KR101710081B1

KR101710081B1 - Composition comprising extract of rhizome of Curcuma phaeocaulis and uses thereof

Info

Publication number: KR101710081B1
Application number: KR1020140143619A
Authority: KR
Inventors: 노문철; 오현미; 이우송; 이철; 정경숙; 이승웅; 이소영; 권형준
Original assignee: 한국생명공학연구원
Priority date: 2014-10-22
Filing date: 2014-10-22
Publication date: 2017-02-24
Also published as: WO2016064214A1; KR20160047329A

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of viral or bacterial infectious diseases, a quasi-drug composition, a virus, or a bacterium, which increases the activity of TLR4 and TLR7 / 8 and is capable of inducing the production of interferon beta, A food or feed additive for preventing or improving infectious diseases. The extract or its fraction provided by the present invention induces the activation of TLR4 and TLR7 / 8 and the production of interferon beta, thereby enhancing the TLR-mediated immune activity, thereby preventing, treating or ameliorating a virus or bacterial infection Therefore, the composition can be manufactured into various forms such as a pharmaceutical composition for preventing or treating viral or bacterial infectious diseases, a quasi-drug composition, a health functional food composition for preventing or improving viral or bacterial infectious diseases, a feed or a feed additive.

Description

Composition comprising extract of Curcuma phaeocaulis and uses thereof < RTI ID = 0.0 >

The present invention relates to compositions comprising extracts of the extract and to uses thereof, and more particularly the present invention relates to a composition comprising extracts of the extract or fractions thereof capable of increasing the activity of TLR4 and TLR7 / 8 and inducing the production of interferon beta A pharmaceutical composition for preventing or treating viral or bacterial infectious diseases, a quasi-drug composition, a health functional food composition for preventing or improving viral or bacterial infectious diseases, a feed or feed additive.

An immune response is a series of reactions caused by activated immune cells against adventitious and endogenous substances (antigens). When a microorganism including a bacterium, a virus, or a foreign body of a living body enters the living body, the host cell secretes a factor such as cytokine which causes the inflammation reaction to overcome the infection and induces an inflammatory reaction. When these microorganisms and living organisms are recognized by the immune cells, the immune cells are activated, and in the activated immune cells, many factors that cause the inflammation reaction are secreted to induce an inflammatory reaction (Chen GY, Nat. Rev Immunol., 10 (12): 826-837, 2010).

The development of molecular biology and genetic engineering has revealed molecular targets in cells related to this. Especially in the early stage of nonspecific congenital immune reaction of external antigens, a gene that recognizes a specific part of a pathogen has been identified, A new molecular mechanism is being analyzed. Recently, Toll-like receptors (TLRs) have been recognized as pathogen-recognizing pathogens in the early stages of inflammation by lipopolysaccharide (LPS), peptidoglycan and nucleic acid constructs (ds RNA, single strand RNA, GpG DNA, etc.), TLRs have been actively studied (Brown, et al, J. Dent. Res., 2010, Epub ahead of print: Palusinska-Szysz M., et al ., Folia Microbiol. (Praha), 2010, 55 (5), 508-14).

TLR is a type I transmembrane signaling molecule that is mainly expressed in cells responsible for the innate immune system. In these cells, TLRs recognize pathogen-associated molecular patterns (PAMPs) or microorganism-associated molecular patterns (MAMPs) through the extracellular domain and consequently induce inflammatory cell activation in innate immune cells. Since TLRs have been identified, efforts have been made to find PAMPs that bind to TLRs, and up to now, one or more ligands have been identified, with the exception of TLR10, TLR12, and TLR13 (Kawai T. et al., Ann. NY Acad. , 1143, 1-20). TLRs are different but share a signaling mechanism (Liew F. Y., et al., Nat. Rev. Immunol., 2005, 5 (6), 446-458).

A common feature in signaling by TLRs is the activation of NF- [kappa] B through the Toll (Toll / interleukin-1 receptor-like domain) domain. TLR-mediated signal transduction interacts with MyD88 with the TIR domain to form a complex. The TIR domain located at the C-terminal of MyD88 forms a complex with TLR and the Death domain located at the N-terminal is complexed with IRAK (IL-1R associated kinase) -1 or IRAK-2, which is a phosphorylating enzyme (Ser / Thr kinase) . IRAK-1 activates NIK (NF-κB-inducing kinase) through interaction with TRAF6 (tumor necrosis factor receptor-associated factor 6), NIK activates phosphorylation of IKK (IκB kinase) Re-phosphorylates IκB (inhibitory κB), resulting in activation of NF-κB. Activated NF-κB migrates to the nucleus and acts as a transcription factor and induces expression of cytokine and cell junction molecule-related genes (Brown J., et al., J. Dent. Res., 2010, Epub ahead of print: Palusinska-Szysz M., et al., Folia Microbiol. (Praha), 2010, 55 (5), 508-14).

