Anti-nuclear radiation pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention discloses an anti-nuclear radiation ionizing radiation protection pharmaceutical composition, a preparation method thereof and an application of the anti-nuclear radiation ionizing radiation protection pharmaceutical composition in preparation of drugs for treating or preventing ionizing radiation damage represented by nuclear radiation. The invention particularly relates to an application in preparation of drugs for preventing / treating radioactive bone marrow injury caused by ionizing radiation represented by nuclear radiation. The composition disclosed by the invention has a protection effect on natural ionizing radiation and artificial radiation, can be used as a medicine for preventing life body injury caused by radioactive substance radiation, space ionizing radiation and tumor radiotherapy, and is expected to solve the current situation that radiation prevention / treatment medicines are in shortage and have general toxicity.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and relates to an ionizing radiation protection pharmaceutical composition represented by an anti-nuclear radiation, a preparation method thereof, and application of the ionizing radiation protection pharmaceutical composition in preparation of a medicine for treating or preventing ionizing radiation damage represented by nuclear radiation, in particular, in preparation of a medicine for preventing / treating radioactive myeloid damage caused by ionizing radiation represented by nuclear radiation. BACKGROUND

[0002] The following background description related to the present application is used to help the understanding of the present application, but should not be considered as prior art of the present application. All cited publications are referred in their entirety.

[0003] In daily life, radiation is everywhere and can be divided into non-ionizing radiation and ionizing radiation. Non-ionizing radiation refers to radiation with relatively low energy and cannot cause ionization of matter atoms or molecules. Non-ionizing radiation includes low-energy electromagnetic radiation, such as ultraviolet rays, light rays, infrared rays, microwaves, and radio waves. They have low energy and only make the particles in the material vibrate and the temperature rise.

[0004] Ionizing radiation, such as nuclear radiation, has higher energy than non-ionizing radiation and has a greater impact on the human body. Ionizing radiation includes natural ionizing radiation and artificial ionizing radiation. Natural ionizing radiation includes cosmic rays, naturally occurring radionuclides on earth, radon decay products in the air, and various naturally occurring radionuclides; artificial radiation includes medical diagnostic X-rays, industrial gamma rays, 60 Co-rays, heavy ion radiation, and radiation in tumor radiotherapy treatment.

[0005] At present, there are very limited drugs that can be applied to the treatment of ionizing radiation damage. There are only about 11 ionizing radiation (nuclear radiation) prevention / treatment drugs on the market worldwide. The radiation protection agents that have been marketed include amifostine, palifosine, sargramostim, prussian blue capsules, and potassium iodide. These protection agents mainly play a role in resisting damage to the healthy body caused by radiation, repairing damaged cells, and scavenging reactive oxygen radicals (ROS). However, these chemically synthesized radiation protection agents all have certain toxic side effects, can cause nausea, vomiting, diarrhea, hypotension, and adverse symptoms such as nephrotoxicity and neurotoxicity, cannot be taken for a long time, and have the disadvantages of limited administration route, short administration window period, and high cost. Therefore, drugs with small toxic side effects and good radiation protection effect are highly concerned.

[0006] Ligustrum lucidum Ait. The dried mature fruit of Ligustrum lucidum Ait. Ligustrum lucidum Ait. is steamed or stewed with wine to become Ligustrum lucidum Ait. after, its "shape like Ligustrum lucidum Ait., surface black brown or gray black, often attached with white powder frost, slightly wine aroma". Oval, elliptical or kidney-shaped. Surface black purple or gray black, wrinkled uneven, base has fruit peduncle mark or has calyx and short stem. Light in body. Outer pericarp is thin, mesocarp is relatively soft, and is easy to peel, endocarp is woody, yellowish brown, has longitudinal ridge, and usually has 1 seed after breaking, kidney-shaped, purple black, oily. Slightly wine aroma, sweet, bitter and astringent taste. The Ligustrum lucidum Ait. used in the application can also use Ligustrum lucidum Ait.

[0007] Eclipta prostrata L. is the dried aboveground part of Eclipta prostrata L. of the Compositae, an annual herb, the whole body is covered with white hair. The decoction piece is irregular small section, the stem is cylindrical, has longitudinal ridge, the diameter is 2-5mm, the section is white pith or hollow after cutting, the surface is greenish brown or dark green. The leaves are opposite, nearly unattached, the leaf blade is wrinkled and curled or broken, the complete one is long lanceolate, entire or with shallow teeth, dark green. The achenes are oval and flat, 2-3mm long, brown or light brown. Slight smell, slightly salty taste.

