KR101684574B1 - Pharmaceutical compositions and health functional foods comprising Cibotium barometz J. Smith extracts for preventing or treating anticancer agent-induced of hematopoietic toxicity - Google Patents

Abstract

The present invention relates to a cibotium- baromet The present invention relates to a pharmaceutical composition for prevention and treatment of hematopoietic toxicity, which comprises an extract of Aspergillus oryzae Smith (J. Smith) extract as an active ingredient. Specifically, the extract of the present invention is effective for attenuating the efficacy of various anticancer drugs having different mechanisms, Since the bone marrow toxicity and the hematopoietic toxicity induced by the anticancer agent are effectively mitigated without accelerating the anticancer agent, the extract can be effectively used as an active ingredient of a pharmaceutical composition for the prevention and treatment of anticancer drug induced hematopoietic toxicity.

Description

The present invention relates to a pharmaceutical composition and a health functional food for preventing and treating anticancer agent-induced hematopoietic toxicity comprising an extract of Gucci extract as an active ingredient, and a health functional food comprising an anticancer agent-induced hematopoietic toxicity of Cibotium barometz J. Smith extracts,

The present invention relates to a cibotium- baromet J. Smith) extract as an active ingredient. The present invention also relates to a pharmaceutical composition for preventing and treating cancer-induced hematopoietic toxicity.

Cancer is controversial not only in Korea but also in the United States, Japan, and other countries, and it accounts for more than half of deaths in large hospitals (Life Science Trend, Biotechnology Research Institute, 3: 55, 1995; Tsuruo, Cancer chemotherapy, Seo Kwang Seolim, 351, 1991).

Surgical surgery, radiation therapy, and chemotherapy are most commonly used for the treatment of these cancers. Among them, the development of anticancer drugs as chemotherapy is the core of researches on the development of biotechnology-related technology, and many attempts have been made using various kinds of cancer cells. However, until now, there has been no anticancer drug as a true therapeutic agent. Only drugs that help prolong life have been developed. In addition, radiotherapy and chemotherapy have serious problems of deterioration of the quality of life of the patients due to their toxicity and side effects, because the current treatment does not clearly distinguish between normal cells and cancer cells. Radiation therapy or chemotherapy not only selectively acts on cancer cells but also damages normal cells, especially bone marrow tissues and gastric mucosal tissues which are active in cell division. Therefore, the most frequent side effects include bone marrow hematopoietic disorders, gastrointestinal disorders, alopecia It involves side effects.

In recent years, interest in Chinese medicine has been increasing as a method for reducing side effects of chemotherapy and radiotherapy and increasing the cancer treatment rate, and a therapeutic method by combination of East and West medicine has been actively studied. Thus, the effect of licorice extract on relieving cardiotoxicity induced by doxorubicin, which is an anticancer drug (Choi HJ, et al . Exp Biol Med (2008) 233: 1554-1560) and mixed extracts of medicinal herbs tinge study on the efficacy and safety of inhibiting hematopoietic toxicity due to fluorouracil in safflower tang (Fluorouracil) (GA Moon, et al . Kor. J. Pharmacogn. (2004) 35 (2): 122-127).

In addition, Korean Patent No. 10-0697212 discloses a hematopoietic promoter for treating side effects caused by the administration of an anticancer drug, which comprises an extract of a mixed herbal medicine of Hwanggi and Angelica gigas as active ingredients. In Korean Patent No. 10-1398076, Or a soybean-derived phosphatidylcholine as an active ingredient, and Korean Patent Registration No. 10-0501039 discloses a composition for inhibiting the renal toxicity, hematopoietic immunotoxicity, and digestive toxicity of a cisplatin anticancer agent Discloses an extract of Grifola frondasa .

However, there has been no report on hematopoietic toxicity caused by anticancer drugs having various mechanisms, and herbal medicines and therapies exhibiting inhibitory effects at the same time. Therefore, a composition for improving the adverse effects of chemotherapeutic treatment There is a continuing need for research for the use as a drug.

