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KR-102964048-B1 - PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER CACHEXIA

KR102964048B1KR 102964048 B1KR102964048 B1KR 102964048B1KR-102964048-B1

Abstract

The present invention provides a pharmaceutical composition for preventing or treating cancer cachexia, such as anorexia and weight loss, by administering a composition for blocking the Interleukin-4 (IL-4) signaling pathway to physically or chemically block the IL-4 neural signaling pathway and thereby suppressing cancer cachexia.

Inventors

  • 이찬희
  • 김새하
  • 장수연

Assignees

  • 한림대학교 산학협력단

Dates

Publication Date
20260511
Application Date
20240328

Claims (13)

  1. A composition for blocking the Interleukin-4 (IL-4) signaling pathway, comprising The above composition for blocking the Interleukin-4 (IL-4) signaling pathway blocks the hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nerve of POMC neurons within the hypothalamus, and A pharmaceutical composition for the prevention or treatment of cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway, which blocks neural signals of the hypothalamic-pituitary-adrenal axis (HPA axis), is mifepristone.
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  5. In paragraph 1, The above composition for blocking the Interleukin-4 (IL-4) signaling pathway blocks the Interleukin-4 receptor (IL-4 Receptor) located in hypothalamic microglia, and A pharmaceutical composition for the prevention or treatment of cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway that blocks the above-mentioned Interleukin-4 receptor (IL-4 Receptor) is Tamoxifen.
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  7. In paragraph 1, A pharmaceutical composition for the prevention or treatment of cancer cachexia, wherein the above pharmaceutical composition is administered by any one method selected from the group consisting of subcutaneous injection, intramuscular injection, subcutaneous injection, intraperitoneal injection, intraventricular administration, nasal administration, oral administration, transdermal administration, and oral administration.
  8. In paragraph 1, A pharmaceutical composition for the prevention or treatment of cancer cachexia, wherein the above pharmaceutical composition is contained in a syringe, a pen delivery device, an automatic injection delivery device, a glass vial, or a microinfuser.
  9. The method comprises the step of administering a pharmaceutical composition for the prevention or treatment of cancer cachexia, comprising a composition for blocking the Interleukin-4 (IL-4) signaling pathway, to an animal other than a human, and The above composition for blocking the Interleukin-4 (IL-4) signaling pathway blocks the hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nerve of POMC neurons within the hypothalamus, and A method for preventing or treating cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway, which blocks neural signals of the hypothalamic-pituitary-adrenal axis (HPA axis), is mifepristone.
  10. In Paragraph 9, A method for preventing or treating cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway is one of the compositions for blocking the hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nerve of POMC neurons, which are neuropeptide-secreting cells in the hypothalamus, or the composition for blocking the Interleukin-4 receptor (IL-4 Receptor) located in microglia of the hypothalamus.
  11. In Paragraph 9, A method for the prevention or treatment of cancer cachexia, wherein the above pharmaceutical composition is administered by any one method selected from the group consisting of subcutaneous injection, intramuscular injection, subcutaneous injection, intraperitoneal injection, intraventricular administration, nasal administration, oral administration, transdermal administration, and oral administration.
  12. A composition for blocking the IL-4 signaling system, comprising The above composition for blocking the Interleukin-4 (IL-4) signaling pathway blocks the hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nerve of POMC neurons within the hypothalamus, and A pharmaceutical preparation for the prevention or treatment of cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway, which blocks neural signals of the hypothalamic-pituitary-adrenal axis (HPA axis), is mifepristone.
  13. In Paragraph 12, A pharmaceutical preparation for the prevention or treatment of cancer cachexia, characterized in that the composition for blocking the Interleukin-4 (IL-4) signaling pathway is one of the compositions for blocking the hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nerve of POMC neurons, which are neuropeptide-secreting cells in the hypothalamus, or the composition for blocking the Interleukin-4 receptor (IL-4 Receptor) located in hypothalamic microglia.

