Application of irradiated blood product in preventing or treating leucopenia

Abstract

The invention discloses an application of an irradiated blood product in prevention or treatment of leucopenia, the blood product is irradiated by using rays with a dose of less than 300mGy, then the blood product is input back into a body to induce the body to generate an excitation effect, the rays are prevented from directly irradiating the body, and the protection effect is controlled by adjusting the irradiation dose and the blood transfusion amount. And radiation-induced leucopenia can be prevented. Compared with an existing leucopenia treatment method, the leucopenia treatment method has the advantages that the treatment convenience is improved, the cost is low, the safety is high, and a new technical means is provided for treatment of leucopenia.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine technology, and specifically relates to the application of irradiated blood products in preventing or treating leukopenia. Background Art

[0002] Ionizing radiation is widely used in tumor treatment, medical diagnosis, and industrial production, but it can also cause serious damage to the human body, of which the blood system is one of the most sensitive target organs. Radiation-induced leukopenia not only increases the risk of infection, but may also lead to treatment interruptions or radiotherapy dose adjustments for cancer patients receiving radiotherapy, affecting clinical efficacy. Therefore, how to effectively prevent and treat radiation-related blood and immune system damage, especially leukopenia, has become an important topic in the field of radiation medicine and hematology.

[0003] Leukopenia is a hematological abnormality that requires close attention. Its definition and diagnosis are mainly based on the peripheral blood white blood cell count, which refers to a persistent white blood cell count of <4.0×10 9 / L. At present, the clinical methods for preventing and treating radiotherapy-induced leukopenia mainly include the use of hematopoietic growth factors, immunomodulators and traditional Chinese medicine preparations. However, these methods are expensive, have limited effects, and have some adverse reactions. Therefore, it is of great clinical significance to explore new treatment methods and combined drug use as supplementary strategies.

[0004] In recent years, the biological effects of low-dose irradiation have attracted widespread attention from researchers. Studies have shown that low-dose irradiation can have a positive effect on the body by inducing adaptive responses, stimulating stem cell proliferation, and other mechanisms. This phenomenon is called radiation hormesis. Studies have shown that whole-body low-dose irradiation (75mGy) of mice can stimulate the proliferation of hematopoietic stem cells and progenitor cells in the mouse bone marrow and mobilize them to the peripheral blood. It can also stimulate the increase of multiple endogenous hematopoietic factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Whole-body low-dose ionizing radiation was used to treat two patients with elevated prostate-specific antigen (PSA) after prostate cancer surgery, one of whom had bone metastasis. After treatment, the PSA of both patients decreased and remained at a low level, and the bone metastasis almost completely disappeared (Kojima S, Tsukimoto M, Shimura N, et al. Treatment of cancer and inflammation with low-dose ionizing radiation: three case reports. Dose Response, 2017, 15(1): 1559325817697531.).

[0005] At present, autologous blood transfusion technology is widely used in clinical practice, and its safety and effectiveness have been confirmed (Pan JK, Hong KH, Xie H, et al. The efficacy and safety of autologous blood transfusion drainage in patients undergoing total knee arthroplasty: a meta-analysis of 16 randomized controlled trials. BMC Musculoskelet Disord, 2016, 17(1): 452.). Since autologous blood comes from one's own blood tissue, autologous blood transfusion does not require transportation, matching and testing, which significantly reduces the cost of blood transfusion and avoids errors that may be caused by corresponding operations. In addition, autologous blood transfusion can reduce the incidence of postoperative immunosuppression and improve patient prognosis.

[0006] Therefore, combining irradiation technology with autologous blood transfusion technology for the prevention and treatment of leukopenia is of great significance for improving the quality of life of patients. Summary of the invention

[0007] In order to better prevent and treat leukopenia, alleviate the pain of patients, and improve the quality of life of patients, the present invention provides the following technical solutions.

[0008] In a first aspect, the present invention provides the use of an irradiated blood product in the preparation of a product for preventing or treating leukopenia.

[0009] Preferably, the irradiated blood product is obtained after irradiation with a dose of ≤300mGy.

