CN112957351B - Application of omega-3 polyunsaturated fatty acid and L-serine in preparation of synergist of breast cancer chemotherapeutic drug - Google Patents
Application of omega-3 polyunsaturated fatty acid and L-serine in preparation of synergist of breast cancer chemotherapeutic drug Download PDFInfo
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- CN112957351B CN112957351B CN202110284933.8A CN202110284933A CN112957351B CN 112957351 B CN112957351 B CN 112957351B CN 202110284933 A CN202110284933 A CN 202110284933A CN 112957351 B CN112957351 B CN 112957351B
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to application of omega-3 polyunsaturated fatty acid and L-serine in preparation of a synergist of a breast cancer treatment medicine. According to the invention, the chemotherapy medicaments are combined with omega-3 polyunsaturated fatty acid and L-serine to serve as the breast cancer treatment medicaments, so that the tolerance degree of a chemotherapy patient to high-intensity continuous chemotherapy can be effectively improved, the prognosis survival quality of the chemotherapy patient is effectively improved, and the nutrition loss caused by discomfort of the patient due to chemotherapy is avoided.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of omega-3 polyunsaturated fatty acid and L-serine in preparation of a synergist of a breast cancer chemotherapeutic drug.
Background
The incidence of malnutrition in malignant tumor patients is quite high, more than 50% of tumor patients have malnutrition with different degrees when treated according to statistics, the prognosis is obviously worse than that of patients with good nutrition, and the malnutrition is usually manifested as cachexia in the late stage. The reasons and mechanisms of malnutrition and cachexia of tumor patients are complex, and the reasons and the factors for anti-tumor treatment and systemic complex factors exist. Recent studies have demonstrated that metabolic alterations in tumor-bearing states are among the key factors.
Omega-3 unsaturated fatty acids, an important class of unsaturated fatty acids, are present in extremely abundant amounts in the body, are mainly distributed on cell membranes, particularly the pre-synaptic membranes of nerves, and have extremely important roles in maintaining the integrity of the brain's anatomical structure, biochemical and physiological functions. Mammals are unable to synthesize linoleic acid (linoleic acid, C18:2 n-6) and linolenic acid (alpha-linolenic acid, C18:3 n-3) using short carbon chains due to the lack of Δ -12 and Δ -15 desaturating enzymes necessary for the synthesis of long chain polyunsaturated fatty acids. Linoleic and linolenic acids in the human body are thus taken mainly by food as essential fatty acids to maintain normal physiological functions. Meanwhile, linoleic acid and linolenic acid are also important precursors for the synthesis of AA, DHA and EPA. These polyunsaturated fatty acids can be obtained not only directly from the food but also in the endoplasmic reticulum of the cells by means of chain elongation and desaturation using linoleic acid and/or linolenic acid. The liver, which is the main site of protein and fat metabolism in the body, is the main organ in the human body that synthesizes eicosa (AA and EPA) and docosana (DHA and DPA) polyunsaturated fatty acids using octadeca-polyunsaturated fatty acids from food sources, and long-chain polyunsaturated fatty acids, particularly DHA and AA, which are directly taken from food and synthesized by the liver, are mainly used to provide membrane phospholipids synthesized by body tissues.
L-serine is a potential glycine receptor agonist and is abundant in brain. In adult animals, activation of the glycine receptor induces Cl-Influx and neuronal hyperpolarization, thereby reducing neuronal excitability. The inventor's earlier research shows that L-serine can have neuroprotective effect on rats with focal cerebral ischemia reperfusion injury by activating glycine receptors in brain; activation of the glycine receptor may counteract the excitotoxic effects of glutamate by counteracting the depolarization of neurons during stroke, and the biochemical cascade that then leads to cell death. L-serine is a non-essential amino acid important in the central nervous system and is a precursor for synthesizing phosphatidylserine, sphingolipid, nucleotide and neurotransmitter D-serine; is also an important glial cell line-derived productTrophic factors play an important role in the survival of neurons and the growth of neurites. L-serine and its metabolites are not only required for cell proliferation, but also for specific functions in the central nervous system, required for brain development and many normal functions. Currently, L-serine has been used for the treatment of depression, schizophrenia, chronic fatigue syndrome, and for the prevention of bradykinesia, microcephaly, and the like.
Breast cancer is one of the most common malignant tumors of women, and during the proliferation process, tumor cells are often in stress microenvironments such as hypoxia, nutrition deficiency, oxidative stress and the like. How tumor cells adapt to such microenvironments to survive is an important issue of interest to researchers for many years. In a nutrient-deficient microenvironment, tumor cells promote proliferation and survival of the cells through metabolic changes and the like. Therefore, it is very important to fight the tumor cells to adapt to the nutrient-deficient microenvironment for survival and target treatment of breast cancer.
At present, malnutrition seriously affects prognosis and treatment tolerance of tumor patients, and reduces life quality of the tumor patients. With the widespread clinical application of nutrition therapy, a plurality of international nutrition guidelines describe the application of immunonutrients in tumor therapy, but most of the immunonutrients are scattered in the guidelines, and at present, no guideline is available for systematically teaching how the immunonutrients are applied to tumor prevention and treatment.
