US Provisional Patent Application 62 / 116,155, filed February 13, 2015, which is hereby incorporated by reference in its entirety. Background technique [0003] The present disclosure generally relates to compositions and methods for treating or preventing surgery-induced cachexia and / or expressing myeloid-derived suppressor cells and pro-inflammatory cytokines. More specifically, the present disclosure relates to compositions comprising one or more of L-arginine, omega-3 fatty acids, vitamin A, and dietary nucleotides, and further to methods comprising administering such compositions to a patient . [0004] Cachexia is a severe body wasting disorder characterized by significant weight loss, anorexia, weakness and anemia. Cachexia is a common feature of diseases such as cancer, sepsis, chronic heart failure, rheumatoid arthritis and acquired immunodeficiency syndrome (AIDS). Furthermore, patients unde...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/07A61K31/198A61K31/202A61K31/7052A61P3/02A61P31/00A61P1/00A61P29/00A61P37/02
CPCA61K31/07A61K31/198A61K31/202A61K31/7052A61K2300/00A61K31/70A61K31/7088A61P1/00A61P1/04A61P29/00A61P3/00A61P3/02A61P31/00A61P31/04A61P35/00A61P37/02A61P37/04A61P43/00A23L33/12A23L33/13A23L33/14A23L33/30A23L33/175A23L33/155A23V2002/00A61K9/0053A61K9/0095
Inventor J·汉密尔顿-雷韦斯J·M·霍尔兹贝耶兰T·洋基
Owner SOC DES PROD NESTLE SA