Cibotium barometz J. Smith, Cibotii Rhizoma). It is a herbal medicine for rootstocks in Korea and China. It is made in Korea and China for strengthening the back and legs, facilitating movement of joints, and relieving low back pain, arthritis, It is treated and improved renal function, and it is used for urination, sexual dysfunction, etc. Antioxidant activity, antimicrobial, and hemostatic effects have been reported as pharmacological effects. In addition, it is known to be effective for osteoporosis, lumbar disc, anal pain and the like.

Accordingly, the present inventors have made efforts to develop a therapeutic agent for hematopoietic toxicity induced by an anticancer agent from a medicinal plant. As a result, the present inventors have found that the hydrothermal extract of Gucci is an anticancer agent having various mechanisms such as Paclitaxel, Irinotecan and Doxorubicin The present invention provides a method for preventing and treating hematopoietic toxicity, which comprises administering to a patient in need thereof a therapeutically effective amount of a hematopoietic agent for preventing and treating hematopoietic toxicity, The present invention can be used as an active ingredient of the composition.

Korean Patent No. 10-0697212 Korean Patent No. 10-1398076 Korean Patent No. 10-0501039

Choi HJ, et al. Exp Biol Med (2008) 233: 1554-1560 GA Moon, et al. Kor. J. Pharmacogn. (2004) 35 (2): 122-127 Mai et al. Advanced Pharmaceutical Bulletin, 2012, 2 (1), 107-114

It is an object of the present invention to provide a pharmaceutical composition for prevention and treatment of anticancer drug-induced hematopoietic toxicity which can alleviate bone marrow toxicity and hematopoietic toxicity induced by an anticancer drug without weakening the efficacy of the anticancer drug or promoting the growth of cancer cells To provide a composition.

In order to achieve the above object, the present invention provides a cibotium- baromet J. Smith) extract as an active ingredient. The present invention also provides a pharmaceutical composition for preventing and treating hematopoietic toxicity.

In addition, the present invention provides a health functional food for preventing and improving hematopoietic toxicity, which contains a citrus extract as an active ingredient.

The extract of the present invention effectively alleviates the effects of various anti-cancer drugs having different mechanisms or does not promote the growth of cancer cells, and at the same time effectively alleviates bone marrow toxicity and hematopoietic toxicity induced by anticancer drugs. Therefore, And may be useful as an active ingredient of a pharmaceutical composition for the prevention and treatment of hematopoietic toxicity.

FIG. 1 is a view showing cell viability of hematopoietic stem cells in a medium treated with various anti-cancer agents.
FIG. 2 is a graph showing the effects of various water extracts of various concentrations on bone marrow cell proliferation.
Fig. 3 shows a colony of hematopoietic stem cells cultured by treatment with hot water extract.
FIG. 4 is a chart for confirming whether or not the mulberry extract has an effect of alleviating inhibition of growth of bone marrow cells by an anticancer agent.
FIG. 5 is a chart for confirming the effect of the hot water extract on the anticancer activity of an anticancer drug treated with cancer cells.

Hereinafter, terms of the present invention will be defined.

As used herein, the term " hematopoietic toxicity " refers to the damage or impairment of the organ or cell of the hematopoietic system resulting in a hematopoietic dysfunction, in particular a hematopoietic disorder or a dysfunction of red blood cells or immune system cells such as leukocytes. Preferably, hematopoiesis in the bone marrow or function of the immune system is affected by hematopoietic toxicity. Therefore, it is preferable that the hematopoietic toxicity generally includes bone marrow toxicity, anemia and neutropenia, and more preferably, it is induced by administration of a chemical compound or a drug or a result of such administration. In the present invention, the chemical compound or drug is preferably an anticancer agent.

Hereinafter, the present invention will be described in detail.

The present invention relates to a cibotium- baromet J. Smith) extract as an active ingredient. The present invention also provides a pharmaceutical composition for preventing and treating hematopoietic toxicity.

Preferably, the extract is extracted with water, C ₁ to C ₂ lower alcohol or a mixture thereof as a solvent, and the lower alcohol is preferably ethanol or methanol.

Preferably, the extract is prepared by a manufacturing method comprising the following steps, but not limited thereto:

1) extracting the extract by adding an extraction solvent to the extract;

2) filtering the extract of step 1); And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In this method, the step 1) may be used without limitation, such as cultivated or commercially available. It is preferable that the bulb is a root stem of a gold bulb chuck.

