Pharmaceutical composition for ameliorating, preventing, and treating anorexia and weight loss comprising bupleuri radix extract

Abstract

The present invention relates to a pharmaceutical composition for preventing, ameliorating, or treating anorexia and weight loss, comprising a Bupleuri Radix extract. Specifically, the present invention provides a pharmaceutical composition having effects in preventing, ameliorating, or treating anorexia and weight loss, wherein a Bupleuri Radix extract increases ghrilin, which is a hormone that stimulates appetite, and decreases TPH1(I), which is a serotonin synthase. In addition, a health functional food for preventing or ameliorating anorexia and weight loss, comprising a Bupleuri Radix extract, can be developed, and the extract can be effectively used for the treatment and the development of therapeutic agents for anorexia induced by chemotherapy in the future.

Description

Pharmaceutical composition for improving, preventing, and treating loss of appetite and weight loss containing Bupleurum extract

[0001] The present invention relates to a pharmaceutical composition for preventing, improving, or treating anorexia and weight loss comprising Bupleuri Radix extract, wherein the extract of Bupleuri Radix increases ghrilin, a hormone that promotes appetite, and decreases TPH1(I), a serotonin synthase, thereby providing a pharmaceutical composition effective in preventing, improving, or treating anorexia and weight loss.

[0002]

[0003] Loss of appetite refers to a state where the desire to eat is diminished or absent; in reality, this may involve a reduction in food intake compared to usual consumption or, in some cases, an inability to eat at all. Furthermore, loss of appetite can be a significant symptom of anorexia nervosa and may occur in conditions such as depression, cancer, or tuberculosis. While the causes of loss of appetite are diverse, treatment methods are known to vary depending on the underlying cause. Symptoms of loss of appetite can also occur as a side effect of chemotherapy drugs administered to cancer patients. This is because the administration of chemotherapy drugs to cancer patients is accompanied by severe loss of appetite due to the side effects of excessive drug toxicity. If this is dismissed as a mere symptom and treatment is neglected, weight loss, complications, and depression resulting from the loss of appetite will inevitably follow; therefore, it is essential to treat the condition simultaneously with chemotherapy or immediately upon the onset of loss of appetite caused by the drug. However, there is currently a significant shortage of agents available to prevent or treat loss of appetite resulting from the side effects of chemotherapy. However, currently used treatments (megestrol acetate, cyproheptadine) can cause side effects such as edema, and it has been reported that their effectiveness decreases with long-term use.

[0004] Meanwhile, Bupleurum belongs to the family Apiaceae / Umbelliferae and is a perennial herb found in mountains and fields throughout Korea; its flowering period is August to September and its fruiting period is September to October. Bupleurum is known by various names, including Buksiho, Sanchae, Sicho, Siho, Yeocho, Jacho, Jaho, Jihun, Chamsiho, Keunilsiho, Hyeopyeopsiho, Buksiho (a closely related species of the same genus), Wangsiho (a closely related species of the same genus), Seomssiho (a closely related species of the same genus), Gaesiho (a closely related species of the same genus), Daeyeopsiho (a closely related species of the same genus), Chamsiho (a closely related species of the same genus), and Hyeopyeopsiho (a closely related species of the same genus). The medicinal material of Bupleurum consists of single or branched roots, which are thick at the top and have a diameter of 5-15 mm. The lower part is slender and 10-15 cm in length, with the base of the stem remaining at the root cap. The outer surface is light brown to brown with deep wrinkles, is easily broken, and the broken surface is slightly fibrous. Bupleurum contains cycosaponins, sterol compounds, flavonoids, coumarins, and other essential oil components. Cycosaponin D extracted from Bupleurum exhibits inhibitory effects on liver damage, and has been confirmed to inhibit urinary protein excretion, reduce blood cholesterol, and have anticancer effects. Cycosaponin A has therapeutic effects on allergic asthma, such as suppressing asthma and inhibiting histamine-induced bronchoconstriction. Furthermore, Bupleurum has been shown to be effective against chronic gastric ulcers, and it is known to have excellent effects on hyperlipidemia by reducing cholesterol concentration in blood vessels and inhibiting blood aggregation caused by platelets.

[0005] However, substantial research on the effects of Bupleurum extract on improving anorexia and preventing or treating weight loss has not yet been reported.