[0008] Lycium barbarum L. is the dried mature fruit of Lycium barbarum L. of the Solanaceae. It is spindle-shaped or elliptical, 6-20mm long, and 3-10mm in diameter. The surface is red or dark red, with a small protruding stigma mark at the top and a white fruit stalk mark at the base. The fruit skin is flexible and wrinkled; the fruit flesh is fleshy and soft.

[0009] Cistanche deserticola Y.C.Ma or Cistanche tubulosa (Schenk) Wight, the dried succulent stem with scale leaves. It is flat cylindrical, slightly curved, 3-15cm long, and 2-8cm in diameter. The surface is brownish or grayish brown, covered with succulent scale leaves arranged in a tile-like pattern, usually with broken scale leaf tips. Heavy in body, hard and slightly flexible, not easy to break, brownish in cross section, with light brown dot-shaped vascular bundles arranged in a wavy ring. Slight smell, sweet and slightly bitter taste. 20-50 seeds, kidney-shaped, flat and curved, 1.5-1.9mm long, 1-1.7mm wide, light yellow or brownish yellow in color. Slight smell, sweet taste. SUMMARY

[0010] In view of the fact that there are very limited drugs for preventing and treating ionizing radiation damage, the present application starts from traditional plants with a long history of drug use, and is scientifically matched and carefully combined on the basis of conforming to the basic theory of traditional Chinese medicine.

[0011] This invention discloses a novel composition, its preparation process, and its application in the preparation of drugs for treating / preventing radiation damage, particularly in the treatment of ionizing radiation damage.

[0012] The composition of this invention is prepared from the following raw materials: Ligustrum lucidum, Eclipta prostrata, Lycium barbarum, and Cistanche deserticola, in the following weight ratios:

[0013] 10-20g of privet fruit

[0014] Eclipta prostrata 5-15g

[0015] 10-20g of goji berries

[0016] Cistanche deserticola 1-10g.

[0017] The composition of the present invention is further preferably prepared from the following raw materials:

[0018] 15g of privet fruit

[0019] 10g of Eclipta prostrata

[0020] 15g of goji berries

[0021] 5g of Cistanche deserticola.

[0022] The compositions of the present invention can be extracted with water or with ethanol, including extraction with 0-95% ethanol.

[0023] Further extraction can be performed using a 30-80% ethanol solution;

[0024] Further extraction can be performed using a 40-70% ethanol solution;

[0025] Further extraction can be performed using a 55-65% ethanol solution, preferably a 60% ethanol solution.

[0026] Example of extraction method for the composition of the present invention:

[0027] Pre-treat the compound medicinal materials. Use a high-speed universal grinder to slightly break the hard outer shell of the privet fruit. Cut the processed cistanche into 1cm pieces.

[0028] Weigh out 5 times the normal dosage of the compound medicine, mix the compound medicinal materials, place them in a round-bottom flask, add 10 times the amount of water, heat under reflux for 1.5 hours, take out the filtrate, add 8 times the amount of water, heat under reflux for 1.5 hours, combine the two filtrates to obtain 3500 mL, concentrate to obtain an extract, place the extract in a tray and put it in a 60℃ oven to dry to block shape, pulverize to obtain a total of 105 g of powder.

[0029] The ionizing radiation described in this application includes natural ionizing radiation and artificial radiation. Its types include, but are not limited to, X-ray irradiation, gamma-ray irradiation, heavy ion irradiation, and alpha-ray irradiation. 60 Co rays, 136 Cs、 192 Ir radiation and other types of radiation. Specific scenarios include: radiation protection and treatment drugs for radiation damage to the body during tumor radiotherapy and chemotherapy, and in the event of nuclear material leakage.

[0030] The compositions of this invention can be used in the preparation of drugs for the prevention / treatment of ionizing radiation; in particular, the compositions of this invention can also be used in the preparation of drugs for the prevention / treatment of radiation-induced hematopoietic system damage, radiation-induced bone marrow damage, radiation-induced intestinal damage, DNA damage caused by ionizing radiation, and as adjuvant drugs for tumor radiotherapy. Tumors include, but are not limited to, intestinal tumors, hematopoietic system tumors, and myeloma.