TLR-7 is known to recognize single-stranded RNA (ssRNA) and poly-I (polyinosinic acid), an ssRNA analogue. In other words, TLR-7 recognizes ssRNA and then reacts with adapter protein MyD88 to activate transcription factors NFkB and AP-1 to produce inflammatory cytokines. As another mechanism, the TRIF-dependent mechanism induces the production of type I interferon by continuously delivering signals to TRIF, ANK-binding kinase 1 (TBK1), TRAF3 and the transcription factor IRF3. TLR-3 is known to recognize double-stranded RNA (dsRNA) and polyinosinic-polycytidylic acid (dsRNA), both of which occur during the growth of RNA viruses. In other words, after recognizing the dsRNA as an ectodomain of the leucine-rich repeat motif of TLR-3, it reacts with the adapter protein TRIF to activate the transcription factors IRF3 and NFκB, Type IFN and inflammatory cytokines such as IL-6 and IL-12 (Alexopoulou L., et al, Nature, 2001, 413, 732-738).

Under these circumstances, the inventors of the present invention have made extensive efforts to develop a formulation that can enhance the immune activity more safely and effectively. As a result, it has been found that when the extract or fraction thereof, which is a natural product, is used, the activity of LR4 and TLR7 / And can induce the production of interferon beta, and can be used for the prevention or treatment of viral or bacterial infectious diseases in a manner that enhances TLR-mediated immunological activity. Thus, the present invention has been completed.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating a virus or bacterial infectious disease comprising an extract or its fraction as an active ingredient.

Another object of the present invention is to provide a quasi-drug composition for preventing or treating a virus or bacterial infectious disease comprising an extract or its fraction as an active ingredient.

It is still another object of the present invention to provide a health functional food composition for preventing or ameliorating a virus or bacterial infectious disease comprising an extract or its fraction as an active ingredient.

It is still another object of the present invention to provide a feed or feed additive for preventing or ameliorating a virus or bacterial infectious disease comprising an extract or a fraction thereof as an active ingredient.

As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating viral or bacterial infectious diseases comprising an extract or its fraction as an active ingredient.

The term "rhizome of Curcuma " phaeocaulis "is a medicinal plant belonging to the genus Ginger, which is widely referred to as 朮朮朮, 莪 출 朮, 莪莪戌, 廣朮, and 廣戌It is used as a medicinal herb in folk medicine and oriental medicine, and it has the effect of eliminating hemorrhoids, eliminating umbilical blood, helping the circulation of 气, .

The term "extract of an extract of the present invention" means an extract obtained by extracting the extract. For the purpose of the present invention, the extract of the extract is preferably a mixture of water, (Methanol, ethanol, butanol, etc.) or a mixed solvent thereof, more preferably, hot water as a solvent, but the present invention is not limited thereto, and the resultant product may be a diluted solution of an extract, , A dried product obtained by drying the extract, or any of these adjusted products or purified products.

The term "fraction " of the present invention means a product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. In the present invention, preferably, the extract obtained by fractionation of the above extract by various methods such as a solvent fractionation method, an ultrafiltration fractionation method, and a chromatography fractionation method.

According to one embodiment of the present invention, the effect of the above extract on the activation of TRL4 or TRL7 / 8 was examined by treating the above extract with various concentrations to obtain a hot-water extract of the above extract (Example 1) The extract was found to activate the activity of TRL4 or TRL7 / 8 in a concentration-dependent manner, and particularly when it was treated at a concentration of 60 μg / ml, the activity of TRL4 or TRL7 / 8 could be increased by 200% or more Table 1, Fig. 1, Table 2 and Fig. 2). In addition, it was confirmed that it exhibited an effect of actively inducing the production of interferon beta (Table 3 and Fig. 3).

Therefore, it has been confirmed that the extract has an effect of increasing the activity of TLR4 and TLR7 / 8 by more than 200% and actively inducing the production of interferon beta. Therefore, the extract of the present invention enhances the TLR- Or bacterial infectious disease.