[0006] Accordingly, the inventors investigated the effects of Bupleurum extract on preventing, improving, or treating loss of appetite and weight loss by increasing ghrilin, a hormone that promotes appetite, and decreasing TPH1(I), a serotonin synthase.

[0007]

[0008] The present invention was carried out with the support of the following project.

[0009] [Project ID] 2710077926

[0010] [Project No.] RS-2024-NR049559

[0011] [Ministry Name] Ministry of Science and ICT

[0012] [Name of Project Management (Specialized) Agency] National Research Foundation of Korea

[0013] [Research Project Name] Group Research Support (R&D)

[0014] [Research Project Title] Cancer Research Center for the Reinterpretation of Herbal Medicine

[0015] [Name of Project Performing Organization] (Seoul) Kyung Hee University Industry-Academic Cooperation Foundation

[0016] [Research Period] 2024.03.01 ~ 2027.02.28

[0017]

[0018] The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of anorexia.

[0019] In addition, the objective of the present invention is to provide a method for preparing a pharmaceutical composition for preventing or treating anorexia.

[0020] In addition, the objective of the present invention is to provide a health functional food for preventing or improving loss of appetite.

[0021] The problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned technical problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below.

[0022]

[0023] In order to solve the above problem, according to one aspect of the present invention, a pharmaceutical composition for preventing or treating loss of appetite is provided, characterized by comprising Bupleurum extract as an active ingredient.

[0024] According to one aspect of the present invention, a method for preparing a pharmaceutical composition for preventing or treating anorexia comprising a Bupleurum extract as an active ingredient is provided, comprising: 1) obtaining an extract by non-heating ultrasonic extraction of Bupleurum; 2) filtering the extract obtained in step 1) one to three times; 3) concentrating the filtrate obtained in step 2) under reduced pressure; and 4) freeze-drying the concentrate obtained in step 3).

[0025] According to another aspect of the present invention, a health functional food for preventing or improving loss of appetite is provided, characterized by comprising Bupleurum extract as an active ingredient.

[0026]

[0027] The Bupleurum extract of the present invention promotes appetite by regulating the secretion of ghrelin and serotonin, and exhibits efficacy in suppressing inflammatory responses in the body by reducing pro-inflammatory factors; furthermore, it demonstrates the effect of preventing and improving anorexia and weight loss induced by anticancer chemotherapy. In particular, the Bupleurum extract contributes to appetite enhancement and weight gain by increasing the synthesis of ghrelin in the gastrointestinal tract and decreasing the expression of TPH1, a serotonin synthesizing enzyme.

[0028] Therefore, the above-mentioned Bupleurum extract can be used in the future for the treatment of patients with anorexia and weight loss caused by various factors and for the development of new drugs. Furthermore, as a natural product, it has high safety, allowing for practical application without separate safety (toxicity) testing, and can be used as a composition for health functional foods.

[0029] The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the composition of the invention described in the description of the invention or the claims.

[0030]

[0031] Figure 1 shows the results of isolating and quantifying cycosaponins A and D from Bupleurum extract using HPLC.

[0032] Figure 2 is a diagram confirming the effect of Bupleurum extract (100 mg / kg) on ​​increasing feed intake and preventing weight loss in a mouse model with induced anorexia.

[0033] Figure 3 is a diagram confirming the inhibitory effect of Bupleurum extract on the expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by Cisplatin.

[0034] Figure 4 is a diagram confirming the effect of Bupleurum extract on the expression of ghrelin and serotonin synthesizing enzyme TPH1 in a Cisplatin-induced anorexia animal model.

[0035] Figure 5 is a diagram confirming the effects of Bupleurum extract (100 mg / kg) and cisplatin-induced anorexia and body weight loss in a mouse model of anorexia induced.

[0036] (A) Changes in total food intake

[0037] (B) Percentage change in food intake compared to previous intake

[0038] (C) Change in body weight

[0039] (D) Changes in food intake at each 24-hour interval

[0040]

[0041] The present invention will be described in detail below.

[0042] One aspect of the present invention provides a pharmaceutical composition for preventing or treating loss of appetite, characterized by comprising Bupleurum extract as an active ingredient.

[0043] In the present invention, the extract may be extracted by non-thermal ultrasonic extraction, but is not limited thereto.