[0031] This invention provides a novel radiation injury treatment / protection drug that can alleviate the current situation of severe shortage of radiation prevention / treatment drugs. Attached Figure Description

[0032] Figure 1 A schematic diagram illustrating gamma-ray-induced radiation damage to the hematopoietic system in mice and drug administration.

[0033] Figure 2 Changes in body weight in mice after whole-body irradiation with 4 Gy;

[0034] Figure 3 Changes in peripheral blood cells in 4Gy TBI mice, including: (a) white blood cells; (b) percentage of lymphocytes; (c) percentage of neutrophils; (d) platelets; (e) red blood cells; and (f) hemoglobin.

[0035] Figure 4 Damage to bone marrow cells in the femur of mice after radiation;

[0036] Figure 5 The effect of each group on the decrease of thymus index in mice is shown in the figure: (a) thymus representative graph; (b) thymus index.

[0037] Figure 6 The effect of each group on the reduction of spleen index in mice is shown in the figure: (a) representative spleen graph; (b) spleen index.

[0038] In each figure, C represents the blank control group, M represents the irradiation model group, water extract represents the irradiation + water extract group, 60% ethanol extract represents the irradiation + 60% ethanol extract group, 80% ethanol extract represents the irradiation + 80% ethanol extract group, Shengxuebao represents the irradiation + Shengxuebao group, and Tremella represents the irradiation + Tremella spore sugar group. Detailed Implementation

[0039] The present invention will be further described below with reference to the accompanying drawings and embodiments:

[0040] The experimental animals were SPF-grade male C57BL / 6 mice, weighing 20–22 g, purchased from Beijing Huafukang Biotechnology Co., Ltd. The mice were housed in the SPF-grade experimental animal center of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences, with a temperature controlled at 22±3℃, relative humidity controlled at 40%–60%, and light and dark alternating every 12 hours. All animal experiments were reviewed and approved by the Animal Ethics Committee of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences.

[0041] Irradiation source: 137 Csγ irradiation source, provided by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences;

[0042] Lycium barbarum extract:

[0043] Ligustrum lucidum, Anguo City Tongyi Traditional Chinese Medicine Pieces Co., Ltd.

[0044] Mohanlian Anguo City Tongyi Traditional Chinese Medicine Pieces Co., Ltd.

[0045] Goji Berry Hebei Renxin Pharmaceutical Co., Ltd.

[0046] Cistanche deserticola Tianjin Tongyi Traditional Chinese Medicine Pieces Technology Development Co., Ltd.

[0047] Shengxuebao Mixture, Tsinghua Deren Xi'an Xingfu Pharmaceutical Co., Ltd.

[0048] Tremella fuciformis capsules Jilin Shuangyao Pharmaceutical Group Co., Ltd.

[0049] Other reagents: commercially available;

[0050] Instruments: Flow cytometer, fully automated blood analyzer, enzyme-linked immunosorbent assay (ELISA) reader, cell counter, centrifuge, clean bench, etc.

[0051] This invention screens the extraction process of the Lycium barbarum whitening composition using three different methods. First, based on bioinformatics big data network pharmacology, it makes a simple prediction of the important active ingredients in the Lycium barbarum whitening composition that resist radiation damage to the hematopoietic system. Then, combined with the pharmaceutical experimental results of the three different extraction processes, and based on the content of characteristic components of medicinal materials in the samples obtained by the three different extraction processes and the active ingredients predicted by network pharmacology, the index components of the Lycium barbarum whitening composition are preliminarily determined. Finally, combined with the pharmacodynamic experimental results of the three different extraction processes, the extraction process of the Lycium barbarum whitening composition is determined.

[0052] Based on network pharmacology predictions and the main active ingredients detected, it was preliminarily determined that rhodioloside, echinacoside, ligustrazine, and betaine can be used as content determination indicators for the Lycium barbarum-based whitening composition to evaluate the extraction process.

[0053] Example 1: Preparation of the Lycium barbarum and Ligusticum striatum extract (water extraction)

[0054] The prescription for medicinal materials, by weight, is as follows: 15g of Ligustrum lucidum; 10g of Eclipta prostrata; 15g of Lycium barbarum; and 5g of Cistanche deserticola.

[0055] Pre-treat the compound medicinal materials. Use a high-speed universal grinder to slightly break the hard outer shell of the privet fruit. Cut the processed cistanche into 1cm pieces.

