KR20040000757A - Composition for Suppressing the toxicity of anti-cancer treatment - Google Patents

Abstract

PURPOSE: Provided is a composition of medicinal plants having inhibition effect on the adverse side effect of anti-cancer treatment, such as radiotherapy and chemotherapy for cancer. The composition shows inhibition effect on hematopoietic toxicity. CONSTITUTION: A composition of medicinal plants having inhibition effect on the adverse side effect of radiotherapy and chemotherapy for cancer is characterized by comprising 7-20 parts by weight of steamed and dried Rehmannia glutinosa, 5-15 parts by weight of Angelica gigas Nakai, 5-15 parts by weight of Cnidium officinale, 5-15 parts by weight of Paeonia japonica Miyabe et Takeda, 3-10 parts by weight of Cormus offcinalis, 1.5-5 parts by weight of Paeonia suffruticosa Andrews, 0.5-2.0 parts by weight of Carthamus Tinctorius and 1-3 parts by weight of Glycyrrhiza uralensis Fisch.

Description

Composition for Suppressing the toxicity of anti-cancer treatment

The present invention relates to a herbal composition having an effect of suppressing side effects of chemotherapy, and more particularly, to inhibit side effects of fluorotherapy agent 5-fluorouracil (FU) and irradiation, which are currently the most clinically available. It relates to a herbal composition having efficacy.

Decades ago, many excellent anticancer agents and anticancer therapies have been developed by chemical synthesis or natural product separation methods. Recently, SK has developed SunPlae chemotherapeutic agents as the first domestic drug in Korea. These efforts have dramatically improved the rate of cancer treatment over the past decades, but existing cancer therapies that focus solely on the elimination of local cancer lesions have caused a major problem of poor quality of life for patients. There is an urgent need to improve the deterioration of quality of life.

The chemotherapeutic agent 5-fluorouracil (FU) was first synthesized in 1957 and is still widely used in clinical practice (Duschinsky et al., 1957). 5-Fluorouracil, an anticancer agent that converts into active nucleotides in cancer cells and inhibits thymidylate synthase, inhibits DNA synthesis of the cells, breast cancer, colon cancer, rectal cancer, gastric cancer, pancreatic cancer, esophageal cancer, liver cancer, head and neck cancer, It is widely used clinically for bladder cancer and is also used topically for skin cancer. Hematopoietic toxicity is known as a dose-limiting side effect. Other side effects are severe gastrointestinal side effects such as severe gastritis, esophagitis, proctitis, and diarrhea, and hyperpigmentation of the skin is often reported (Skeel, 1999b). . In addition, 5-Fluorouracil has been shown to reduce hematopoietic toxicity, such as decreased white blood cell counts, decreased intestinal mucosal sucrase activity, digestive toxicity such as diarrhea, spleen weight loss, and lymphocyte reduction. Toxicity has been reported (Kumura and Okuda, 1999).

Accordingly, it is an object of the present invention to provide a herbal composition having an inhibitory effect of side effects without affecting the anticancer efficacy of anticancer agents and radiation.

1 is a graph showing the effect of the composition of the invention on the anticancer efficacy of an anticancer agent.

Figure 2 is a graph showing the effect on the weight of the spleen in combination with the composition of the present invention and an anticancer agent.

Figure 3 is a graph showing the effect on white blood cells when the composition of the present invention and an anticancer agent.

Figure 4 is a graph showing the effect on red blood cells when the composition of the present invention and an anticancer agent.

Figure 5 is a graph showing the effect on body weight when combined with the composition of the present invention and an anticancer agent.

6 and 7 are image analysis results and comparative graphs showing the degree of recovery of IL-2 gene expression in combination with the composition of the present invention and anticancer agents.

8 and 9 are image analysis results and comparative graphs showing the degree of recovery of IFN-γ gene expression in combination with the composition of the present invention and anticancer agents.

10 is a tissue micrograph showing the expression pattern of IL-2 mRNA in the spleen tissue when using the composition of the present invention and anticancer agent.

11 is a graph showing the comparison of treatment completion rate at the time of radiotherapy alone and the combination of radiation and the composition of the present invention.

12 is a graph showing the effect on leukocytes in combination with radiation and the composition of the present invention.

Figure 13 is a graph showing the effect on platelets when the composition of the present invention in combination with radiation.

Figure 14 is a graph showing the effect on leukopenia when combined with radiation composition of the present invention.

