A composition for improving or treating cancer cachexia containing calcium lactate as an active ingredient

Abstract

The present invention relates to a composition for improving or treating cachexia containing calcium lactate as an active ingredient, and a method for treating cancer cachexia in a subject, the method comprising the step of administering calcium lactate or a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof. The calcium lactate of the present invention acts as an Hif-1α inhibitor and exhibits the effect of suppressing body weight loss caused by cancer, so it can be used as a candidate substance for solving the problem of cancer cachexia, suggesting a synergistic effect between a medical nutritional product focusing on anorexia and malnutrition and an Hif-1α inhibitor.

Description

Technical Field

[0001] The present invention relates to a composition for improving or treating cancer cachexia containing calcium lactate as an active ingredient and / or a method for treating cancer cachexia in a subject.

Background Art

[0002] Cachexia is associated with various diseases such as heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and HIV / AIDS, and is characterized by muscle loss, weight loss, fatigue, and malnutrition. Among these, cancer cachexia is a complex metabolic syndrome accompanied by a malignant tumor, and is defined as a weight loss of 5% or more within 6 months after the occurrence of cancer due to muscle and fat loss. Cachexia can occur in a variety of medical conditions, but cancer cachexia is closely related to advanced cancer. Approximately 50% of all cancer patients, particularly approximately 80% of advanced cancer patients, are affected by cancer cachexia and suffer from a reduced quality of life and increased mortality due to muscle and fat loss. Cancer cachexia is characterized by weight loss due to significant loss of muscle and adipose tissue, and has characteristics different from muscle and fat loss through appetite suppression. Diagnostic criteria for cancer cachexia include a weight loss of 5% or more, high levels of inflammatory marker expression (IL6, CRP1, TNFr) at the serum level, reduced exercise ability, and loss of appetite.

[0003] Therapeutic agents for cancer cachexia include NSAIDs (non-steroidal anti-inflammatory drugs), β2-adrenergic agonists, corticosteroids, ghrelin, etc. However, the drugs most commonly used for the treatment of cancer cachexia that are currently on the market are COX-2 inhibitors and TNF-α inhibitors. COX-2 inhibitors are drugs that suppress COX-2, which is involved in the production of prostaglandins, an inflammatory substance that occurs in large amounts in cancer tissue, and reduce the loss of skeletal muscle. Celecoxib is commercially available as a COX-2 inhibitor. However, celecoxib has been reported to have side effects such as anemia, gastric ulcers, allergies, cardiac arrest, and stroke.

[0004] TNF-α inhibitors are drugs that reduce the expression of TNF-α, which is highly expressed in the serum of cancer cachexia patients, and kill cancer cells. Thalidomide is commercially available as a TNF-α inhibitor. However, these drugs have little effect as therapeutic agents for cancer cachexia and cause side effects such as depression, heart failure, dyspnea, vomiting, rash, hypertension, and the birth of deformed babies during pregnancy. Thus, most of the drugs that are currently under development or on the market have many side effects and lack a basis for their therapeutic effects. Therefore, the development of new mechanism-based therapeutic agents for cancer cachexia is an urgent situation.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention has been made to solve the above problems and meet the above needs, and an object of the present invention is to provide a composition for improving or treating novel cancer cachexia.

[0007] Another object of the present invention is to provide a method for improving or treating novel cancer cachexia.

Means for Solving the Problems

[0008] To achieve the above object, the present invention provides a composition for improving or treating cachexia containing calcium lactate as an active ingredient.

[0009] In one embodiment of the present invention, the cachexia is preferably, but not limited to, induced by cancer.

[0010] In another embodiment of the present invention, the composition preferably, but not limited to, improves one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, muscle loss, fat loss, and hematotoxicity.

[0011] Further, the present invention provides a method for treating cancer cachexia in a subject, the method comprising the step of administering calcium lactate or a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof.

[0012] Further, the present invention provides the use of calcium lactate in the manufacture of a medicament for preventing or treating cancer cachexia in a subject.

[0013] Hereinafter, the results of the following examples of the present invention will be described together with the drawings.

[0014] FIG. 1 is a diagram showing that a Hif-1α inhibitor suppresses cancer-induced body weight loss, and the important involvement of Hif-1α in cancer cachexia suggests a synergistic effect between medical nutrition products focused on anorexia and malnutrition and Hif-1α inhibitors.

[0015] TME anoxia / hypoxia has a considerable impact on various aspects of cancer cachexia, deteriorating the patient's condition, and it can be seen that the Hif-1α inhibitor and medical nutritional products of the present invention have a common goal of solving the cachexia problem in a complementary approach.