[0056] Weigh out 5 times the normal dosage of the compound medicine, mix the compound medicinal materials, place them in a round-bottom flask, add 10 times the amount of water, heat under reflux for 1.5 hours, take out the filtrate, add 8 times the amount of water, heat under reflux for 1.5 hours, combine the two filtrates to obtain 3500 mL, concentrate to obtain an extract, place the extract in a tray and put it in a 60℃ oven to dry to block shape, pulverize to obtain a total of 105 g of powder.

[0057] 10-20g of privet fruit

[0058] Eclipta prostrata 5-15g

[0059] 10-20g of goji berries

[0060] Cistanche deserticola 1-10g.

[0061] Example 2: Preparation of the Lycium barbarum and Ligusticum striatum extract (water extraction)

[0062] The prescription for medicinal materials, by weight, is as follows: 10g of Ligustrum lucidum; 15g of Eclipta prostrata; 10g of Lycium barbarum; and 10g of Cistanche deserticola.

[0063] Pre-treat the compound medicinal materials. Use a high-speed universal grinder to slightly break the hard outer shell of the privet fruit. Cut the processed cistanche into 1cm pieces.

[0064] Weigh out 5 times the normal dosage of the compound medicine, mix the compound medicinal materials, place them in a round-bottom flask, add 10 times the amount of water, heat under reflux for 1.5 hours, take out the filtrate, add 8 times the amount of water, heat under reflux for 1.5 hours, combine the two filtrates to obtain 3500 mL, concentrate to obtain an extract, place the extract in a tray and put it in a 60℃ oven to dry to block shape, pulverize to obtain a total of 108 g of powder.

[0065] Example 3: Preparation of the extract of the Lycium barbarum and Ligusticum striatum combination (water extraction)

[0066] The prescription for medicinal materials, by weight, is as follows: 20g of Ligustrum lucidum; 5g of Eclipta prostrata; 20g of Lycium barbarum; and 1g of Cistanche deserticola.

[0067] Pre-treat the compound medicinal materials. Use a high-speed universal grinder to slightly break the hard outer shell of the privet fruit. Cut the processed cistanche into 1cm pieces.

[0068] Weigh out 5 times the normal dosage of the compound medicine, mix the compound medicinal materials, place them in a round-bottom flask, add 10 times the amount of water, heat under reflux for 1.5 hours, take out the filtrate, add 8 times the amount of water, heat under reflux for 1.5 hours, combine the two filtrates to obtain 3500 mL, concentrate to obtain an extract, place the extract in a tray and put it in a 60℃ oven to dry to block shape, pulverize to obtain a total of 101 g of powder.

[0069] Example 4: Preparation of the extract of the Lycium barbarum and Ligusticum striatum combination (60% ethanol extraction)

[0070] The dosage of the medicinal materials was the same as in Example 1. The compound medicinal materials were pre-treated. The hard outer shell of the privet fruit was slightly broken using a high-speed universal pulverizer. The processed cistanche was cut into 1cm pieces. The medicinal materials were weighed and mixed at 5 times the normal dosage of the compound, placed in a round-bottom flask, and 10 times the amount of 60% ethanol was added. The mixture was heated under reflux for 1.5 hours, and the filtrate was collected. Then, 8 times the amount of 60% ethanol was added, and the mixture was heated under reflux for 1.5 hours. The two filtrates were combined to obtain 3600mL, which was concentrated to obtain an extract. The extract was placed on a tray and dried in a 60℃ oven until it formed blocks. The blocks were then pulverized to obtain a total powder of 96.5g.

[0071] Example 5: Preparation of the extract of the Lycium barbarum and Ligusticum striatum combination (80% ethanol extraction)

[0072] The dosage of the medicinal materials was the same as in Example 1. The compound medicinal materials were pre-treated. The hard outer shell of the privet fruit was slightly broken using a high-speed universal pulverizer. The processed cistanche was cut into 1cm pieces. The medicinal materials were weighed and mixed at 5 times the normal dosage of the compound, placed in a round-bottom flask, and 10 times the amount of 80% ethanol was added. The mixture was heated under reflux for 1.5 hours, and the filtrate was collected. Then, 8 times the amount of water was added, and the mixture was heated under reflux for 1.5 hours. The two filtrates were combined to obtain 3400mL, which was concentrated to obtain an extract. The extract was placed on a tray and dried in a 60℃ oven until it formed blocks. The blocks were then pulverized to obtain a total powder of 97.5g.