[0010] Furthermore, the irradiation dose of the radiation is 100 to 300 mGy, for example, 100 mGy, 110 mGy, 120 mGy, 130 mGy, 140 mGy, 150 mGy, 160 mGy, 170 mGy, 180 mGy, 190 mGy, 200 mGy, 210 mGy, 220 mGy, 230 mGy, 240 mGy, 250 mGy, 260 mGy, 270 mGy, 280 mGy, 290 mGy, and 300 mGy.

[0011] Preferably, the rays include but are not limited to cobalt 60, α rays, β rays, γ rays or X-rays, more preferably X-rays.

[0012] Preferably, the leukopenia is radiation- or drug-induced leukopenia.

[0013] Preferably, the blood product comprises whole blood or blood components, more preferably whole blood.

[0014] Furthermore, the blood sample is derived from autologous peripheral blood.

[0015] In a second aspect, the present invention provides a method for preparing a blood product, comprising the step of irradiating ex vivo peripheral blood with radiation at a dose of ≤300 mGy.

[0016] Furthermore, the irradiation dose of the radiation is 100 to 300 mGy, for example, 100 mGy, 110 mGy, 120 mGy, 130 mGy, 140 mGy, 150 mGy, 160 mGy, 170 mGy, 180 mGy, 190 mGy, 200 mGy, 210 mGy, 220 mGy, 230 mGy, 240 mGy, 250 mGy, 260 mGy, 270 mGy, 280 mGy, 290 mGy, and 300 mGy.

[0017] Preferably, the rays include but are not limited to cobalt 60, α rays, β rays, γ rays or X-rays, more preferably X-rays.

[0018] In a third aspect, the present invention provides an irradiated blood product prepared according to the method described in the second aspect.

[0019] In a fourth aspect, the present invention provides a method for preventing and treating leukopenia, wherein the method comprises the step of returning the blood product described in the third aspect to the patient.

[0020] Preferably, the input amount of the blood product is 5% to 20% of the autologous circulating blood volume, for example: 5%, 10%, 15%, 20%.

[0021] In a fifth aspect, the present invention provides use of a radiation source in preparing a device for preventing or treating leukopenia.

[0022] Preferably, the device comprises the radiation source, and the radiation dose adjustment range of the radiation generated by the radiation source is ≤300mGy.

[0023] Furthermore, the dose of the radiation generated by the radiation source can be adjusted to 100-300mGy, for example, 100mGy, 110mGy, 120mGy, 130mGy, 140mGy, 150mGy, 160mGy, 170mGy, 180mGy, 190mGy, 200mGy, 210mGy, 220mGy, 230mGy, 240mGy, 250mGy, 260mGy, 270mGy, 280mGy, 290mGy, and 300mGy.

[0024] Preferably, the rays include but are not limited to cobalt 60, α rays, β rays, γ rays or X-rays, more preferably X-rays.

[0025] Preferably, the leukopenia is radiation- or drug-induced leukopenia.

[0026] In a sixth aspect, the present invention provides a blood irradiation device for treating ex vivo blood, wherein the blood irradiation device comprises an irradiation source, and the dose adjustment range of the irradiation rays generated by the irradiation source is ≤300mGy.

[0027] Furthermore, the dose of the radiation generated by the radiation source can be adjusted to 100-300mGy, for example, 100mGy, 110mGy, 120mGy, 130mGy, 140mGy, 150mGy, 160mGy, 170mGy, 180mGy, 190mGy, 200mGy, 210mGy, 220mGy, 230mGy, 240mGy, 250mGy, 260mGy, 270mGy, 280mGy, 290mGy, and 300mGy.

[0028] Preferably, the rays include but are not limited to cobalt 60, α rays, β rays, γ rays or X-rays, more preferably X-rays.

[0029] Beneficial effects of the present invention:

[0030] 1. The present invention adopts a new method of irradiating the autologous blood drawn with a dose of less than 300mGy and then reinfusing it to induce the body to produce an excitatory effect, avoid direct irradiation of the body with radiation, control the protective effect by adjusting the irradiation dose and the amount of blood transfused, and prevent radiation-induced leukocytopenia.