The extract of the present invention has an effect of preventing or treating a virus or a bacterial infection in a manner that increases the activity of TLR4 and TLR7 / 8 and induces the production of interferon beta. The preventive or therapeutic effect of the virus or bacterial infection may be induced by enhancing the TLR mediated immune activity. Diseases which can be prevented, alleviated or treated due to the prevention or treatment of the virus or bacterial infectious disease of the extract, But is preferably an infectious disease of a host caused by an infection of an external antigen such as a bacterium, a fungus, or a virus. More preferably, the virus may be a rotavirus, a Colorado fever fever virus, a reovirus, a human immunodeficiency virus, a B Chronic pelvic inflammatory disease, endometritis, rhinitis, encephalitis, meningitis, AIDS, chronic hepatitis, and chronic hepatitis caused by infection of various viruses or bacteria such as hepatitis C virus, Osteosarcoma, viral hepatitis, genital herpes, herpes zoster, herpetic keratitis, herpes simplex, Large cell pneumonia, viral coryza, a variety of diseases such as chronic hepatitis C, severe acute respiratory syndrome may be indicative of disease symptoms, either alone, or in combination it induced. It has already been known from the results of previous studies that the disease can be caused by a virus or a bacterial infection and can be prevented, improved, improved and treated through TLR mediated immunity enhancement (NATURE IMMUNOLOGY, 5 (10): 975-979, 2004; NATURE, 6: 823-835, 2006; J. Invest. Dermatol., 125: 1-8, 2005; Cell, 124 (4): 783-801)

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the manufacture of pharmaceutical compositions. Specifically, the pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method . In the present invention, the carrier, excipient and diluent which may be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The content of the extract or its fraction contained in the pharmaceutical composition of the present invention is not particularly limited, but may be in the range of 0.0001 to 50% by weight, more preferably 0.01 to 20% by weight, based on the total weight of the final composition .

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount " of the present invention means a therapeutic or prophylactic treatment of a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention And the effective dose level refers to the level of the disease to be treated, the severity of the disease, the activity of the drug, the age, body weight, health, sex, sensitivity of the patient to the drug, Duration, duration of administration, factors involved in combination with or contemporaneously with the composition of the present invention, and other factors well known in the medical arts. The pharmaceutical composition of the present invention may be administered alone or in combination with a known immunotherapeutic agent. It is important to take into account all of the above factors and administer an amount that will achieve the maximum effect in the least amount without side effects.

The dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction to the disease, the age, body weight, sex, history, or kind of the substance used as the active ingredient. For example, the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 100 mg / kg, preferably 1 ng to about 10 mg / kg, per adult, and the frequency of administration of the composition of the present invention is particularly It is not limited, but it can be administered once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.

In another aspect for accomplishing the above object, the present invention provides a pharmaceutical composition comprising the above-mentioned pharmaceutical composition in the form of a virus or a microorganism including a step of administering to a subject other than a human suffering from a bacterial infection or a virus accompanied by weakening of immunity in a pharmaceutically effective amount Thereby providing a method for treating infectious diseases.

The term "individual" of the present invention includes, but is not limited to, a mammal having a possibility of developing a disease accompanied by weakened immunity or having an onset of rats, livestock and the like, aquaculture fish, Except for humans.

In the method for treating a disease accompanied by the weakening of immunity of the present invention, the diseases accompanying the weakening of the immunity to be treated are the same as those described above.

The route of administration of the pharmaceutical composition for preventing or treating viral or bacterial infection according to the present invention can be administered through any ordinary route as long as it can reach the target tissue. The pharmaceutical composition of the present invention is not particularly limited, but may be administered by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, rectal administration and the like &Lt; / RTI > However, since oral extracts may denature the extract, its fractions or the nine compounds derived therefrom by gastric acid, the oral composition should be formulated so as to coat the active agent or protect it from degradation at the top . In addition, the composition may be administered by any device capable of transferring the active agent to the target cell.

As another embodiment for achieving the above object, the present invention provides a quasi-drug composition for preventing or treating a virus or bacterial infectious disease, comprising an extract or a fraction thereof as an active ingredient.

The term "quasi-drug product" used in the present invention means products that are less active than drugs, among the products used for diagnosing, treating, improving, alleviating, treating or preventing diseases of human or animal. For example, The quasi-quasi-drug means a product that is used for the treatment of diseases of humans and animals, except for the products used for medicines, which are slightly or not directly acting on the human body, , And sterilization and insecticides to prevent infectious diseases. The type and formulations of the quasi-drug composition of the present invention are not particularly limited, but may be disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.

As another embodiment for achieving the above object, the present invention provides a health functional food composition for preventing or ameliorating a virus or bacterial infectious disease comprising an extract or a fraction thereof as an active ingredient.