Disclosure of Invention
The chemotherapy medicament has the beneficial effects that the chemotherapy medicament has low immunity, the side effect caused by the chemotherapy medicament is mainly caused, and the omega-3 polyunsaturated fatty acid and the L-serine which are two nutrient substances beneficial to improving the immunity and the neural recovery of a patient are cooperatively given in the chemotherapy process, so that the immunity of the patient can be improved, the chemotherapy medicament is promoted to play a role, and the prognosis survival rate and the survival quality of a tumor patient are improved.
The invention provides an administration method of oral omega-3 polyunsaturated fatty acid and L-serine for breast cancer chemotherapy, aiming at clinical patients in chemotherapy, and improving the tolerance of the patients to the chemotherapy.
By adopting the omega-3 polyunsaturated fatty acid and the L-serine as the nutrition supply for the tumor chemotherapy, the effect of improving the prognosis survival quality of the chemotherapy patients by combining with the chemotherapy medicaments can be achieved.
Drawings
FIG. 1 is a photograph of tumors removed from the mice sacrificed 20 days after administration in example 1.
FIG. 2 is the body weight data of the mice of each experimental group in example 1.
Detailed Description
The invention is described in further detail below with reference to the figures and the specific examples, which should not be construed as limiting the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention. The experimental methods and reagents of the formulations not specified in the examples are in accordance with the conventional conditions in the art.
The invention provides a method for treating breast cancer by using omega-3 polyunsaturated fatty acid and L-serine in combination with a chemotherapeutic drug. The omega-3 polyunsaturated fatty acid and the L-serine are used as nutrient substances to ensure the nutrient supply of patients in the chemotherapy process so as to improve the resistance of the chemotherapy patients in the chemotherapy process and enhance the curative effect of chemotherapy.
Example 1
MCF-7/MDR cells were injected subcutaneously into the left dorsal side of 5-week-old female nude mice (4 mice per group) for the effect of nutrition supply during chemotherapy on the effect of chemotherapy. Divided into four groups, the first group: control group (i.e. no drug group); second group: a cisplatin administration group (mouse intraperitoneal cisplatin injection is used for administrating cisplatin injection at an optimal dose of 5mg/kg per injection and a scheme of administrating cisplatin 3 times every 7 days); third group: a omega-3 polyunsaturated fatty acid and L-serine compound group (omega-3 polyunsaturated fatty acid and L-serine compound oral intervention, namely performing compound food intervention rich in omega-3 polyunsaturated fatty acid and L-serine on mice every day from tumor inoculation, wherein each 24g of food contains 1000mg of fish oil and 100mg of L-serine); and a fourth group: cisplatin + omega-3 polyunsaturated fatty acid and L-serine compound group (i.e. receiving cisplatin administration and compound food administration at the same time).
As shown in figure 1, compared with the first group, the cisplatin alone chemotherapy group has a certain curative effect but has no obvious effect of the cisplatin combined with the omega-3 polyunsaturated fatty acid and L-serine compound oral intervention group.
As shown in figure 2, the weight of mice with omega-3 polyunsaturated fatty acid and L-serine in the chemotherapy process is obviously higher than that of other groups, and the cisplatin administration group shows obvious emaciation, which can indicate that the administration of omega-3 polyunsaturated fatty acid and L-serine is beneficial to enhancing immunity and improving absorption.
The above results demonstrate that administration of omega-3 polyunsaturated fatty acids and L-serine during breast cancer chemotherapy is beneficial to improve nutrient absorption and chemotherapy tolerance in the chemotherapeutic recipient for better quality of chemotherapy.
Claims (2)
1. The application of omega-3 polyunsaturated fatty acid and L-serine in preparing a synergist of a breast cancer chemotherapeutic medicament, wherein the breast cancer chemotherapeutic medicament is cisplatin.
2. A breast cancer chemotherapeutic drug, characterized by: consists of cisplatin, omega-3 polyunsaturated fatty acid and L-serine.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103355668A (en) * | 2008-09-19 | 2013-10-23 | 雀巢产品技术援助有限公司 | Nutritional support to prevent or moderate bone marrow paralysis or neutropenia during anti-cancer treatment |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103355668A (en) * | 2008-09-19 | 2013-10-23 | 雀巢产品技术援助有限公司 | Nutritional support to prevent or moderate bone marrow paralysis or neutropenia during anti-cancer treatment |
Non-Patent Citations (1)
| Title |
|---|
| ω-3 系列多不饱和脂肪酸生理功能及其机理;黄升谋;《襄樊学院学报》;20100531;第31卷(第5期);第16-19页 * |
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Effective date of registration: 20240413 Address after: Room 110-113, Building 2, No. 58 Chongchuan Road, Nantong City, Jiangsu Province, 226000 Patentee after: Mark Desen Nutrition Technology (Jiangsu) Co.,Ltd. Country or region after: China Address before: 226019 Jiangsu Province, Nantong City Chongchuan District sik Road No. 9 Patentee before: NANTONG University Country or region before: China |