[0031] 2. Compared with the existing white blood cell therapy, the treatment method of the present invention increases the convenience of treatment, has a low-cost and high-safety application prospect, and provides a new technical means for the treatment of leukopenia. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Shown are the results of white blood cell counts in rats after 1Gy X-ray irradiation;

[0033] Figure 2 The figure shows the effect of different irradiation doses and different transfusion volumes on the peripheral leukocyte count of rats. A. 100mGy, 5% and 10% transfusion volume; B. 150mGy, 5% and 10% transfusion volume; C. 200mGy, 5% and 10% transfusion volume; D. 100mGy, 150mGy, 200mGy, 10% transfusion volume;

[0034] Figure 3Shown is the change of body weight in the radiation-induced leukopenia rat model by LDIAPBR;

[0035] Figure 4 Shown are the effects of LDIAPBR on spleen index and thymus index in the radiation-induced leukopenia rat model, A. Changes in spleen index; B. Changes in thymus index;

[0036] Figure 5 The figure shows the effect of LDIAPBR on peripheral blood cells in the radiation-induced leukopenia rat model, A. white blood cell count; B. lymphocyte count; C. neutrophil count; D. red blood cell count; E. hemoglobin content; F. platelet count;

[0037] Figure 6 The results show the effect of LDIAPBR on bone marrow nucleated cells in the radiation-induced leukopenia rat model. A. Bone marrow nucleated cell count; B. Bone marrow cell viability;

[0038] Figure 7 Shown are HE staining images of bone marrow tissue in rat models;

[0039] All data in the figures are expressed as mean ± SD; n = 9 per group; *P < 0.05, ***P < 0.001. DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described below in conjunction with the embodiments and drawings, and the advantages and features of the present invention will become clearer with the description. However, it should be understood that the embodiments are only exemplary and do not limit the scope of the present invention.

[0041] Example 1 Feeding of experimental animals

[0042] 81 healthy male SPF SD rats (purchased from Beijing Weitong Lihua Co., Ltd., laboratory animal quality certificate number: SCXK (Beijing) 2016-0007) were selected, weighing (220 ± 20) g, 8-10 weeks old, and kept in a clean animal room with alternating lighting of 12h dark / 12h light, maintaining temperature at (23 ± 2) ° C and humidity at (45 ± 5)%. The rats were adaptively raised for 3 days before the experiment. The laboratory animal breeding facility certificate number is SYXK (Beijing) 2021-0067.

[0043] Example 2 Construction of leukopenia animal model

[0044] SD rats were randomly divided into a modeling group (1GyX-ray) and a normal control group, with 5 rats in each group. After 3 days of normal feeding and adaptation to the environment (d0), blood routine tests were performed. One day after the blood routine test (d1), the modeling group was irradiated with 1Gy whole-body X-rays (radiation source skin distance was 50cm, dose rate was 42mGy / min) in a conscious state, and the control group was irradiated with 0Gy (sham irradiation). The changes in the number of peripheral blood leukocytes were tested every two days.

[0045] like Figure 1 As shown in the figure, after the model group received a single 1Gy X-ray irradiation on d1, the peripheral blood white blood cell count (WBC) began to decrease, reached the lowest point on d5, and then gradually increased, and returned to the normal level before irradiation on d11. After sham irradiation (0Gy) on d1 in the control group, WBC always fluctuated slightly within the normal range. This shows that the radiation injury animal model was successfully established.

[0046] Example 3 Screening of autologous peripheral blood external irradiation dose and blood transfusion volume

[0047] SD rats were randomly divided into 100mGy×5% group, 100mGy×10% group, 150mGy×5% group, 150mGy×10% group, 200mGy×5% group, 200mGy×10% group and control group. After 3 days of normal feeding and adaptation to the environment, blood routine was tested, and the time was set as d0. One day after the blood routine test (d1), 5% of the rat circulating blood volume (rat circulating blood volume ≈ 64mL / kg×rat weight) was drawn from the femoral artery of the 100mGy×5% group, 150mGy×5% group and 200mGy×5% group into a citrate anticoagulant tube, and the puncture site was pressed with a cotton ball, and the indwelling needle was withdrawn. The blood in the anticoagulation tube was irradiated at 100, 150 and 200 mGy irradiation doses (radiation source skin distance was 50 cm, irradiation chamber size was 43.2×43.2×38 cm, dose rate was 42 mGy / min), and all of it was returned to the femoral vein after irradiation. In the same way, 10% of the whole body circulating blood volume was drawn from the 100mGy×10% group, 150mGy×10% group, 200mGy×10% group and control group, and then irradiated at 100, 150, 200 and 0mGy (false irradiation) irradiation doses, and all of it was returned to the femoral vein after irradiation. Changes in the number of peripheral blood leukocytes were detected once every two days.