[0073] Example 6: Content Determination of Three Extraction Methods

[0074] HPLC Chromatographic Conditions

[0075] Chromatographic column: ZORBAX SB-Aq (4.6 × 250 mm, 5 μm); Mobile phase: Acetonitrile (A) - 0.1%

[0076] Phosphoric acid (B); Detection wavelength: 225 nm; Column temperature: 30 ℃; Flow rate: 1.0 mL / min; Injection volume: 10 μL. Elution gradient: see Table 1.

[0077] Table 1. HPLC gradient elution conditions

[0078]

[0079] Based on HPLC analysis, the contents of key components in the water-extracted, 60% ethanol-extracted, and 80% ethanol-extracted samples were calculated. The results showed that the content of rhodioloside in the water extract was lower than that in the 60% and 80% ethanol extracts, while the content of ligustrum lucidum glycoside in the water extract was twice that in the 60% and 80% ethanol extracts. Overall, the water extract had a higher content of key components, as detailed in Table 2 below.

[0080] Table 2. Determination of the content of indicative components in the test samples from three extraction processes.

[0081]

[0082] Example 7: Pharmacodynamic Experiments with Different Extraction Processes

[0083] Drug preparation. Water-extracted drug powder, 60% ethanol-extracted drug powder (Example 4), and 80% ethanol-water-extracted drug powder (Example 5) were each prepared with purified water to form solutions with a crude drug concentration of 0.375 g / mL. The positive drug Shengxuebao mixture was prepared with purified water to a concentration of 645 μL / mL. The positive drug Tremella fuciformis capsule powder was extracted and prepared with 0.5% sodium carboxymethyl cellulose to form a concentration of 42.9 mg / mL.

[0084] Experimental animal grouping. Seventy purchased C57BL / 6 mice were acclimatized in an SPF-grade animal facility for one week and then randomly divided into seven groups using a block randomization method: blank control group, irradiation model group, irradiation + water extraction group (20 mL / kg), irradiation + 60% ethanol extraction group (20 mL / kg), irradiation + 80% ethanol extraction group (20 mL / kg), irradiation + Shengxuebao group (10 mL / kg), and irradiation + Tremella fuciformis spore sugar group (10 mL / kg), with ten mice in each group.

[0085] Administration and irradiation methods for mice. The blank control group and irradiation model group were given 0.5% sodium carboxymethyl cellulose; the irradiation + water extract group, irradiation + 60% ethanol extract group, and irradiation + 80% ethanol extract group were given the corresponding concentrations of the drug solution, 0.4 mL orally each time; the irradiation + Shengxuebao group and irradiation + Tremella fuciformis group were given the corresponding concentrations of the drug solution, 0.2 mL orally each time. Gavage was administered for 7 consecutive days before irradiation and for 6 consecutive days after irradiation. Irradiation was performed 0.5 hours after drug administration on the day of irradiation, requiring a single systemic 4 Gy dose. 137 Mice were irradiated with Csγ rays at a dose rate of 0.99 Gy / min. They were then sacrificed on day 7 post-irradiation for subsequent testing. Figure 1This is a schematic diagram illustrating gamma-ray-induced radiation damage to the hematopoietic system in mice and drug administration.

[0086] Graphpad Prism 8.0.1 software was used for graph analysis, and SPSS 26.0 statistical software was used for intergroup comparisons. Student's t test was used for statistical analysis. Statistical results are expressed as Mean ± SD, where P < 0.05 indicates a significant difference.

[0087] Example 8: Effect of the Lycium barbarum and Ligusticum striatum composition on the body weight of mice after 4 Gy whole-body irradiation

[0088] Following the methods and samples in Example 7, the body weight changes of mice in each group were recorded daily during the experiment. Results are shown below. Figure 2 .