In the above method, a conventional method such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction can be used as a method for extracting the extract. It is preferable that the extraction solvent is added by 2 to 20 times the amount of the dried extract. The extraction temperature is preferably 20 to 50 DEG C, but is not limited thereto. The extraction time is preferably 10 to 100 hours, more preferably 24 to 96 hours, and most preferably 72 hours, but not always limited thereto.

In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in step 3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.

In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in step 3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.

Preferably, the hematopoietic toxicity is induced by an anticancer agent, and the anticancer agent includes, but not limited to, antitumor antibiotics, topoisomerase inhibitors, or taxane drugs, , Pharmacology, and biochemically available anticancer drugs.

The antineoplastic antibiotic may be selected from the group consisting of actinomycin D, bleomycin sulfate, daunomycin, daunorubicin, doxorubicin, epirubicin, It is preferably one or more selected from the group consisting of idarubicin, mitomycin, mitomycin-C and mitramycin, more preferably doxorubicin, but is not limited thereto Do not.

The topoisomerase inhibitor may be selected from the group consisting of irinotecan, camptothecin, novobiocin, epirubicin, dactinomycin, amsacrine, teniposide, and etoposide. It is more preferably one selected from the group consisting of irinotecan, but is not limited thereto.

The taxane-based drug is preferably one or both of paclitaxel and docetaxel, more preferably paclitaxel, but is not limited thereto.

In a specific example of the present invention, the present inventors confirmed the hematopoietic toxicity exhibited by various anticancer agents currently used, and found that they exhibit hematopoietic toxicity commonly in anticancer agents having various mechanisms (see FIG. 1).

In addition, the inventors of the present invention have confirmed the effect of producing the hot water extract of the present invention on the proliferation of bone marrow cells. As a result, it was confirmed that the increase of the hematopoietic stem cells and the colony size were increased when the hot water extract was treated And Fig. 3).

In addition, the inventors of the present invention found that the extracts of Kookjak extract showed the effect of alleviating the inhibition of growth of bone marrow cells by the anticancer agent. As a result, when the anti-cancer agent was administered at a concentration causing bone marrow toxicity, (See FIG. 4). On the other hand, it was confirmed that the extract from the hot water extract did not weaken the efficacy of the anticancer agent or promote the growth of cancer cells against cancer cells treated with the anticancer agent (see FIG. 5 ).

Therefore, the extract of the present invention effectively alleviates the efficacy of various anticancer drugs having different mechanisms or promotes the growth of cancer cells, and at the same time effectively alleviates bone marrow toxicity and hematopoietic toxicity induced by anticancer drugs, And can be usefully used as an active ingredient of a pharmaceutical composition for the prevention and treatment of anticancer drug-induced hematopoietic toxicity.

The compositions of the present invention may be of various oral or parenteral formulations. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances or preservatives are included .

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations or suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol, gelatin and the like can be used.

The composition of the present invention may be administered orally or parenterally, and it is preferable to select the intraperitoneal, rectal, rectal, intravenous, intramuscular, subcutaneous, intrauterine or intracerebral injection methods for parenteral administration, It is used for external skin.

The composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity, The dose is 0.01 to 1000 mg / kg, preferably 30 to 500 mg / kg, more preferably 50 to 300 mg / kg, and can be administered 1 to 6 times a day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.

The composition of the present invention is preferably used in combination with an anticancer agent as a method of using chemotherapy, but may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, and a biological response modifier Can be used.

In addition, the present invention provides a health functional food for preventing and improving hematopoietic toxicity, which contains a citrus extract as an active ingredient.

The extract is preferably extracted with water, ethanol or a mixture thereof as a solvent.

It is preferable that the hematopoietic toxicity is induced by an anticancer agent, and the anticancer agent includes all anticancer drugs including clinical, pharmaceutical, biomedical, including, but not limited to, antitumor antibiotics, do.

The extract of the present invention effectively alleviates the effects of various anti-cancer drugs having different mechanisms or does not promote the growth of cancer cells, and at the same time effectively alleviates bone marrow toxicity and hematopoietic toxicity induced by anticancer drugs. Therefore, Can be usefully used as an active ingredient of a health functional food for prevention and improvement of hematopoietic toxicity.