[0048] like Figure 2As shown in the figure, after the autologous peripheral blood was irradiated with 100mGy X-rays in vitro and then transfused, the WBC of the 100mGy×5% group and the 100mGy×10% group gradually increased, and the WBC of the 100mGy×10% group was significantly higher than that of the 100mGy×5% group, and reached the first peak on d6 after transfusion (Figure A); after the autologous peripheral blood was irradiated with 150mGy X-rays in vitro and then transfused, the WBC of the 150mGy×5% group and the 150mGy×10% group gradually increased, and the WBC of the 150mGy×5% group reached a peak on d8 after transfusion and then gradually decreased. The WBC of the 150mGy×10% group reached a peak on d6 after transfusion and then gradually decreased. Before d8, the WBC in the 150mGy×10% group was significantly higher than that in the 150mGy×5% group (P<0.05, Figure B); after the autologous peripheral blood was irradiated with 200mGy X-rays in vitro and then transfused, the WBC in the 200mGy×5% and 200mGy×10% groups showed a certain upward trend on d2, and the WBC in the 200mGy×5% group began to decrease on d4 after transfusion, reaching a peak on d8 and then decreasing. The WBC in the 200mGy×10% group reached a peak on d2 and then gradually decreased. Before d8, the WBC in the 200mGy×10% group was significantly higher than that in the 200mGy×5% group (P<0.05, Figure C);

[0049] Figure 2 AC results showed that before d8, under the same radiation dose, the WBC counts of the groups using 10% of the autologous circulating blood volume for in vitro irradiation and transfusion were generally higher than those of the groups using 5% of the autologous circulating blood volume. Therefore, this study selected 10% of the autologous circulating blood volume as the subsequent experimental condition.

[0050] Under the condition of 10% blood transfusion, the WBC count of the 100mGy×10% group was generally higher than that of the other groups; the 150mGy×10% group was second; and the WBC count of the 200mGy×10% group was generally lower than that of the control group except for d2 (Figure D). Therefore, in subsequent experiments, this study chose to transfuse 10% of the autologous circulating blood volume and set the autologous blood in vitro irradiation dose to 100mGy.

[0051] sum Figure 1 and Figure 2 As a result, the WBC of the 1Gy group reached the valley value on d5 ( Figure 1 ), 100mGy×10% group reached the first peak on d6 ( Figure 2 A), in subsequent experiments, low-dose irradiated autologous peripheral blood was reinfused (LDIAPBR) 1 day before modeling.

[0052] Example 4 Effects of 100 mGy irradiation and 10% blood transfusion on rats

[0053] SD rats were randomly divided into normal group, model group, positive drug group (rhG-CSF), and low-dose irradiated autologous peripheral blood transfusion group (LDIAPBR), with 9 rats in each group. After 3 days of normal feeding and adaptation to the environment, 10% of the circulating blood volume of rats in the LDIAPBR group was drawn from the femoral artery into a citrate anticoagulation tube, and the puncture site was pressed with a cotton ball, and the indwelling needle was withdrawn. The blood in the anticoagulation tube was irradiated at a dose of 100mGy, and after irradiation, all of it was transfused into the femoral vein. At the same time, the blood drawn from the normal group and model group was not subjected to low-dose irradiation, and the rest of the operations were the same as those of the LDIAPBR group. The time of autologous peripheral blood transfusion was set as d0. On d1, rats in all groups except the normal control group were irradiated with 1Gy X-rays for whole body modeling. Rats in the positive drug group were subcutaneously injected with rhG-CSF 5μg / kg on d2 for 2 consecutive days.

[0054] Observe the general changes of rats every day, such as mental state, fur, stool, etc., record the changes in rat weight, and draw a weight change curve. Blood was collected from the medial canthus vein of the rats on d5, and blood routine was tested using a hematology analyzer. Rats in each group were deeply anesthetized with sodium pentobarbital and humanely euthanized. The thymus and spleen were removed, placed in physiological saline to remove the surface tissue, and the surface liquid was blotted with filter paper and then weighed and recorded. The thymus index and spleen index were calculated according to the following formula.