[0089] like Figure 2 As shown, experimental mice were administered water extract, 60% ethanol extract, 80% ethanol extract, Shengxuebao (a traditional Chinese medicine), and Tremella fuciformis via gavage for 7 consecutive days. There was no significant difference in weight gain compared to the blank control group. The mice maintained a stable weight gain. The experimental mice received a single 4Gy dose of the drug. 137 Following Csγ-ray irradiation, each group continued to be administered drugs via gavage, including water extract, 60% ethanol extract, 80% ethanol extract, Shengxuebao (a traditional Chinese medicine), and Tremella fuciformis. Compared with the blank control group, the body weight of mice in the irradiation group and each irradiation plus drug group showed a trend of initial decrease followed by slow increase. On day 6 after irradiation, the body weight of the irradiation group reached its lowest value on day 7. The body weight of mice in the water extract group, 60% ethanol extract group, 80% ethanol extract group, Shengxuebao group, and Tremella fuciformis group also reached their lowest values. The body weight of the water extract group was better than that of the other drug groups from day 4 to day 7 after irradiation. During the period from irradiation until the mice were sacrificed for tissue collection, there was no significant difference in body weight between the mice in the simple irradiation group and the mice in the irradiation plus drug groups. Among the irradiation plus drug groups, the body weight of mice in the water extract group was slightly better than that of the other drug groups, but the difference was not statistically significant.

[0090] Example 9: Effects of the Lycium barbarum and Ligusticum striatum composition on peripheral blood routine tests in mice irradiated with 4 Gy whole body

[0091] According to the method and samples in Example 5, on the seventh day after irradiation, the mice were weighed, and the whiskers on one side were trimmed. Then, using ophthalmic forceps, blood was collected from the mice by enucleation into a pre-labeled 1.5 mL EP tube containing an anticoagulant (dipotassium ethylenediaminetetraacetate, EDTA-K2). The EP tube was gently shaken to ensure sufficient contact between the anticoagulant and the blood. The peripheral blood routine changes of each group of experimental mice were analyzed using the mouse whole blood mode of a fully automated blood analyzer. The results are shown below. Figure 3 (a, b, c, d, e, f).

[0092] likeFigure 3 As shown, a and b represent the changes in WBC count, lymphocyte percentage (Lymph%), neutrophil percentage (Gran%), and platelet (PLT) count in mouse peripheral blood, respectively. The results indicate that compared to the control group, the irradiation-only group showed changes in peripheral blood parameters, including decreased or increased levels of white blood cells and neutrophils, which are detrimental to mouse health, suggesting that whole-body irradiation causes damage to the peripheral blood of mice. Compared to the irradiation-only group, the drug-treated groups significantly improved peripheral blood parameters, such as increasing white blood cell and lymphocyte percentages and platelet counts, and decreasing neutrophil counts. While the water extract group was not as effective as the 80% ethanol extract group in increasing platelet count, it was superior to other drug-treated groups in improving white blood cell and lymphocyte percentages and alleviating the increase in neutrophils.

[0093] Figures e and f show the changes in peripheral blood erythrocyte and hemoglobin levels in mice, respectively. The results indicate that irradiation led to a decrease in erythrocyte and hemoglobin levels in the experimental mice, with the water extract group also showing an improving effect. These results suggest that none of the drug-treated groups had significant toxic side effects on the peripheral blood counts of normal mice, and that they provided some protection against radiation-induced hematopoietic damage in C57BL / 6 mice, with the water extract group showing the best effect. (Statistical analysis: Compared with the irradiation-only group, *P<0.05, ****P<0.0001, n=10.)

[0094] Example 10: Effects of the Lycium barbarum and Ligusticum striatum formula on nucleated femoral cells in mice irradiated with 4 Gy whole body.

[0095] According to the method and sample in Example 7, after the mice were euthanized by cervical dislocation, their right hip and leg area was moistened with alcohol, the skin was carefully cut open and the femur was removed. After carefully cleaning the residual muscle tissue attached to the outside of the femur, the bloodstains on the outside were simply rinsed with PBS.

[0096] Using a 1mL syringe, after removing the outer packaging, draw 1mL of pre-cooled PBS solution and carefully insert it into the femoral head side. Rinse the bone marrow repeatedly until the femur becomes transparent. Place the rinsed bone marrow suspension in a pre-labeled 1.5mL EP tube and place it on ice for later use. Use a 1mL pipette to aspirate the rinsed bone marrow suspension and filter it through a 70μM filter into another new EP tube to form a single-cell bone marrow suspension. Label the suspension. All of the above processes are performed on ice. (4) Store the filtered bone marrow cells on ice. Use the mouse whole blood mode of an automated blood analyzer to analyze and count the number of bone narrow nucleated cells (BMNC) in each group of experimental mice. Shake the EP tube thoroughly before measurement to ensure the cell suspension is homogeneous. The results of the number of nucleated cells in the mouse femur are shown in the figure. Figure 4 .