[0016] Figures 2 to 4 are diagrams showing that calcium lactate of the present invention does not affect normal cells and degrades tumor Hif-1α protein in a hypoxic state. The upper panel of Figure 2 is to confirm the effect of calcium lactate treatment on the survival of normal colon fibroblasts. When treated with calcium lactate, there is no toxicity to normal cells, indicating that there is no change in survival. The lower panel of Figure 2 is to confirm the effect of calcium lactate treatment on the survival of colorectal cancer cells. When treated with calcium lactate, the death of cancer cells can be observed due to the anti-cancer effect.

[0017] The upper panel of Figure 3 is to confirm the change in the expression of Hif-1α protein after calcium lactate treatment in colorectal cancer cells under normoxia or hypoxia conditions. Under normoxia conditions, the expression of Hif-1α cannot be observed, and it can be seen that the expression of Hif-1α expressed under hypoxia conditions is decreased by calcium lactate treatment. The lower panel of Figure 3 shows the PK analysis in muscle and tumor tissues after calcium lactate treatment. In tumor tissues, the concentration of lactic acid increases at 2 hours after the administration of calcium lactate, while there is no change in muscle tissues.

[0018] Figure 4 is to confirm the change in Hif-1α expression by calcium lactate treatment in HCT-116 (colorectal cancer), AsPC-1 (pancreatic cancer), MDA-MB-231 (breast cancer), and H1975 (lung cancer) cell lines, and it can be confirmed that the expression of Hif-1α decreases after calcium lactate treatment in all cell lines.

[0019] Figures 5 to 6 are diagrams showing the results of the Phase 2 clinical trial. As can be seen from Figure 5, there is a negative correlation between body weight change and tumor size change. Among a total of 16 metastatic colorectal cancer patients who did not respond to standard therapy, the body weights of 8 patients were maintained or increased, and the increase range was 0.0% to 10.6%. The body weights of 6 patients decreased, and the decrease range of body weight was 0.8% to 6.7%. Cachexia was observed in 2 patients. The median increase in tumor size was observed to be 17% in the 8 patients with weight loss including cachexia and 9.5% in the 8 patients with weight maintained or increased.

[0020] As can be seen from Figure 6, there is a positive correlation between body weight change and overall survival. The median overall survival was observed to be 4.15 months in the 8 patients with weight loss including cachexia and 8 months in the 8 patients with weight maintained or increased.

[0021] Among a total of 16 patients, cancer cachexia progressed in only 2 patients, suggesting that calcium lactate can prevent patients from cachexia with an efficacy of 87.5%. The drug efficacy of calcium lactate for tumor growth arrest is 68.8%, showing the highest potential at the metastatic stage of the anti-tumor effect. No dose limiting toxicity (DLT) was observed in the Phase 2 clinical trial.

[0022] Pharmaceutical composition for preventing or treating cachexia The present invention provides a pharmaceutical composition for preventing or treating cachexia comprising calcium lactate or a pharmaceutically acceptable salt thereof.

[0023] As used herein, the term "cachexia" refers to the severe systemic debilitation symptoms seen in the terminal stages of diseases such as cancer, tuberculosis, diabetes, and Acquired immunodeficiency syndrome (AIDS), and frequently appears in patients with digestive system cancers such as gastric cancer, esophageal cancer, pancreatic cancer, and colorectal cancer, as well as in patients with lung cancer. It also presents symptoms such as decreased appetite, weight and physical strength loss due to muscle and fat loss, anemia, fatigue, and indigestion. In particular, it indicates a state where normal food intake is difficult due to decreased appetite, or a state where weight loss occurs even with normal food intake. When cachexia occurs, patients show a low response to anti-cancer chemotherapy and radiotherapy, resulting in a decline in the quality of life, a shortening of life expectancy, and inducing death due to weight loss in 10% to 20% of all cancer patients.

[0024] In the pharmaceutical composition according to the present invention, the cachexia may be induced by cancer. In one embodiment of the present invention, the cachexia induced by cancer is expressed as "cancer cachexia".

[0025] Cancer as defined in the present application may include colorectal cancer, leukemia, lymphoma, myeloma, myelodysplastic syndrome, breast cancer, head and neck cancer, esophageal cancer, gastric cancer, colon cancer, rectal cancer, anal cancer, hepatocellular carcinoma, cholangiocarcinoma, gallbladder cancer, pancreatic cancer, lung cancer (non-small cell lung cancer, small cell lung cancer), thymic cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, ovarian cancer, cervical cancer, sarcoma, gastrointestinal stromal tumor (GIST, DisT), cancer of unknown primary origin, mesothelioma, melanoma, neuroendocrine tumor, skin cancer, blood cancer, etc.