[0044] In the present invention, the Bupleurum extract may comprise psychosaponin A represented by the following chemical formula 1 and psychosaponin D represented by the following chemical formula 2 as active ingredients.

[0045] [Chemical Formula 1]

[0046]

[0047] [Chemical Formula 2]

[0048]

[0049]

[0050] Bupleurum falcatum L. is a perennial herbaceous plant belonging to the Apiaceae family (Umbelliferae) that grows in mountainous areas throughout Korea. It is also known as Buksiho or Myeotminari. It thrives in well-drained environments in partial shade or full sun. The plant reaches a height of 40–70 cm; leaves emerging from the roots are 10–30 cm long, while those arising from the stem are pointed, measuring 4–10 cm in length and 0.5–1.5 cm in width. The flowers are yellow and borne at the tips of the main stem and branches; the central flower stalk is the longest, becoming shorter towards the ends. The fruit ripens around September or October and is flattened oval in shape.

[0051] Three major components of the olean saponin series—saikosaponin a, c, and d—along with various trace amounts of saikosaponin derivatives have been reported as the primary components of Bupleurum; these Bupleurum saponins a and d possess potent anti-inflammatory effects. The methanol extract of Bupleurum exhibits anti-nephritis effects by increasing the synthesis or release of corticosterone from the cortical cortex. In addition, it inhibits proteinuria and prevents skin damage caused by radiation.

[0052] As there are no reported studies on the prevention and improvement of loss of appetite and weight loss by Bupleurum chinense and its major components, psychosaponins A and D, the inventors confirmed the effects and mechanisms of action of Bupleurum chinense extract on preventing loss of appetite and weight loss through experiments.

[0053] In one embodiment, the extract of the present invention may be extracted with water, a C1 to C4 lower alcohol solvent, or a mixture of these solvents.

[0054] The term "extract" used in the present invention refers to a preparation obtained by squeezing a herbal medicine with a suitable extract and concentrating the extract by evaporating it. While it is commonly understood in the art as a crude extract, in a broader sense, it also includes fractions obtained by further fractionating the extract. That is, the Bupleurum extract includes not only that obtained using the extraction solvent described above, but also that obtained by applying an additional purification process thereto. For example, fractions obtained through various purification methods additionally performed, such as a fraction obtained by passing the extract through an ultrafiltration membrane having a specific molecular weight cut-off value, or separation by various chromatographs (designed for separation based on size, charge, hydrophobicity, or affinity), are also included in the extract. Furthermore, the extract may be, but is not limited to, an extract obtained by extraction treatment, a diluted or concentrated extract, a dried product obtained by drying the extract, or a modified or purified product thereof. The above Bupleurum extract can be prepared using general extraction, separation, and purification methods known in the ordinary art. The extraction methods may preferably include, but are not limited to, hot water extraction, hot water extraction, cold maceration extraction, reflux cooling extraction, or ultrasonic extraction.

[0055] In the present invention, the extract may be prepared by extracting with an extraction solvent or by adding a fractionation solvent to an extract prepared by extraction with an extraction solvent to fractionate it. The extraction solvent may be water, an organic solvent, or a mixture thereof, although it is not limited thereto. The organic solvent may be an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, a non-polar solvent such as hexane or dichloromethane, or a mixture thereof. Additionally, preferably, water, an alcohol having 1 to 4 carbon atoms, or a mixture thereof may be used.

[0056] In one embodiment, the Bupleurum extract may be included in an amount of 0.01 to 5 weight% with respect to the total weight of the composition of the present invention.

[0057] In one embodiment, the composition of the present invention can increase the expression of ghrelin and decrease the expression of inflammatory cytokines TNF-α, IL-1β, and IL-6.

[0058] In one embodiment, the composition of the present invention can reduce the expression of TPH1, a serotonin synthesizing enzyme.

[0059] In one embodiment, the composition of the present invention can improve one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss, fat loss, and hematopoietic toxicity.

[0060] In one embodiment, the anorexia may be anorexia induced by anticancer chemotherapy.