[0055] Thymus index or spleen index = thymus or spleen weight (mg) / body weight (g).

[0056] The rats were anesthetized and killed by cervical dislocation, and soaked in 75% alcohol for 5 minutes. The right femur was removed under sterile conditions, and the muscles and connective tissue on the femur were removed. 1mL RPMI1640 culture medium was extracted with a syringe, and the bone marrow was flushed from the bone marrow cavity into a 1.5mL sterilized EP tube. Repeat 3-5 times to ensure that the bone marrow was completely flushed out, and repeatedly blown to form a single cell suspension. 10uL of cell liquid was drawn with a pipette, dropped on the abalone counting plate, and bone marrow nucleated cells (BMNC) were counted under a microscope. Then the cell suspensions of each group were combined into 15mL centrifuge tubes, mixed, and counted on the abalone counting plate. An appropriate amount of cell suspension was taken to adjust the cell density to 1×10 6 / mL, and spread on a 96-well plate, with 6 replicate wells in each group. Add 10 μL of CCK-8 solution to each well, mix thoroughly, incubate in a 37°C cell culture incubator for 4 hours, shake thoroughly, and measure the absorbance at 450 nm on an ELISA reader to determine the activity of bone marrow nucleated cells.

[0057] The left femur of the rat was removed and fixed in 4% paraformaldehyde for 24 hours, then decalcified, dehydrated, paraffin-embedded, sliced, and sealed after H&E staining. Finally, images were taken under an optical microscope.

[0058] like Figure 3 As shown in the figure, rats in the LDIAPBR group showed a significant improvement effect. Compared with the model group, the overall condition of the rats in the LDIAPBR group was better, similar to that of the positive drug group. In terms of weight changes, the LDIAPBR group showed a more obvious recovery trend during the recovery process after modeling: before irradiation, there was no significant difference in the weight of rats in each group. On d1 after modeling, except for the positive drug group, the weight of rats in the other groups began to decrease. The weight of the model group on d2 dropped to the lowest point (197.00±10.30) g, which was significantly lower than that of the normal group (211.33±6.08) g. Subsequently, the weight of each group began to recover, among which the recovery speed of the LDIAPBR group and the positive drug group was second only to the normal group and significantly faster than the model group. The weight recovery effect of the LDIAPBR group gradually emerged. The weight of the LDIAPBR group on d3 (213.56±6.33) g showed an upward trend compared with the model group (211.11±6.97) g, and the weight of the LDIAPBR group on d4 (237.78±12.22) g was significantly higher than that of the model group (221.67±10.20) g. The weight recovery trend of the LDIAPBR group was similar to that of the positive drug group, and the positive drug group showed significant weight gain on d3 and d4.

[0059] Compared with other groups, the model group rats performed poorly throughout the observation period, with reduced food intake, coarse hair, listlessness, significant weight loss, and dark brown and dry feces. The normal group rats, on the other hand, remained in good condition, with shiny hair, agile movements, and soft and shiny feces.

[0060] The spleen and thymus are key hematopoietic and immune organs, and their indexes reflect the functional status of these two organs. Figure 4 As shown in the figure, the spleen index of the model group was (2.14±0.31), which was significantly lower than that of the normal group (3.35±0.07); the spleen indexes of the LDIAPBR group and the positive drug group were (2.10±0.35) and (2.08±0.37), respectively, which were not significantly different from those of the model group (2.14±0.31). Figure 4 A). The thymus index of the model group (1.67±0.37) was significantly lower than that of the normal group (1.97±0.11); the thymus index of the LDIAPBR group and the positive drug group were (1.71±0.27) and (2.00±0.44), respectively, which were higher than that of the model group (1.67±0.37), but there was no significant difference ( Figure 4 B).