[0026] The pharmaceutical composition according to the present invention may be one that improves one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, muscle loss, fat loss, and hematotoxicity, and preferably may be one that improves one or more symptoms selected from the group consisting of weight loss, muscle loss, and fat loss.

[0027] In the pharmaceutical composition according to the present invention, the expression "pharmaceutically acceptable salt" means any organic or inorganic addition salt of calcium lactate that has a concentration with a relatively non-toxic and harmless effective action on the patient and whose side effects due to this salt do not reduce the advantageous efficacy of calcium lactate. For these salts, inorganic acids and organic acids can be used as the free acid. As the inorganic acids, hydrochloric acid, bromic acid, nitric acid, sulfuric acid, perchloric acid, phosphoric acid, etc. can be used. As the organic acids, citric acid, acetic acid, lactic acid, myrenic acid, fumaric acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, tartaric acid, galacturonic acid, embonic acid, glutamic acid, aspartic acid, oxalic acid, (D) or (L) malic acid, tansulfonic acid, ethanesulfonic acid, 4-toluenesulfonic acid, salicylic acid, benzoic acid, malonic acid, etc. can be used. Also, these salts include alkali metal salts (such as sodium salts, potassium salts, etc.) and alkaline earth metal salts (such as calcium salts, magnesium salts, etc.). For example, the acid addition salts can include acetate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camsylate, citrate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, maleate, marilate, malonate, mesylate, methyl sulfate, naphthylate, 2-naphthylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, saccharate, stearate, succinate, tartrate, tosylate, trifluoroacetate, aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, zinc salts, etc.

[0028] The acid addition salts according to the present invention are produced by a normal method, for example, dissolving calcium lactate in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc., adding an organic acid or an inorganic acid, filtering and drying the produced precipitate, or by distilling off the solvent and the excess acid under reduced pressure and then drying, or by crystallization under an organic solvent.

[0029] Also, pharmaceutically acceptable metal salts can be made using a base. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, as the metal salt, it is appropriate to produce sodium, potassium or calcium salts in the pharmaceutical industry. Also, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0030] Furthermore, the present invention may include not only the calcium lactate and its pharmaceutically acceptable salts, but also possible solvates, hydrates, isomers, optical isomers, etc. that can be produced therefrom.

[0031] The pharmaceutical composition according to the present invention can be formulated for oral administration, intramuscular administration, intravenous administration, intraperitoneal administration, subcutaneous administration, intradermal administration, or topical administration.

[0032] The calcium lactate of the present invention or its pharmaceutically acceptable salt can be administered in various oral and parenteral dosage forms during clinical administration. When formulating, it is produced using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc.

[0033] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, etc. Such solid preparations are prepared by mixing at least one or more excipients, such as starch, calcium carbonate, sucrose, lactose or gelatin, with one or more calcium lactates of the present invention or pharmaceutically acceptable salts thereof. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions or syrups. In addition to water and liquid paraffin, which are frequently used simple diluents, various excipients, such as wetting agents, sweeteners, flavoring agents, preservatives, etc., may be included.

[0034] Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspension solvents, emulsions, freeze-dried preparations, suppositories, etc. As non-aqueous solvents and suspension solvents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used. As the base of suppositories, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerol, gelatin, etc. may be used.

[0035] The pharmaceutical composition may further contain a carrier, an excipient or a diluent. The carrier, excipient or diluent can include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0036] In addition, the pharmaceutical composition may further contain a known active ingredient having preventive or therapeutic activity against cancer cachexia. The effective dosage of calcium lactate or a pharmaceutically acceptable salt thereof of the present invention for the human body may vary depending on the patient's age, weight, gender, dosage form, health status, and degree of the disease, but generally ranges from about 0.001 to 100 mg / kg / day, preferably 0.01 to 35 mg / kg / day. Based on an adult patient weighing 70 kg, it is generally 0.07 to 7000 mg / day, preferably 0.7 to 2500 mg / day, and can also be administered once or divided into several times a day at regular time intervals according to the judgment of a doctor or pharmacist.

[0037] Health functional food and health food composition for improving cachexia In addition, the present invention provides a health functional food composition for improving cachexia containing calcium lactate or a food-acceptable salt thereof.