[0061] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier or diluent, and may be formulated according to conventional methods into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, as well as topical preparations, suppositories, and sterile injectable solutions. The pharmaceutically acceptable carrier includes 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, and mineral oil, etc. In addition, it includes diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Oral solid formulations include tablets, pills, powders, granules, capsules, etc., and these solid formulations may include at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., and may include lubricants such as magnesium stearate or talc. Oral liquid formulations include suspensions, liquid formulations, emulsions, syrups, etc., and may include diluents such as water or liquid paraffin, wetting agents, sweeteners, flavoring agents, preservatives, etc. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Witepsol, macrogol, Tween 61, cacao oil, laurin oil, glycerogelatin, etc., may be used as bases for suppositories.

[0062] The pharmaceutical composition of the present invention may be administered to mammals, such as livestock and humans, by various routes, for example, orally, desquamously, subcutaneously, intramuscularly, intravenously, intraperitoneally, intrarectally, intrauterine, dura mater or cerebrovascular injection, or by topical administration. Accordingly, the composition of the present invention may be formulated in various forms, such as tablets, capsules, aqueous solutions, or suspensions. For oral tablets, carriers such as lactose or corn starch and lubricants such as magnesium stearate may typically be added. For oral capsules, lactose and / or dried corn starch may be used as diluents. If an oral aqueous suspension is required, the active ingredient may be combined with an emulsifier and / or suspending agent. If necessary, specific sweeteners and / or flavoring agents may be added. For intramuscular, intraperitoneally, subcutaneously, and intravenously administration, a sterile solution of the active ingredient is typically prepared, and the pH of the solution must be appropriately adjusted and buffered. In the case of intravenous administration, the total concentration of the solute must be adjusted so as to impart isotonicity to the formulation. The composition according to the present invention may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier, such as saline solution with a pH of 7.4. The solution may be introduced into the intramuscular bloodstream of a patient by local injection.

[0063] The dosage of the active ingredient contained in the pharmaceutical composition of the present invention varies depending on the patient's condition and body weight, the severity of the disease, the form of the active ingredient, the route of administration, and the duration, and can be appropriately adjusted according to the patient. For example, the active ingredient may be administered at a dose of 0.0001 to 300 mg / kg per day, preferably 50 to 300 mg / kg, and the administration may be divided into one or two doses per day. In addition, the pharmaceutical composition of the present invention may contain the active ingredient at a weight percentage of 0.001 to 90% relative to the total weight of the composition.

[0064] In addition, according to one aspect of the present invention, a health functional food for preventing or improving loss of appetite is provided, characterized by comprising Bupleurum extract as an active ingredient.

[0065] The term "health functional food" above refers to a food manufactured and processed using raw materials or ingredients that have functional properties useful to the human body in accordance with the Health Functional Foods Act, and the term "functionality" means consuming for the purpose of obtaining useful effects for health purposes, such as regulating nutrients or physiological actions on the structure and function of the human body.

[0066] The health functional food of the present invention may include ordinary food additives, and unless otherwise specified, suitability as a "food additive" is determined according to the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the food additive code approved by the Ministry of Food and Drug Safety.

[0067] Examples of items listed in the above "Food Additives Codex" include chemically synthesized products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon dye, licorice extract, crystalline cellulose, sorghum dye, and guar gum; and mixed preparations such as L-sodium glutamate preparations, alkaline agents for noodle additives, preservative preparations, and tar dye preparations.

[0068] The health functional food of the present invention may contain a compound in an amount of 0.01 to 95%, preferably 1 to 80% by weight, relative to the total weight of the composition, for the purpose of preventing or improving anorexia and weight loss. Additionally, for the purpose of preventing or improving vascular diseases, it may be manufactured and processed in the form of tablets, capsules, powder, granules, liquid, pills, etc.

[0069] In one embodiment, the composition of the present invention may be a pharmaceutical composition for preventing or treating anorexia, comprising psychosaponin A represented by the following chemical formula 1 and psychosaponin D represented by the following chemical formula 2 as active ingredients.

[0070]

[0071] [Chemical Formula 1]

[0072]

[0073] [Chemical Formula 2]

[0074]

[0075] In addition, the method for preparing the pharmaceutical composition of the present invention comprises: 1) a step of obtaining an extract by non-heating ultrasonic extraction of Bupleurum; 2) a step of filtering the extract obtained in step 1) one to three times; 3) a step of concentrating the filtrate obtained in step 2) under reduced pressure; and 4) a step of freeze-drying the concentrate obtained in step 3).

[0076] Step 1) above may be extracted with a C1-C4 alcohol or a mixed solvent thereof, preferably with ethanol, but is not limited thereto.