When the health functional food composition of the present invention is used as a food additive, the composition may be added as it is or may be used together with other food or food ingredients, and may be appropriately used according to a conventional method.

The kind of the food is not particularly limited, and includes food in a conventional sense. Non-limiting examples of foods to which the material can be added include dairy products including meats, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, ice creams, , A drink, an alcoholic beverage, and a vitamin complex.

When the health functional food composition of the present invention is a beverage composition, various flavoring agents, natural carbohydrates, and the like may be contained as additional components such as ordinary beverages. Non-limiting examples of such natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweetening agents such as dextrin, cyclodextrin; Synthetic sweetening agents such as saccharin and aspartame, and the like. The proportion of the additional component added may be appropriately determined by a person skilled in the art.

In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the health functional food composition of the present invention may contain pulp for the production of natural fruit juice, fruit drink or vegetable drink. These components may be used independently or in combination of two or more. The ratios of these additives can also be suitably selected by those skilled in the art.

As another embodiment for achieving the above object, the present invention provides a feed or feed additive for preventing or ameliorating a virus or a bacterial infection comprising an extract or its fraction as an active ingredient.

The feed additive of the present invention may be prepared by separately preparing a composition containing the extract of the present invention as a feed additive and mixing the composition with the feed or by adding the composition containing the extract as an additive .

The kind of the feed provided in the present invention is not particularly limited, and feeds conventionally used in the art can be used. Non-limiting examples of such feeds include vegetable feeds such as cereals, muscle roots, food processing busines logistics, algae, fibers, pharmaceutical buses, oils, fats, pastes or grain by-products; Animal feeds such as proteins, inorganic substances, fats, oils, fats, oils, monocellular proteins, animal plankton or foods. These may be used alone or in combination of two or more.

The feed additive of the present invention may be in a liquid or dry state, preferably in the form of a dried powder. The drying method for preparing the feed additive of the present invention in the form of a dried powder is not particularly limited and a method commonly used in the art can be used. Non-limiting examples of the drying method include air drying, natural drying, spray drying, and freeze drying. These may be used alone or in a manner that uses two or more methods together.

The feed additive of the present invention may further include other additives as required. Non-limiting examples of the above-mentioned usable additives include binders, emulsifiers, preservatives and the like which are added to prevent deterioration of feed or drinking water quality; A non-protein nitrogenous compound, a silicate, a buffer, a coloring agent, an extracting agent or an oligosaccharide to be added for the purpose of increasing the efficiency of feed or drinking water, In addition, a feed mixture or the like may be further included. These may be used alone or two or more of them may be added together.

The extract or its fraction provided by the present invention induces the activation of TLR4 and TLR7 / 8 and the production of interferon beta, thereby enhancing the TLR-mediated immune activity, thereby preventing, treating or ameliorating a virus or bacterial infection Therefore, the composition can be manufactured into various forms such as a pharmaceutical composition for preventing or treating viral or bacterial infectious diseases, a quasi-drug composition, a health functional food composition for preventing or improving viral or bacterial infectious diseases, a feed or a feed additive.

FIG. 1 is a graph showing changes in TLR4 activity according to the concentration of the extruded hot-water extract. FIG.
FIG. 2 is a graph showing changes in TLR7 / 8 activity according to the concentration of the extruded hot-water extract. FIG.
FIG. 3 is a graph showing changes in the level of interferon beta production according to the treatment time of the extruded hot-water extract. FIG.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1 : Out Preparation of extract

The head was thoroughly washed with water, shredded and pulverized with a Waring brand. To 100 g of the pulverized outflow, 5 times as much water as weight was added, and the mixture was extracted at 100 캜 for 10 hours and then filtered. This was concentrated under reduced pressure to obtain crude extract (9.8 g).

Example 2 : Out Extract TLR4 , TLR7 / 8 activation test

THP1-Blue-CD14 cells were inoculated into 96-well plates at a level of 2 × 10 5 cells / well and cultured for 3 hours. Then, the hot-water extracts obtained in Example 1 were cultured at 1, 3, 30 or 60 占 퐂 / ml, and reacted for 1 hour. After the reaction was terminated, LPS (50 ng / ml), a ligand of TLR4, or R848 (10 μg / ml), a ligand of TLR7 / 8 was treated and further reacted for 18 hours. After completion of the reaction, 20 μl of each culture supernatant was added to 200 μl of QUANTI blue reagent, and the culture supernatant of the control and the ligand were treated until the absorbance of the culture supernatant of the experimental group was about 6 to 10 times After the reaction, the absorbance at 655 nm was measured, and the measured absorbance was converted to calculate the activity level of TLR4 or TLR7 / 8 (Table 1, Fig. 1, Table 2 and Fig. 2). At this time, the negative control group was used without treatment with each ligand, and the positive control group was treated with each ligand and no extract treatment.