[0038] The term "health functional food" used in the present invention refers to a food manufactured and processed in the form of tablets, capsules, pills, liquids, powders, granules, etc. using raw materials and ingredients having useful functionality for the human body. Here, "functionality" means adjusting nutrients for the structure and function of the human body or obtaining useful effects for health applications such as physiological effects. The health functional food of the present invention can be manufactured by methods commonly used in the normal technical field, and during the manufacturing, normal raw materials and ingredients in the normal technical field can be added for manufacturing. Also, the dosage form of the health functional food can be manufactured without limitation as long as it is a dosage form recognized as a health functional food. The health functional food composition of the present invention can be manufactured in various dosage forms, but different from general pharmaceuticals, since it uses food as a raw material, it has the advantage of not causing side effects that may occur during long-term administration of drugs, and is excellent in portability. Therefore, the health functional food of the present invention can be ingested as an adjuvant for enhancing the effects of a cancer cachexia therapeutic agent or an anticancer agent.

[0039] Furthermore, the present invention provides a health functional food composition for improving cachexia containing calcium lactate or a food-acceptable salt thereof.

[0040] The above-mentioned health functional food composition or health food composition according to the present invention can add the calcium lactate or its food-acceptable salt to health functional foods or health foods such as foods and beverages for the purpose of preventing or improving cancer cachexia.

[0041] There is no particular limitation on the type of the food. Examples of foods to which the calcium lactate or its food-acceptable salt according to the present invention can be added include drink agents, meats, sausages, breads, biscuits, mochi, chocolates, candies, snacks, confectioneries, pizzas, ramen, other noodles, gums, dairy products including ice creams, various soups, drinking water, alcoholic beverages and vitamin complex agents, dairy products and processed dairy products, etc., including all health foods and health functional foods in the ordinary sense.

[0042] The above-mentioned health functional foods and health food compositions according to the present invention can be added directly to foods or used together with other foods or food ingredients, and can be appropriately used by ordinary methods. The mixing amount of the calcium lactate or its food-acceptable salt according to the present invention can be appropriately determined according to its use purpose (for prevention or improvement). Generally, the amount of the calcium lactate or its food-acceptable salt in health foods and health functional foods can be added in an amount of 0.1 part by weight to 90 parts by weight of the total food weight. However, in the case of long-term intake for the purpose of maintaining health or regulating health, the amount may be below the above range, and there is no problem in terms of safety, so the active ingredient can also be used in an amount above the above range.

[0043] The health food and health functional food composition of the present invention, except for containing calcium lactate according to the present invention or a food - pharmaceutically acceptable salt thereof as an essential component in the indicated ratio, has no special restrictions on other components, and can contain various flavoring agents or natural carbohydrates, etc. as additional components together with ordinary beverages. Examples of the above - mentioned natural carbohydrates are monosaccharides such as glucose, fructose, etc.; disaccharides such as maltose, sucrose, etc.; and polysaccharides such as dextrin, cyclodextrin, etc., which are ordinary sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (such as rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the above - mentioned natural carbohydrates is generally about 1 g to 20 g, preferably about 5 g to 12 g per 100 g of the health functional food composition of the present invention.

[0044] In addition to the above, the health food and health functional food composition containing calcium lactate according to the present invention or a food - pharmaceutically acceptable salt thereof can contain various nutritional agents, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers (such as cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the health food and health functional food composition of the present invention can contain pulp for the production of natural fruit juice, fruit juice beverages and vegetable beverages.

[0045] The above - mentioned components can be used independently or in combination. The ratio of such additives is not limited thereto, but is generally selected in the range of about 0.1 part by weight to 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the active substance of the present invention.

[0046] Adjuvant composition for cancer treatment Furthermore, the present invention provides an anti-cancer adjuvant composition comprising the pharmaceutical composition for preventing or treating cachexia.

[0047] The term "anti-cancer adjuvant" used in the present invention can be used to increase the anti-cancer therapeutic effect and suppress or improve the side effects of anti-cancer agents, and can be administered to patients in combination with anti-cancer agents.

[0048] The anti-cancer adjuvant composition of the present invention exhibits the effect of suppressing or improving symptoms of cachexia such as muscle loss, weight loss, fat loss, hematotoxicity, and decreased appetite induced by cancer, and may increase the anti-cancer effect of anti-cancer agents.

[0049] Existing anti-cancer agents defined in the present application may include cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustine, vincristine, procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, cisplatin, epirubicin, cisplatin, capecitabine, oxaliplatin, and immuno-oncology agents, etc.

[0050] In addition to containing calcium lactate or a pharmaceutically acceptable salt thereof as an active ingredient, the anti-cancer adjuvant composition may further contain one or more active ingredients exhibiting the same or similar functions. The anti-cancer adjuvant can be administered orally or parenterally during clinical administration. When administered parenterally, it can be administered by intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine epidural injection, intracerebrovascular injection, or intrathoracic injection, and can be used in the form of general pharmaceutical preparations.