[0061] like Figure 5 As shown, the LDIAPBR group showed a significant effect in improving the peripheral blood cell count after modeling. Compared with the model group, the number of white blood cells and lymphocytes in the LDIAPBR group increased significantly, and the neutrophils also showed an upward trend. This improvement effect was similar to that of the positive drug group, which also showed a significant increase in the number of white blood cells and lymphocytes, as well as an upward trend in neutrophils. The number of white blood cells, lymphocytes, and neutrophils in the peripheral blood of the model group was significantly reduced compared with the normal group, and the intervention of LDIAPBR effectively alleviated this phenomenon (see Table 1, Figure 5 AC). However, prophylactic treatment with LDIAPBR did not significantly affect other peripheral blood parameters, such as red blood cell count, hemoglobin concentration, and platelet number, which was similar to the situation after modeling ( Figure 5 -DF).

[0062] Table 1 Results of peripheral blood leukocyte, lymphocyte and neutrophil counts in rats

[0063]

[0064] * indicates P<0.05 compared with the model group, *** indicates P<0.001 compared with the model group

[0065] like Figure 6 As shown in Figure 1, the number and status of bone marrow nucleated cells directly reflect the hematopoietic function of the bone marrow. The number of bone marrow nucleated cells in the LDIAPBR group was (5.967±2.326)×10 7 Compared with the model group (2.876±2.292)×10 7 The number of bone marrow nucleated cells in the model group was (2.876±2.292)×10 7 Compared with the normal group (5.975±1.829)×10 7 The results showed that the intervention of LDIAPBR effectively alleviated the decrease in the number of bone marrow nucleated cells, indicating that it has the effect of protecting the hematopoietic function of the bone marrow. Similarly, the bone marrow cell activity of the LDIAPBR group (97.325±4.177)% was significantly higher than that of the model group (85.063±1.709)%. The cell activity of the model group was significantly lower than that of the normal group, and LDIAPBR successfully reversed this trend, proving the positive role of LDIAPBR in maintaining the activity of bone marrow cells.

[0066] Compared with the model group (2.876±2.292)×10 7 In contrast, the number of bone marrow nucleated cells in the positive drug group was (4.389±1.683)×10 7Although there was an upward trend, the difference between the two did not reach a statistically significant level, but was significantly lower than that of the LDIAPBR group (5.967±2.326)×10 7 This indicates that the LDIAPBR group was even better than the positive drug group in improving the number of bone marrow nucleated cells.

[0067] Compared with 85.063±1.709)% in the model group, the cell viability in the positive drug group was (98.81±5.18)%, showing a significant effect, which was similar to that in the LDIAPBR group (97.325±4.177)%.

[0068] like Figure 7 As shown in the figure, the nucleated cells in the bone marrow tissue of the normal group rats were dense, sparsely distributed, and the overall structure was clear and complete. The number of nucleated cells in the model group was significantly reduced, the cavity area was larger, and the distribution was uneven, showing an obvious pathological state. The nucleated cells in the LDIAPBR group were evenly distributed, the density was significantly increased, the cavity area was reduced, the overall structure was close to the normal group, and the bone marrow tissue state was significantly better than the model group. The improvement effect of the LDIAPBR group on the bone marrow tissue damage in rats was comparable to that of the positive drug group, and both showed a protective effect on the bone marrow tissue.

[0069] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

Claims

1. Use of irradiated blood products in the preparation of products for preventing or treating leukopenia, wherein the irradiated blood products are obtained after irradiation with a dose of ≤300mGy.

2. The use according to claim 1, characterized in that: The leukopenia is leukopenia caused by radiation or drugs.

3. The use according to claim 1, characterized in that: The radiation dose of the rays is 100 to 300 mGy.

4. The use according to claim 1, characterized in that: The blood products include whole blood or blood components.

5. The use according to claim 1, characterized in that: The blood sample is autologous peripheral blood.

6. Use of a radiation source in the preparation of a device for preventing or treating leukopenia, wherein the device comprises the radiation source, and the radiation dose adjustment range of the radiation generated by the radiation source is ≤300mGy.

7. The use according to claim 6, characterized in that: The leukopenia is leukopenia caused by radiation or drugs.

8. The use according to claim 6, characterized in that: The radiation dose generated by the radiation source can be adjusted to 100-300 mGy.

9. A blood irradiation device for treating ex vivo blood, characterized in that: The blood irradiation device comprises an irradiation source, and the dose adjustment range of the irradiation rays generated by the irradiation source is ≤300mGy.

10. The blood irradiation device according to claim 9, characterized in that: The radiation dose generated by the radiation source can be adjusted to 100-300 mGy.

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