[0077] In addition, the above step 1) may be performed for 1 to 3 hours, preferably 2 hours, but is not limited thereto.

[0078] In addition, the above 3) step may be performed at 50°C to 80°C, preferably at 60°C, but is not limited thereto.

[0079]

[0080] The present invention will be described in detail below by way of embodiments. However, the following embodiments are intended to specifically illustrate the present invention, and the scope of the present invention is not limited by the following embodiments.

[0081]

[0082] Example. Preparation of Bupleurum Extract

[0083] Preparation of Bupleurum Extract

[0084] Bupleurum purchased from N-Tap Hub Co., Ltd. of Chinese origin was used, and non-heating ultrasonic extraction was performed for 2 hours in 30% ethanol at a solvent ratio of 100 g / L. After filtering the extract using filter paper, a concentrate was obtained by vacuum concentration at approximately 60°C. The concentrate was freeze-dried to obtain an extract powder, and the Bupleurum extract obtained above was stored at -20°C and kept stable until it was used in the experiment.

[0085]

[0086] Experimental Example 1. Analysis of Psychosaponin A and D Content in Bupleurum Extract

[0087] HPLC analysis was performed to determine the content of psychosaponin A and psychosaponin D in the Bupleurum extract prepared in Example 1 above. Specifically, an analysis solution was prepared by ultrasonically extracting the Bupleurum extract solution (100 mg) prepared in Example 1 above with 50% methanol. An Agilent 1260 Infinity II HPLC was used, and the analysis was performed under the conditions of a YMC-Triart C18 column (250 x 4.6 mm, 5 μm), column temperature 35°C, detection wavelength 210 nm, injection volume 10 μL, and flow rate 1.0 mL / min. The mobile phase was analyzed using (A) ACN / (B) : 0.05% Formic acid in DDW under gradient conditions (A) 45% 0~7 min, 45~55% 7~15 min, 55~100% 15~17 min, 100% retention 3 min, and 100~45%.

[0088] Compound Standard Concentration Content (%) Average Content (%) Bupleurum Extract (30% EtOH) Saikosaponin A 20 1.2mg / 4ml (50% MeOH) 0.44 40.45 20 1.2mg / 8ml (50% MeOH) 0.45 9 Saikosaponin D 20 1.2mg / 4ml (50% MeOH) 0.11 70.10 20 1.2mg / 8ml (50% MeOH) 0.09 9

[0089] As a result of the HPLC analysis above, it was found that 100 mg of Bupleurum extract contained an average content of 0.45 for psychosaponin A and 0.1 for psychosaponin D.

[0090]

[0091] Experimental Example 2. Evaluation of the effects of Bupleurum extract in anorexia-induced rats

[0092] Conditions for administering Bupleurum extract

[0093] To evaluate the effects of Bupleurum extract, it was prepared at a concentration of 100 mg / kg, dissolved in 100 μL of distilled water, and administered to experimental subjects via oral administration (PO).

[0094] Appetite and weight loss effects

[0095] Feed intake and body weight change rates of Bupleurum extract were evaluated in a mouse model of anorexia induced. Bupleurum extract was administered orally at a concentration of 100 mg / kg, and the control group was set as not treated with either the chemotherapy agent (cisplatin) or Bupleurum extract.

[0096] As a result, looking at Figure 2, the group administered with Bupleurum extract showed a significant increase in feed intake and a preventive effect against weight loss compared to the group with anorexia induced by cisplatin administration, and the statistical significance was found to be at the level of p < 0.01, p < 0.001, and p < 0.0001.

[0097]

[0098] Experimental Example 3. Confirmation of the effect of Bupleurum extract on reducing genes inducing anorexia.

[0099] Bupleuri Radix was administered orally at a dose of 100 mg / kg. The control group received no treatment with either the anticancer agent or Bupleuri Radix extract, while the cisplatin group was administered the anticancer agent cisplatin and DW, the solvent for the Bupleuri Radix extract. The Bupleuri Radix extract administration group was defined as the group administered Bupleuri Radix extract along with cisplatin.