In the present invention, the term " health functional food " is produced by using raw materials or ingredients (functional raw materials) having functions useful for nutrients or human body which are likely to be deficient in daily eating, It is meant to include all health foods in the usual meaning, but not limited to, food, which is defined by the Director of the Food and Drug Administration.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including dairy products, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, Beverages, alcoholic beverages and vitamin complexes, dairy products, and dairy products, all of which include health functional foods in a conventional sense. The health functional food may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and rings, but is not limited thereto and may be manufactured and processed in any form according to the law.

The citrus extract of the present invention can be directly added to the food or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). Generally, the amount of the compound in the health food may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term consumption intended for health or hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

The health functional beverage composition of the present invention is not particularly limited to the other ingredients other than the above-mentioned compounds as essential ingredients in the indicated ratios and may contain various flavors or natural carbohydrates as additional ingredients such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 of the composition of the present invention.

In addition to the above, the extract of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and heavies (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the extract of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so important, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples, Experimental Examples and Preparation Examples.

However, the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples, Experimental Examples and Preparation Examples.

< Example  1> Caliber ( Cibotium baromet J. Smith ) Preparation of extract

<1-1> Caliber Heat number  Preparation of extract

In order to carry out the experimental example of the present invention, a hot water extract of Gucci was prepared.

Specifically, the beaker was dried and pulverized, then extracted with hot water and concentrated under reduced pressure to obtain a hot water extract.

<1-2> Caliber  Preparation of methanol extract

The beaker was dried, pulverized, extracted with 99.9% methanol and concentrated under reduced pressure to obtain a methanol extract.

< Experimental Example  1> Various anticancer drugs Hematemesis  Identification of cytotoxicity to cells

To confirm the hematopoietic toxicity of various anticancer agents currently used, the cell viability of hematopoietic stem cells was confirmed in the medium treated with the anticancer agent.

Specifically, bone marrow cells (myelocytes) were isolated from the femur of mice. Then, recombinant murine stem cell factor (rm) stem cell factor, rm IL-3, human-derived recombinant human IL-6, and human erythropoietin (methocult GF M3434) medium containing rh erythropoietin were added to each of the anticancer agents as shown in Table 1 below, and the separated bone marrow cells were cultured for 7 days to induce the growth of hematopoietic stem cells. Respectively. Seven days later, the grown hematopoietic stem cells were obtained and the effect of the anticancer drug on the growth and differentiation of hematopoietic stem cells was observed by performing a colony forming unit assay (CFU assay).

Anticancer agent and its concentration for confirming cytotoxicity to hematopoietic stem cells Anticancer drug (concentration) Paclitaxel (nM) Irinotecan (μM) Doxorubicin (μM)   0.0   0.0  0.0   1.0   1.0  0.1   3.0   5.0  0.5  10.0  10.0  1.0  50.0  50.0  5.0 100.0 100.0 10.0

As a result, as shown in FIG. 1, it was confirmed that hematopoietic toxicity was commonly exhibited in anticancer drugs having various mechanisms such as Paclitaxel, Irinotecan, and Doxorubicin (FIG. 1).

< Experimental Example  2> Caliber Heat number  Identification of promoting effect of extract on bone marrow cell proliferation

Bone marrow cells were cultured and cultured in medium supplemented with hot water extracts.

Specifically, bone marrow cells were isolated from the femur of the mouse. Then, the hot water extract prepared in Example 1 was added at 25, 50 or 100 ㎍ / ml to the medium of Methocult GF M3434 containing rm stem cell factor, rm IL-3, rh IL-6 and rh erythropoietin. Ml, respectively, and the separated bone marrow cells were cultured for 7 days to induce the growth of hematopoietic stem cells. Seven days later, grown hematopoietic stem cells were obtained and CFU analysis was performed to confirm the growth of hematopoietic stem cells. As a negative control group, water was treated as a vehicle instead of hot water extract, and the same method as described above was performed.