[0051] The anti-cancer adjuvant can be used alone or in combination with each of the methods using surgery, radiotherapy, hormone therapy, chemotherapy, and biological response modifiers. The daily dosage of the anti-cancer adjuvant is about 0.0001 mg / kg to 1000 mg / kg, preferably 1 mg / kg to 100 mg / kg, and it is preferably administered once or several times a day. However, the range varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of the disease. The anti-cancer adjuvant of the present invention can be administered in various parenteral dosage forms during actual clinical administration. When formulating, it is prepared using diluents or excipients such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspension solvents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate can be used. As the base of suppositories, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerogelatin, etc. can be used.

Advantages of the Invention

[0052] As can be understood through the present invention, calcium lactate of the present invention acts as an Hif-1α inhibitor and exhibits the effect of suppressing weight loss caused by cancer. Therefore, it can be used as a candidate substance for solving the problem of cancer cachexia, suggesting a synergistic effect between medical nutritional products focusing on anorexia and malnutrition and Hif-1α inhibitors.

Brief Description of the Drawings

[0053]

Figure 1

Figures 2-4

Figures 5-6

Modes for Carrying Out the Invention

[0054] Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following examples.

[0055] Example 1: Cytotoxicity assay 5x10 of CCD-18Co, a normal colon fibroblast cell line, or HCT-116, a colorectal cancer cell line, was cultured in a 96-well plate 3 in a 37°C and 5% CO2 incubator and observed under a microscope after 48 hours.

[0056] Example 2: Western blot Tumor tissues or HCT-116 and AsPC-1 (pancreatic cancer cells), MDA-MB-231 (breast cancer cells), and H1975 (lung cancer cells) were cultured in 24-well plates under hypoxic (1% O2) conditions. After culturing, proteins were extracted from the group without calcium lactate treatment and the group treated with calcium lactate. After electrophoresis, the proteins were transferred to polyvinylidene difluoride membranes. Next, the Hif-1α antibody was diluted in TBST and applied to the proteins on the membrane. After washing with TBST and treating with the secondary antibody, the band results were confirmed through X-ray film or Gel doc equipment.

[0057] Example 3: Tissue pharmacokinetics (PK) Balb / c nude mice were secured, and 1x10 6 of HCT-116 was transplanted subcutaneously to grow tumors. After that, 20 mg / kg of calcium lactate was injected subcutaneously (S.C.). Muscle tissues and tumor tissues were obtained before dosing and at 30 minutes, 1 hour, 2 hours, and 4 hours after dosing. For each obtained tissue, a lactate analysis kit was used to analyze the change in lactate concentration over time.

[0058] Example 4: Efficacy of calcium lactate against cancer cachexia in clinical practice The clinical study was a phase 2 clinical trial targeting metastatic colorectal cancer patients who were refractory to standard therapy.

[0059] Twenty-two patients were enrolled, and 16 completed the clinical trial (see Table 1).

[0060] The change in body weight was calculated as the change from the value measured at screening to the value one month after calcium lactate treatment. The change in tumor size of the target lesion was measured based on RECIST 1.1. The administration method was subcutaneous injection, and the administration dose was 100 mg / day. After subcutaneous IP administration once a day for 5 days, the second day was a rest period, and a 4-week treatment cycle was composed of one cycle.

[0061] Tumor evaluation was performed every two cycles compared to the baseline.

[0062] The clinical outputs were that the primary output was the disease control rate, and the secondary outputs were the overall survival period, progression-free survival period, and safety.

[0063] The body weight was measured at the first month after the start of administration and is shown as the increase or decrease in body weight before and after administration. The tumor response was measured by CT scan at the second month after the start of administration and is shown as the increase or decrease in tumor size before and after administration. SD indicates that tumor growth has stopped, and PD indicates that the tumor has increased by 20% or more.

[0064]

Table 1

[0065] Among the total of 16 people, 11 are patients with stable disease, so the disease control rate is 68.75%.

[0066]

Table 2

[0067] As can be seen from the table, among the total 16 people who completed the clinic, 8 had weight gain after the calcium lactate administration clinic, 6 had weight loss (not corresponding to cachexia), and 2 corresponded to cachexia.

Claims

1. A composition for improving or treating cachexia, containing calcium lactate as an active ingredient.

2. The composition according to claim 1, wherein the cachexia is induced by cancer.

3. The composition according to claim 1, wherein the composition improves one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, muscle loss, fat loss, and hematotoxicity.

4. A method for treating cancer cachexia in a subject, the method comprising administering calcium lactate or a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof.

5. Use of calcium lactate in the manufacture of a medicament for preventing or treating cancer cachexia in a subject.

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