[0100] As a result, Bupleurum extract was found to significantly reduce the expression of TNF-α, IL-1β, and IL-6, pro-inflammatory cytokines known to induce anorexia (see Fig. 3). Conversely, the expression of ghrelin, an appetite-promoting hormone, increased (see Fig. 4 (A)), while TPH1, a serotonin synthase known to suppress appetite, significantly decreased (see Fig. 4 (B)). Meanwhile, there was no significant change in the expression of leptin, known as an appetite-suppressing hormone, between the two groups (see Fig. 4 (C)).

[0101]

[0102] Experimental Example 4. Effects of Psychosaponins A and D in Anorexia-Induced Rats

[0103] The effects of Bupleuri Radix and its components, cisplatin-induced anorexia and body weight loss were confirmed.

[0104] Psychosaponins A and D were purchased from ChemFaces and administered as a single intraperitoneal dose of 1 mg / kg dissolved in 15% MeOH, while the control group was set without treatment with either chemotherapy agent (cisplatin) or Bupleurum extract.

[0105] As a result, looking at Figure 5, the Bupleurum extract administration group and cycosaponins A and D showed a significant increase in feed intake and a preventive effect against weight loss compared to the group with anorexia induced by cisplatin administration.

[0106] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0107] The scope of the present invention is defined by the claims set forth below, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of the present invention.

[0108]

[0109] The composition for the prevention and treatment of loss of appetite and weight loss based on Bupleurum extract according to the present invention is highly safe as it consists of naturally derived ingredients and is effective in improving loss of appetite caused by anticancer treatment or chronic diseases; therefore, it can be industrially utilized as a pharmaceutical, health functional food, or nutritional supplement. In particular, since the mechanism of appetite promotion through the increase of ghrelin and the inhibition of TPH1 is clear, it has significant potential for commercialization in hospitals, nursing facilities, and the healthcare food industry. Accordingly, the industrial applicability of the present invention is clear in the pharmaceutical and functional food industries.

Claims

1. A pharmaceutical composition for preventing or treating loss of appetite, characterized by containing Bupleurum extract as an active ingredient.

2. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of anorexia, characterized in that the above extract is extracted by non-thermal ultrasonic extraction.

3. In Paragraph 1, A pharmaceutical composition characterized by the above extract containing psychosaponin A and psychosaponin D as active ingredients.

4. In Paragraph 1, A pharmaceutical composition characterized by the above extract being extracted with water, a C1 to C4 lower alcohol solvent, or a mixture thereof.

5. In Paragraph 1, A pharmaceutical composition characterized by containing the above Bupleurum extract in an amount of 0.01 to 5 weight% based on the total weight of the above composition.

6. In Paragraph 1, The above composition is a pharmaceutical composition characterized by increasing the expression of ghrelin and decreasing the expression of inflammatory cytokines TNF-α, IL-1β, and IL-6.

7. In Paragraph 1, The above composition is a pharmaceutical composition characterized by reducing the expression of TPH1, a serotonin synthesizing enzyme.

8. In Paragraph 1, The above composition is a pharmaceutical composition characterized by improving one or more symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss, fat loss, and hematopoietic toxicity.

9. In Paragraph 1, A pharmaceutical composition characterized in that the above-mentioned anorexia is anorexia induced by anticancer chemotherapy.

10. A health functional food for preventing or improving loss of appetite, characterized by containing Bupleurum extract as an active ingredient.

11. In Paragraph 10, A health functional food for preventing or improving loss of appetite, characterized in that the above extract is extracted by non-heating ultrasonic extraction.

12. In Paragraph 10, A health functional food characterized by the above Bupleurum extract containing psychosaponin A and psychosaponin D as active ingredients.

13. In Paragraph 10, The above health functional food is characterized by being selected from various drinks, meat, sausage, bread, candies, snacks, noodles, ice cream, dairy products, soup, isotonic drinks, beverages, alcoholic drinks, chewing gum, tea, and vitamin complexes.

14. A pharmaceutical composition for the prevention or treatment of anorexia comprising psychosaponin A and psychosaponin D as active ingredients. 15.1) A step of obtaining an extract by non-thermal ultrasonic extraction of Bupleurum; 2) A step of filtering the extract obtained in step 1) one to three times; 3) a step of concentrating the filtrate obtained in step 2) under reduced pressure; and 4) A step of freeze-drying the concentrate obtained in step 3) above; A method for preparing a pharmaceutical composition for preventing or treating anorexia comprising a Bupleurum extract containing as an active ingredient.

Images