As a result, as shown in FIG. 2 and FIG. 3, when the bone marrow cells of mice were treated with various concentrations of hot water extract, it was confirmed that a slight increase of hematopoietic stem cells was observed at a low concentration of 25 μg / ml 2), and the size of the generated CFU also increased in proportion to the treatment concentration (FIG. 3).

< Experimental Example  3> induced by anticancer drugs To bone marrow toxicity  About Caliber Heat number  Identification of the efficacy of the extract

In order to confirm whether or not the extracts of Kookjak showed the effect of alleviating the inhibition of growth of bone marrow cells by the anticancer drug, the bone marrow cells of the mice were treated with various concentrations of the anti - cancer drugs and the water extracts of various concentrations to induce bone marrow toxicity.

Specifically, 50 nM of paclitaxel, 10 μM of irinotecan or 100 nM of doxorubicin was added to GF M3434 medium containing the same composition as in Experimental Example 2, and bone marrow cells isolated from the femurs of mice were cultured for 7 days , And the growth of hematopoietic stem cells was confirmed by performing CFU analysis. As a negative control, water was treated as a vehicle in the medium containing no anticancer agent instead of hot water extract, and the same method as described above was carried out.

As a result, as shown in Fig. 4, when the growth of the hematopoietic stem cells was induced by treating the extract, the colonies of the hematopoietic stem cells were statistically significantly increased, Regardless of the mechanism, it was confirmed that Koochik extract showed a mitogenic effect on bone marrow toxicity (FIG. 4).

< Experimental Example  4> Caliber Heat number  Effect of extracts on anticancer efficacy

The effect of the extract from hot water extract on the anticancer activity of the anticancer agent is confirmed because it does not weaken the efficacy of the anticancer drug or accelerate the growth of the cancer cell during the administration of the anticancer agent, .

Specifically, A549, a human lung cancer cell line, was purchased from the American Type Culture Collection (ATCC; trade name: CLL-185), and 5 x 10 ³ cancer cells were plated on a 96- And then cultured in a humidified incubator of 5% CO ₂ for 24 hours. After cultivation, 5, 10, 25, 50 or 100 占 퐂 / ml were added to the culture medium and 50 nM of paclitaxel, 100 nM of paclitaxel, 10 占 퐇 of irinotecan, 50 占 퐇 of irinotecan, 500 nM of doxorubicin or After treatment with 1 μM doxorubicin, the cells were further cultured for 48 hours. After 48 hours, the culture medium was removed and 100 μl of 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- -Tetrazolium salt (MTS, 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H- , And the absorbance was measured at 490 nm. As a negative control group, A549 cells cultured in the same manner as in the above method in a medium not containing both an anticancer agent and a mulberry extract were used. Based on the absorbance of the negative control group, the relative proliferation index) was measured. As a positive control, A549 cells were cultured in the same manner as described above in a culture medium in which only anti-cancer agent was treated, without adding Caulchus extract.

As a result, as shown in FIG. 5, it was confirmed that the survival rate of the cancer cells was decreased in all of the medium treated with the anticancer agent, and this decrease appeared regardless of whether the extract was treated or not, and the extract from the hot water extract inhibited the anti- (Fig. 5).

< Manufacturing example  1> Preparation of pharmaceutical preparations

<1-1> Sanje  Produce

0.1 g &lt; RTI ID = 0.0 &gt;

Lactose 1.5 g

Talc 0.5 g

The above ingredients were mixed and filled in an airtight container to prepare powders.

<1-2> Manufacture of tablets

0.1 g &lt; RTI ID = 0.0 &gt;

Lactose 7.9 g

Crystalline cellulose 1.5 g

0.5 g of magnesium stearate

After mixing the above ingredients, tablets were prepared by direct tableting method.

<1-3> Preparation of capsules

0.1 g &lt; RTI ID = 0.0 &gt;

Corn starch 5 g

4.9 g of carboxycellulose

After mixing the above components to prepare a powder, the powder was filled in a hard capsule according to a conventional preparation method of a capsule to prepare a capsule.

&Lt; 1-4 > Preparation of injection

0.1 g &lt; RTI ID = 0.0 &gt;

Sterile sterilized water for injection

pH adjuster

(2 ml) per ampoule according to the usual injection preparation method.