The purpose of the present invention is the dry weight ratio of Sukji Hwang 7-20 parts by weight, Angelica 5-15 parts by weight, Cheongung 5-15 parts by weight, Baekjak 5-15 parts by weight, Cornus 3-10 parts by weight, neck skin 1.5-5 parts by weight , 1.5-5 parts by weight of wolfberry, 0.5-2.0 parts by weight of safflower, and 1-3 parts by weight of licorice.

In animal experiments in combination with chemotherapy and the composition of the present invention, the effect of the composition of the present invention on the side effects of 5-fluorouracil (FU) was confirmed. After 5-fluorouracil (FU) treatment, it was confirmed that the leukocyte and platelet levels decreased significantly by oral administration of the composition of the present invention. Analysis of the expression levels of interleukin-2 (IL2) and interferon-γ (IFN-γ) by RT-PCR showed that the composition of the present invention restored the expression of these immunofactors reduced by 5-FU. It was. The mRNA expression level of IL2 in the spleen determined through in situ hybridization also showed a marked increase in the expression level upon treatment of the composition of the present invention. On the other hand, the anti-cancer effect showed the same effect in the treatment of the composition of the present invention at various doses as compared to the 5-FU treatment alone. The composition of the present invention is useful for selectively inhibiting side effects of the hematopoietic system while maintaining the anticancer efficacy of 5-FU.

In animal experiments in combination with radiation therapy and the composition of the present invention, the inhibitory effect of the composition of the present invention on hematopoietic toxicity of irradiation was investigated. Leukocytes, erythrocytes, and platelets all showed a sharp decrease with time after irradiation. When 10 Gy of the mice was irradiated, a marked decrease was observed after 5 days of leukocytes and platelets and 12 days of red blood cells. Following oral administration of the compositions of the present invention, a tendency to recover leukocytes, erythrocytes, platelets was observed.

In the clinical trial using the combination of the radiation therapy and the composition of the present invention, a comparison between the radiation alone group and the combination of the radiation and the composition of the present invention showed a marked increase in treatment completion rate and a marked reduction in leukopenia in the combination group.

The present invention will be described in more detail with reference to the following Examples.

Experimental material

Herbal medicine was purchased from the medicinal herb specified in the country of origin. All of the nine Chinese herbs were purchased domestically, except for two, which were not produced in Korea, and the other two were grown and harvested in Sichuan, China. The herbal medicines purchased were immediately extracted and used. 5-Fluorouracil was purchased from Sigma Chemical (St. Louis, Mo., USA) and dissolved in 0.85% saline immediately prior to daily use.

Cell Culture and Laboratory Animals

1. Cell Culture

The cell line B16-BL6 used in the examples of the present invention is described in I.J., MD Anderson Cancer Center (Texas, USA). It was provided by Dr. Fidler and incubated in DMEM medium containing 5% fetal bovine serum and used within 30 passage numbers.

3-2. Laboratory animals

Four-week old C57BL / 6 mouse males were purchased from Daehan Biolink and acclimated to the animal nursery environment for one week and then used for anticancer efficacy and side effect inhibition experiments.

Example 1 Preparation of Herbal Medicine Composition

Dried Sookji sulfur 13.3g, Angelica 10g, Cheongung 10g, Baekjak 10g, Cornus 6.7g, Bark skin 3.3g, Wolfberry 3.3g, Safflower 1.3g, Licorice 2g, 600ml of purified water was added for 1 hour at 130 ℃ for 3 hours. Extraction was carried out at a pressure of 2 kgf / cm ² . The pressure initially increased and then gradually decreased. The extract was filtered through a mesh, the precipitate was removed, frozen at −70 ° C., and then freeze-dried (Ilsin, Bondiro) to obtain an extract from which the solvent was completely removed at −55 ° C. and 10 mTorr. The extract thus obtained was lyophilized, pulverized into a medicine bowl, powdered and stored in a sealed tube.

Example 2 Determination of Efficacy of Inhibition of Adverse Chemotherapy Agents

The effect of inhibiting the side effects of 5-fluorouracil (FU), currently the most widely used anticancer agent, was measured by modifying the method of Sugiyama et al. (1995a).