[0097] Depend on Figure 4 The results showed that compared with the blank control group, the BMNC content of irradiated mice was significantly decreased in the irradiation-only group. Compared with the irradiation-only group, the BMNC content of irradiated mice in the water extraction group was significantly increased, while the BMNC content in the 60% ethanol extraction group and the 80% ethanol extraction group decreased. Among them, the 80% ethanol extraction group showed more significant damage to the BMNCs of irradiated mice. These results demonstrate that the water extraction group is non-toxic to nucleated femoral cells in mice and can improve irradiation-induced damage to mouse bone marrow cells. (Statistical analysis: Compared with the irradiation-only group, *P<0.05, ****P<0.0001, n=10.)

[0098] Example 11 Effect of the Lycium barbarum and Ligusticum striatum composition on the organ indices of spleen and thymus in mice irradiated with 4 Gy whole body

[0099] According to the method and sample of Example 7, when collecting samples, radiation-sensitive organs such as the spleen and thymus of each group of mice were removed, and the bloodstains on the surface were rinsed off with physiological saline. After drying, they were accurately weighed on a balance with a weight of 0.1% and the weight was recorded.

[0100] The changes in organ indices of major organs among the mice in each group were calculated and analyzed using the following formula:

[0101] Organ index = organ weight (mg) / animal body weight (g, where animal body weight is the mouse's weight on the day of dissection)

[0102] Images of the spleen and thymus of mice were taken. On day 7 post-irradiation, mice were euthanized by cervical dislocation, and the spleen and thymus were dissected, weighed, and photographed. Thymus and thymus index data for each group of mice are shown below. Figure 5 Spleen and spleen index are seen Figure 6 .

[0103] Depend on Figure 5 and Figure 6 It was found that, compared with the blank control group, irradiation could reduce the size of the spleen and thymus in mice. Compared with the irradiation group, some drug-treated groups could increase the thymus and spleen indices of irradiated mice. Among them, the water extract group had the most significant effect on increasing the thymus and also had a significant effect on increasing the spleen organ index. The 80% ethanol extract group and the Shengxuebao group both reduced the two organ indices. The water extract group was better than other groups in increasing the thymus and spleen organ indices, suggesting that the drug is basically non-toxic to the organs of irradiated mice and can alleviate the reduction of organ indices such as thymus and spleen induced by irradiation in mice.

[0104] In summary, this invention provides a naturally derived, safe, and effective anti-ionizing radiation drug composition, which is expected to address the current situation where radiation prevention / treatment drugs have varying degrees of toxicity and are in short supply in clinical practice.

Claims

1. A pharmaceutical composition prepared from the following raw materials: Ligustrum lucidum, Eclipta prostrata, Lycium barbarum, and Cistanche deserticola.

2. The pharmaceutical composition according to claim 1, wherein the weight ratio is as follows:

3. The pharmaceutical composition according to claim 2, wherein the weight ratio is as follows:

4. The pharmaceutical composition according to claim 1 can be extracted using a 0-95% ethanol solution.

5. The pharmaceutical composition according to claim 4 can be extracted with a 30-80% ethanol solution; preferably a 60% ethanol solution.

6. Use of the composition according to claims 1-3 in the preparation of a drug for the prevention / treatment of ionizing radiation.

7. The application according to claim 6, characterized in that... Application of the Qizhen Shengbai composition in the preparation of drugs for the prevention / treatment of radiation-induced hematopoietic system damage caused by ionizing radiation.

8. The application according to claim 6, characterized in that... Application of the Lycium barbarum-based white blood cell-boosting composition in the preparation of drugs for the prevention / treatment of radiation-induced bone marrow damage caused by ionizing radiation.

9. The application according to claim 6, characterized in that... Application of the Qizhen Shengbai composition in the preparation of drugs for the prevention / treatment of radiation-induced intestinal injury caused by ionizing radiation.

10. The application according to claim 6, characterized in that... Application of the Lycium barbarum-based white blood cell-enhancing composition in the preparation of drugs for the prevention / treatment of DNA damage caused by ionizing radiation.

11. The application according to claim 6, characterized in that, Application in the preparation of adjuvant drugs for tumor radiotherapy.

12. The application according to claim 11, characterized in that, Tumors include intestinal tumors, hematopoietic system tumors, and myeloma.

Images