Description

Pharmaceutical composition for preventing or treating cancer cachexia The present invention relates to a pharmaceutical composition for the prevention or treatment of cancer cachexia, and more specifically, to a pharmaceutical composition that inhibits cancer cachexia by physically or chemically blocking the neural signaling system of Interleukin-4 (IL-4). Cachexia is a syndrome commonly associated with chronic diseases such as cancer, tuberculosis, AIDS, and chronic obstructive pulmonary disease. It refers to a catabolic state of metabolism accompanied by persistent loss of appetite and weight loss, resulting in malnutrition, metabolic imbalance, and a decrease in muscle or fat. Unlike patients with other chronic diseases, cancer patients are characterized by the presence of not only cancer cachexia but also the side effects of various anticancer treatments used to treat cancer. Cancer cachexia occurs in 50–80% of patients with gastrointestinal and lung cancers, and the mortality rate due to cachexia reaches 20–30%. Cancer cachexia is characterized by weight loss resulting from muscle loss caused by increased inflammatory and catabolic responses triggered by various cytokines and metabolic changes. These changes lower the response rate to chemotherapy or radiation therapy, hinder the progression of effective anticancer treatment, and reduce the patient's quality of life. The mechanism of cancer cachexia development is known to involve changes in neuroendocrine activity, the secretion of various inflammatory cytokines (IL-1beta, IL-6, TNF-α, IL-4) and cancer-specific cachexia factors, and the resulting decrease in food intake and metabolic changes. Among these, inflammatory cytokines are proteins directly secreted by tumors or produced by the body's immune cells in response to tumors; they play a crucial role in immune regulation and contribute most significantly to the development of cachexia by causing loss of appetite and weight loss. Inflammatory cytokines are known to reduce appetite by inducing changes in taste or gastrointestinal function. Muscle loss is one of the most significant characteristics of cancer cachexia, and it is known to be caused by increased protein catabolism and decreased protein synthesis resulting from the overactivation of various cytokines. Cancer cachexia involves symptoms that include muscle loss (sarcopenia), so there is significant overlap between the two. While the majority of patients with cancer cachexia also have muscle loss (sarcopenia), not all patients exhibiting muscle loss display symptoms of cancer cachexia. Clinically speaking, muscle loss (sarcopenia) can be described as a prodromal symptom of cancer cachexia. Inflammatory cytokines acting on cancer cachexia affect insulin and testosterone, which regulate muscle metabolism, thereby causing abnormalities in muscle protein synthesis. Currently, progesterone preparations (megestrol acetate; megace) and steroids (dexamethasone, prednisone) are used to treat cancer cachexia; however, steroids do not provide sustained therapeutic effects and cause side effects such as fluid retention, insulin resistance, and adrenal insufficiency with long-term use, so they can only be prescribed for short periods. The progesterone preparation (megace) has been approved by the U.S. FDA for use in AIDS patients exhibiting anorexia or weight loss, and since it is currently approved in Korea for the treatment of cancer cachexia, it was used as the comparative drug of the present invention. However, it increases adipose tissue more than muscle and has side effects such as erectile dysfunction, uterine bleeding, thromboembolism, edema, hyperglycemia, and adrenal insufficiency. Patients exhibiting cancer cachexia show a poor response to anticancer treatment and experience severe side effects. Anticancer treatment methods for cancer patients broadly include surgical operation, chemotherapy, and radiation therapy. Surgery is a treatment method that removes the lesion (i.e., cancer); while early-stage cancer can be cured by surgery alone, mid-stage or later cancer cannot be treated by surgery alone. Chemotherapy, radiation therapy, or combination therapies all aim to eliminate targeted cancer cells by generating free radicals; however, due to their low specificity, they also damage normal cells that divide and proliferate rapidly, such as hematopoietic cells and immune cells. Therefore, it causes side effects such as vomiting, loss of appetite, stomatitis, diarrhea, constipation, fever, infection, leukopenia, thrombocytopenia, anemia, abdominal pain, nephrotoxicity, hepatotoxicity, cardiotoxicity, peripheral neurotoxicity, central neurotoxicity, muscle pain, bone pain, and bone marrow suppression. Cancer cachexia and muscle loss, which occur with high frequency in cancer patients, lower the response rate to anticancer treatment, hinder the progression of effective anticancer treatment, and reduce the patient's quality of life. Therefore, the d