Each experimental group consisted of 10 animals. Divide the C57BL / 6 mice into groups of 10 per group, shave the right flank, and then per B16-BL6 melanoma cells To Cells were injected subcutaneously in a volume of 0.1 ml. After 7 days, a clear tumor was formed on the skin, and each mouse was intraperitoneally administered with 5-fluorouracil once, followed by oral administration of the herbal medicine once daily for 7 to 9 days using zonde. Chinese medicine was orally administered with oral zonde at various doses such as 0.5, 1, 2, 5 and 10 times based on human dose. After fasting for one day and weighing the anesthetized mouse the next day, blood was collected from the heart and received in a tube containing a small amount of 1.4% K ₂ EDTA solution, and then red blood cell (RBC) WBC), platelet (PLT) was measured. Organ weights including the spleen and tumor weights were measured.

Statistical processing of the experimental results was performed by Duncan test as one-way batch analysis and post test using the SPSS program (7.5 for Windows).

1. Anatomy and tissue treatment

The animal was anesthetized with ether and then opened, blood was collected from the heart, the spleen was extracted and weighed. After freezing on dry ice, the cryostat (Leica, Germany) was used to have a thickness of 16㎛. Continuous coronal sections were prepared.

2. In situ hybridization

The slides prepared with the frozen slicer were fixed with 4% paraformaldehyde solution, and then reacted with proteinase K for 10 minutes. After washing twice with 0.2% RNAse blocked DW, it was again fixed. The prepared probe was diluted in a hybridization buffer, smeared on a fixed tissue, reacted at 85 ° C. for 10 minutes, and then reacted at 37 ° C. for 16 hours. The reacted tissues were washed with PBS containing 0.1% Tween 20 and reacted with Strepto-avidin Horseadish peroxidase conjugase for 20 minutes, followed by another 20 minutes with anti-fluorescein-Biotinyl ated.

The degree of reaction was measured by the degree of brown reaction by diaminobenzidine (DAB), and the probes were as follows.

▶ IL2 5 'TGT GCT TCC GCT GTA GAG CT 3'

IL2 (Interleukin-2) mRNA in the spleen was brown by DAB, and was stained with Mayer's hematoxylin solution and observed by light microscopy.

3. Total RNA Isolation

Total RNA was isolated from the spleen by guanidinium-thiocyanate using Triazol Reagent (Gibco BRL, Gaithersburg, MD). First, the extracted spleen tissue was pulverized in the presence of liquid nitrogen, and then, 1 ml of Trizol reagent and 200 ul of chloroform were added and completely mixed, followed by centrifugation to obtain a supernatant. The same amount of phenol: chloroform (1: 1) was added to the supernatant, and the mixture was centrifuged, and then 0.6 times of isopropanol was added to the supernatant to precipitate and total RNA was isolated.

4. Measurement of gene expression change by RT-PCR

In order to observe the expression patterns of IL2 gene and IFN-γ gene, IL2 gene fragment and IFN-γ gene fragment were amplified by reverse transcription polymerase chain reaction (RT-PCR) method using Oligonucleotide primers. Β-Actin gene fragment was used as internal control. Each primer was as follows.

Gene name primer site primer sequence IL2 senseantisense 5 'AGA TGA ACT TGG ACC TCT GCG 3'5' GGG CTT GTT GAG ATG ATG CTT TG 3 ' IFN-γ senseantisense 5 'AGC GGC TGA CTG AAC TCA GAT TGT AG 35' GTC ACA GTT TTC AGC TGT ATA GGG 3 ▶ β -Actin senseantisense 5 'GTG CTA TGT TGC TCT AGA CTT CGA G 3'5' AGG AGC AAT GAT CTT GAT CTT CAT G 3 '

Oligonucleotide primers were prepared by Bioneer (Korea), and RT-PCR was performed using Accupower RT-PCR premix. (Bioneer, Korea). For RT-PCR, PCR system 2700 (Perkin-Elmer, U.S.A.) was used after adding 0.5 ug of total RNA, 20 pmol of sense primer, and 20 pmol of antisence primer to RT-PCR premix.

RT-PCR conditions are as follows.

IL2

42 ℃, 60min → 94 ℃, 5min → (94 ℃, 1min → 63 ℃, 1min → 72 ℃, 1min) (50cycle) → 72 ℃, 10min → 4 ℃

IFN-γ

42 ℃, 60min → 94 ℃, 5min → (94 ℃, 1min → 55 ℃, 1min → 72 ℃, 1min) (30cycle) → 72 ℃, 10min → 4 ℃

β-Actin

42 ℃, 60min → 94 ℃, 5min → (94 ℃, 1min → 55 ℃, 1min → 72 ℃, 1min) (30cycle) → 72 ℃, 10min → 4 ℃

Quantification of the PCR results was performed by using an image analyzer (IMT (VT) Morphology Program) to measure the intensity of the band with gray scale values according to brightness.