<1-5> Liquid  Produce

0.1 g &lt; RTI ID = 0.0 &gt;

10 g per isomer

5 g mannitol

Purified water quantity

Each component was dissolved in purified water in accordance with a conventional method for producing a liquid agent, and the lemon flavor was added in an appropriate amount, followed by mixing the above components. Then, purified water was added to adjust the total amount to 100, and the solution was filled in a brown bottle and sterilized to prepare a liquid preparation.

< Manufacturing example  2> Manufacture of health food

<2-1> Production of flour food

0.5 to 5.0 parts by weight of the mugwort extract of the present invention was added to wheat flour, and the mixture was used to prepare bread, cake, cookies, crackers and noodles.

<2-2> soup  And juicy ( gravies )

0.1 to 5.0 parts by weight of the mugwort extract of the present invention was added to the soup and the juice to prepare health promotion meat product, noodle soup and juice.

<2-3> Ground Beef  Produce

10 parts by weight of the extract of the present invention was added to ground beef to prepare ground beef for health promotion.

<2-4> Dairy products ( dairy products )

5-10 parts by weight of the extract of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

<2-5> Solar  Produce

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh.

Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.

The crude extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and drying with a hot air drier, and pulverized to a size of 60 mesh with a pulverizer to obtain a dry powder.

The above-prepared cereals, seeds, and citrus extract of the present invention were prepared in the following proportions.

(30 parts by weight of brown rice, 15 parts by weight of yulmu, 20 parts by weight of barley)

Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)

(3 parts by weight) of the present invention,

(0.5 part by weight),

(0.5 parts by weight)

<2-6> Production of health supplement foods

100 mg of the extract of the present invention

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

The composition ratio of the above-mentioned vitamin and mineral mixture is relatively mixed with a suitable ingredient for health food. However, the compounding ratio may be arbitrarily changed, and the above ingredients may be mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

< Manufacturing example  3> Manufacture of health drinks

100 mg of the extract of the present invention

Citric acid 100 mg

100 mg of oligosaccharide

2 mg of plum concentrate

100 mg taurine

Purified water was added to 500 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered to obtain a sterilized 1 liter container which was sealed and sterilized, &Lt; / RTI &gt;

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (11)

A pharmaceutical composition for preventing and treating hematopoietic toxicity induced by an anticancer agent containing an extract of Cibotium barometz J. Smith as an active ingredient. The pharmaceutical composition for preventing and treating hematopoietic toxicity according to claim 1, wherein the extract is extracted with water, C ₁ to C ₄ lower alcohol or a mixture thereof as a solvent. 3. The pharmaceutical composition according to claim 2, wherein the lower alcohol is ethanol or methanol. 3. The pharmaceutical composition according to claim 2, wherein the lower alcohol is ethanol or methanol. delete The anticancer agent according to claim 1, wherein the anticancer agent is antitumor antibiotics, topoisomerase inhibitor, or taxane-based drug. A pharmaceutical composition for therapeutic use. 6. The method of claim 5, wherein the antineoplastic antibiotic is selected from the group consisting of actinomycin D, bleomycin sulfate, daunomycin, daunorubicin, doxorubicin, wherein the anticancer agent is at least one selected from the group consisting of epirubicin, idarubicin, mitomycin, mitomycin-C and mitramycin. A pharmaceutical composition for the prevention and treatment of toxicity. 6. The method of claim 5, wherein the topoisomerase inhibitor is selected from the group consisting of irinotecan, camptothecin, novobiocin, epirubicin, dactinomycin, , Amsacrine, teniposide, and etoposide. The pharmaceutical composition for preventing and treating hematopoietic toxicity according to claim 1, wherein the composition is at least one selected from the group consisting of amoxicillin, amsacrine, teniposide, and etoposide. [Claim 6] The pharmaceutical composition according to claim 5, wherein the taxane-based drug is paclitaxel or docetaxel, or both. A health functional food for prevention and improvement of hematopoietic toxicity induced by an anticancer agent containing Kookjak extract as an active ingredient. [Claim 11] The health food according to claim 9, wherein the extract is extracted with water, ethanol or a mixture thereof as a solvent. delete

Images