Changes of TLR4 activity level according to treatment level of extract sample Treatment concentration Absorbance (655 nm) TLR4 activity (%) Negative control group
Positive control group -
50 ng / ml 0.036
0.216 Extract extract 60 쨉 g / ml
30 mu g / ml
10 mu g / ml
3 mu g / ml
1 mu g / ml 0.665
0.67
0.557
0.247
0.182 280.42
275.37
213.95
20.77
-11.87

FIG. 1 is a graph showing changes in TLR4 activity according to the concentration of the extruded hot-water extract. FIG.

As shown in Table 1 and FIG. 1, it was confirmed that the extract of Arthur treated with a concentration of 60 μg / ml increased the activity of TLR4 by about 280.42%.

Changes in TLR7 / 8 activity level according to treatment level of extract sample Treatment concentration Absorbance (655 nm) TLR7 / 8 activity (%) Negative control group
Positive control group -
50 ng / ml 0.077
0.556 Extract extract 60 쨉 g / ml
30 mu g / ml
10 mu g / ml 1.631
1.597
1.261 224.1
217.02
146.9

FIG. 2 is a graph showing changes in TLR7 / 8 activity according to the concentration of the extruded hot-water extract. FIG.

As shown in Table 2 and FIG. 2, it was confirmed that the extracts treated with 60 μg / ml of the extract increased the activity of TLR7 / 8 by about 224.10%.

Example 3 : Out Induction of interferon beta production of extracts

J774A.1 cells were inoculated into a 6-well plate at a level of 2 x 106 cells per well and cultured for one day. Then, the hot-water extract obtained in Example 1 above was inoculated into a culture medium containing 60 占 퐂 / ml And the reaction was carried out for 12 hours or 24 hours, from which each culture supernatant was obtained. Interferon beta was added to 100 μl of the culture supernatant, and the mixture was reacted at room temperature for 1 hour. Then, the reaction container was washed, 100 μl of the antibody solution was added, and the reaction was allowed to proceed at room temperature for 1 hour. After the reaction was completed, the HRP solution was added and reacted for another 1 hour. After completion of the reaction, 100 μl of the TMB solution was added to the dark room, and the reaction was terminated for 15 minutes. The reaction was terminated and the absorbance at 450 nm was measured. The measured absorbance was converted to the concentration of the extruded hot- (Table 3 and Fig. 3).

Induction of Interferon β Production by Extracted Hot Water Extract sample density time Absorbance (450 nm) Interferon beta level Control group 0.660 37.84 Extract extract 60 쨉 g / ml 12 hours
24 hours 0.209
0.109 68.06
46.54

FIG. 3 is a graph showing changes in the level of interferon beta production according to the treatment time of the extruded hot-water extract. FIG.

As shown in the above Table 3, it was found that the extracts of the extracts could effectively induce the production of interferon beta.

As a result of the above results, it has been confirmed that the extract has an effect of increasing the activity of TLR4 and TLR7 / 8 by more than 200% and actively inducing the production of interferon beta. Therefore, the extract of the present invention can prevent or treat a viral or bacterial infection Effect.

From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.

Claims

A pharmaceutical composition for preventing or treating viral or bacterial infectious diseases, comprising a hydrothermal extract or a fraction thereof of rhizome of Curcuma phaeocaulis as an active ingredient.

delete

The method according to claim 1,
Wherein the fraction is a fraction obtained by applying the hot-water extract of the outflow to a method selected from the group consisting of a solvent fractionation method, an ultrafiltration fractionation method, a chromatography fractionation method, and a combination thereof.

The method according to claim 1,
Wherein said pharmaceutical composition enhances TLR-mediated immune activity and thus has the effect of preventing or treating a viral or bacterial infection.

A quasi-drug composition for preventing or treating a virus or a bacterial infection, comprising a hydrothermal extract or fraction thereof of rhizome of Curcuma phaeocaulis as an active ingredient.

Wherein the composition comprises a hydrothermal extract or fraction thereof of the rhizome of Curcuma phaeocaulis as an active ingredient.

A feed or feed additive for preventing or ameliorating a virus or bacterial infection, comprising a hydrothermal extract or a fraction thereof of the rhizome of Curcuma phaeocaulis as an active ingredient.