5. Results

5-1. Effect of the composition of the present invention on anticancer efficacy

In anticancer efficacy by tumor weight measurement, there was no difference from 5-fluorouracil (FU) administration group. The composition of the present invention (composition of Example 1 hereinafter abbreviated as KH) is 5-fluorouracil ( FU) did not affect the anticancer efficacy. The results are published in Table 1 below and in FIG. 1.

Table 1

Group Control FU FU + 0.5KH FU + 1KH FU + 5KH tumor (g) 2.57 ± 0.65 ^a 1.47 ± 0.27 ^b 1.48 ± 0.62 ^b 1.58 ± 0.40 ^b 1.54 ± 0.36 ^b

5-2. Effect on Spleen Weight Reduction

The effect of the composition of the present invention on the weight of the spleen, a hematopoietic immune organ of mice, was measured. It was observed that the compositions of the present invention significantly recovered the weight of the spleen reduced by administration of 5-FU. The results are published in Table 2 below and in FIG. 2.

TABLE 2

Group Control FU FU + 1KH FU + 10KH spleen (× g) 4.96 ± 0.36 ^a 3.76 ± 0.50 ^b 4.45 ± 0.21 ^c 4.25 ± 0.21 ^bc

5-3. Effect on hematopoietic toxicity

It was observed that platelet (PLT) levels decreased by 60% of the control group when 5-FU alone was administered (FIG. 3, Table 3). Platelet levels in the combination treatment of 5-FU and the composition of the present invention was 13.9 (Human Dose) in the composition of the present invention according to the dose of the composition of the present invention compared to the 5-FU alone group. HD showed a recovery of 42.6% in the composition of the present invention, it was confirmed that the platelet level is restored according to the concentration of the composition of the present invention. The statistical significance of the 5-FU alone treatment group also appeared in the statistical results.

Leukocyte (WBC) levels were observed to decrease by 48.3% of the control group when 5-FU alone. The leukocyte count in the combination of 5-FU and the composition of the present invention was 51.2% in the composition of the present invention 1HD and 68.9% in the composition of the present invention 10HD according to the dose of the composition of the present invention compared to the 5-FU alone treatment group. Recovery was shown, showing a tendency to recover leukocyte levels according to the concentration of the composition of the present invention (Fig. 4a, Table 4-1).

The erythrocyte (RBC) levels were not found to be different when compared with the 5-FU alone treatment group (FIG. 4B, Table 4-2).

From the above results, it can be seen that the composition of the present invention has a tendency to significantly recover platelets and leukocytes in hematopoietic toxicity following 5-FU administration.

TABLE 3

Group Control FU FU + 1KH FU + 10KH PLT (10 ⁶ / mm ³ ) 87.25 ± 19.35 ^a 52.25 ± 6.95 ^b 59.50 ± 8.58 ^ac 74.50 ± 1.91 ^ac

Table 4-1

Group Control FU FU + 1KH FU + 10KH WBC (10 ³ / mm ³ ) 3.47 ± 0.64 ^a 1.68 ± 0.86 ^b 2.54 ± 1.06 ^ab 2.83 ± 1.30 ^ab

Table 4-2

Group Control FU FU + 1KH FU + 10KH RBC (10 ³ / mm ³ ) 8.99 ± 0.39 ^a 7.69 ± 0.25 ^b 7.84 ± 0.43 ^b 8.06 ± 0.26 ^b

5-4. Effect of the composition of the present invention on weight loss by 5-FU

Following 5-FU treatment, body weight did not show statistically significant changes due to differences between individuals and the composition of the present invention did not show any significant changes. The results are published in Table 5 and FIG. 5.

Table 5

Group Control FU FU + 1KH FU + 5KH body weight (g) 19.76 ± 0.36 ^a 20.53 ± 1.10 ^a 20.80 ± 0.79 ^a 20.46 ± 0.46 ^a

5-5. Observation of changes in expression of IL2 and IFN-γ following administration of the composition of the present invention

In order to examine the effect of the immunotoxic inhibitory effect of the composition of the present invention on gene expression, RT-expression changes of IL2 (Interleukin-2) and IFN-γ (Interferon-γ), which are known as the main immunomodulators (Cytokine), were investigated. Observation was made using the PCR method. Β-actin gene was used as internal control.

The expression of IL-2 and IFN-γ genes was reduced to 50.0% or less in the 5-FU-treated group than the 5-FU-treated group, and 5-FU was lower than that of the IL-2 and IFN-γ genes. It was observed that attenuated expression reduces immunity.

In order to examine the immunosuppressive effect of the composition of the present invention, the spleen was extracted from the groups treated with each concentration, and then the recovery of IL-2 and IFN-γ gene expression was observed. As a result, IL-2 was clearly recovered upon administration of the composition of the present invention (FIGS. 6, 7). Expression of IFN-γ also showed a tendency to recover with increasing dose of the composition of the present invention (FIGS. 8, 9).

5-6. Changes in IL-2 mRNA Expression Sites through In Situ Hybridization

IL-2 is a major immunomodulator that is involved in the regulation and expression of lymphocytes responsible for immunity, and is a molecule that mediates communication between white blood cells. In this study, IL-2 mRNA expression in mouse spleen tissue using In situ hybridization method was evaluated to reduce the immune activity due to the decrease of IL-2 expression according to the anticancer treatment and to recover the composition by the composition of the present invention. We looked through the aspects. As a result, as shown in Figure 10, 5-FU and 10 HD in the composition combination treatment group of the present invention compared to the 5-FU treatment group, it was confirmed that the IL-2 mRNA expression amount is increased rapidly.

Example 2 Determination of Efficacy of Inhibition of Radiotherapy Side Effects

The clinical efficacy of the herbal combination prescription (hereinafter, referred to as KH) of Example 1 was evaluated for cancer patients undergoing radiation therapy at a medical school affiliated hospital. Radiation alone and radiation-KH combination therapy groups were compared to compare radiation completion rates and hematopoietic function.

The subjects were radiotherapy patients with a performance score (WHO standard) of 70 or less before radiation therapy and 20 or more radiation therapy groups, and consisted of 10 radiotherapy group and 10 radiation-KH combination therapy groups.

Table 6. Composition of Target Patients

Target Radiation alone treatment group Radiation-KH combination therapy group personnel 20 10 10 Male Female 15: 5 8: 2 7: 3 Age distribution 50 spaces 3 2 One 60 spaces 9 4 5 More than 70 8 4 4 Cancer type Rectal cancer 3 3 Lung cancer 2 3 Metastatic cancer 3 One Brain cancer One One Esophageal Cancer One cutaneous cancer One Blood cancer One

Radiation therapy was based on 4 weeks and was performed 5 times a week. The radiation dose was determined individually considering the characteristics of each patient and the distribution was similar in each experimental group.

Table 7. Total Radiation Dose Distribution

Experimental group Radiation alone treatment group Radiation-KH combination therapy group Total radiation dose (cGy) median 5040 5040 Value 5400 5940 Minimum value 3860 5000

4.5 g of KH produced by the method of Example 1 were sealed and packaged for one week. Each subject was asked to take a total of four bags (18 g) a day after breakfast, lunch and dinner and once before bedtime.

1. Impact on completion rate of radiation therapy

Treatment was not completed after 5 days of treatment, and leukopenia was determined when the leukocyte count decreased by more than 10%.

The experimental results are published in Table 8 and FIG. The completion rate of radiation alone treatment group was 40%, whereas the completion rate of radiation-KH combination therapy group was 80%.

Table 8. Comparison of treatment completion rate between radiotherapy alone and radiation therapy with KH

Experimental group Radiation alone treatment group Radiation-KH combination therapy group Radiation completion rate 40% 80%

2. Effect on hematopoietic function

Leukocytes and platelets were analyzed in the blood of the radiotherapy group and the radiation-KH combination group for 4 weeks.

2-1. Effect on white blood cells

Serum leukocyte levels in the radiation alone group decreased from the initial 5240 cells / uL to 3900 cells / uL after 4 weeks of treatment. In the radiation-KH combination group, the initial leukocyte count was 5250 cells / uL and the leukocyte count after 4 weeks was 4680 cells / uL. The radiation-KH group showed a marked increase in leukocyte counts after 3 and 4 weeks compared to the radiotherapy group. As a result of statistical analysis, at 3 weeks and 4 weeks, p value is 0.077 and 0.083, respectively, which is slightly larger than 0.05 widely used as a general standard, but smaller than 0.1, which is statistically significant. In addition, when the number of samples (n) is small as 10 persons in each group, increasing the number of samples seems to increase the statistical significance.

The results are posted in Table 9 and FIG. 12.

Table 9

WBC (cells / uL) Radiation alone treatment group Radiation-KH combination therapy group P 1 week 5240 ± 1248 5250 ± 1037 0.985 2 weeks 4860 ± 811 5160 ± 1247 0.532 3 weeks 4200 ± 802 5100 ± 1284 0.077 4 Weeks 3900 ± 989 4680 ± 939 0.083

2-2. Effect on Platelets

Serum leukocyte levels in the radiation alone group decreased slightly from the original 232700 cells / uL to 200700 cells / uL after 4 weeks of treatment. In the radiation-KH combination group, the initial leukocyte count was 246700 cells / uL and the leukemia level after 4 weeks was 196000 cells / uL, which was not significantly different from the radiotherapy group. As a result of statistical analysis, the p value was more than 0.7 in all treatment periods. The results suggest that the main target of hematopoietic toxicity by radiation is leukocytes rather than platelets, and that KH has a protective effect on leukocytes rather than platelets. The results are posted in Table 10 and FIG. 13.

Table 10

WBC (cells / uL) Radiation alone treatment group Radiation-KH combination therapy group P 1 week 232700 ± 94937 246700 ± 18898 0.774 2 weeks 232400 ± 80804 218800 ± 102809 0.746 3 weeks 189200 ± 56215 190100 ± 70905 0.975 4 Weeks 200700 ± 60101 196000 ± 74184 0.878

2-3. Leukopenia

Because KH showed strong leukocyte recovery, we compared the incidence of leukopenia during the treatment period. The results are published in Table 11 and FIG. 14 below. In 4 weeks of treatment, leukopenia developed in 40% of the radiation alone group, but only 20% in the radiation-KH combination group reduced the incidence rate by half.

Table 11

Period experiment group 1 week 2 weeks 3 weeks 4 Weeks Radiation alone treatment group 0 % 30% 40% 40% Radiation-KH combination therapy group 0 % 10% 10% 20%

As confirmed in the above embodiment, in hematopoietic toxicity after 5-Fluorouracil (FU) treatment, it was confirmed that the platelet level significantly increased with the concentration of the herbal composition of the present invention. There was a tendency to increase with the dose e of the composition of the present invention. The immunopotentiating effects of IL2 and IFN-γ expression levels were restored to almost normal levels at 1HD KH for IL2 and IFN-γ expression was restored to 92% at 10HD. The mRNA expression level of IL2 in the spleen determined through in situ hybridization also showed a marked increase in the expression level when the composition of the present invention was treated in combination. On the other hand, the anti-cancer effect showed the same effect in the combination treatment of the composition of the present invention in various doses compared with the 5-FU treatment alone. In view of these results, the composition of the present invention is useful for selectively suppressing side effects of the hematopoietic system while maintaining the anticancer efficacy of 5-FU.

In addition, when the combination of the composition of the present invention in combination with the radiation therapy patients, it was observed that the completion rate of radiation therapy was increased by 2 times and the incidence of leukopenia decreased by 50%.

Claims (3)

Sulfur yellow 7-20 parts by weight, Angelica 5-15 parts by weight, Cheongung 5-15 parts by weight, Baekjak 5-15 parts by weight, Cornus 3-10 parts by weight, Bark skin 1.5-5 parts by weight, wolfberry 1.5-5 parts by weight An anticancer drug side effect inhibitor, characterized in that consisting of parts, 0.5-2.0 parts by weight of safflower, and 1-3 parts by weight of licorice. The inhibitor of claim 1, wherein the anticancer agent is 5-fluorouracil. Sulfur yellow 7-20 parts by weight, Angelica 5-15 parts by weight, Cheongung 5-15 parts by weight, Baekjak 5-15 parts by weight, Cornus 3-10 parts by weight, Bark skin 1.5-5 parts by weight, wolfberry 1.5-5 parts by weight Radiation treatment side effect inhibitor, characterized in that consisting of parts, 0.5-2.0 parts by weight of safflower, and 1-3 parts by weight licorice.