CN114129722B - Application of human immunoglobulin for injection in preparation of medicament for preventing or treating radiation injury - Google Patents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention discloses application of human immunoglobulin for injection in preparing a medicament for preventing or treating radiation injury, belonging to the field of biological products. The application of the invention is a brand new application of intravenous injection human immunoglobulin, and the intravenous injection human immunoglobulin can prevent or treat organism injury caused by rays before or after the human or animal body is irradiated, and has important application value in tumor radiotherapy and injury rescue caused by nuclear leakage.
Description
Technical Field
The invention belongs to the field of biological products.
Background
Cancer is the second leading cause of death in humans worldwide. Radiation therapy (abbreviated as "radiotherapy") is widely used as an effective therapeutic means for tumor therapy. Radiation therapy relies primarily on high energy radiation or particle beams for treatment of almost all types of tumors. Radiation therapy is the treatment of choice for some tumors, such as nasopharyngeal carcinoma. About 70% of tumor patients worldwide need radiation therapy as a primary or secondary treatment in the course of their treatment, and about 40% can be radically cured by radiation therapy. The contribution rate of radiation therapy to tumor treatment is as high as 18%, which is inferior to surgical treatment and significantly higher than chemotherapy and biological treatment, so that it can be seen that radiation therapy is important in the treatment process of tumor patients.
Inevitably, radiation therapy gives the body varying degrees of radiation damage, mainly manifested by acute injury represented by inflammation and chronic organ injury represented by fibrosis. In particular, radiation treatment of head and neck tumors often leads to oral mucositis; chest tumor radiation therapy often results in chronic pneumonia; radiation therapy of pelvic and abdominal tumors often causes diarrhea, chronic enteritis, intestinal obstruction, and the like. Hematopoietic injuries represented by leucopenia and marrow system shifts, and digestive tract injuries represented by enteritis and intestinal obstruction are common in radiation therapy at multiple sites. These side effects will lead to premature termination of radiation therapy, severely reducing the quality of life of the patient and even causing death of the patient. Acute and chronic injury show a progressive relationship in that organ and systemic chronic inflammation will lead to the onset of organ fibrosis. Increasing the dose of radiation therapy will also inevitably increase the risk of developing acute and chronic radiation damage to healthy organs. Therefore, the method reduces the acute and chronic irradiation damage accompanied by the radiotherapy, promotes the clinical application of the radiotherapy to a greater extent, and improves the life quality of prognosis of tumor patients.
The rapid development of nuclear technology and nuclear industry makes nuclear energy increasingly widely used in industrial and agricultural production, scientific and technical research and national defense and civil engineering. The peace use of "nuclear" has become an unavoidable development impetus for countries around the world. The occurrence of nuclear accidents (such as the carnubeli event and the fukushima event), which are the states of deviation from the operating conditions in nuclear facilities or nuclear activities, will cause unexpected and involuntary irradiation to radioactive staff and surrounding people, resulting in irradiation damage. The damage has long duration and wide scope, and can cause great mental panic and disorder of socioeconomic order of people. How to rapidly cure people suffering from radiation injury is not only related to personal health, but also related to social stability and national strategy.
The human immunoglobulin for injection is prepared from healthy human plasma by separating and purifying, removing anticomplement activity, inactivating virus, and freeze-drying to obtain immunoglobulin product, and the main active ingredient is polyclonal immunoglobulin combination aiming at various exogenous antigens and autoantigens. Human immunoglobulins for injection can be administered in the following manner: intravenous (intravenous immunoglobulin, IVIg), intramuscular (intramuscular immunoglobulin, IMIg) and subcutaneous (subcutaneous immunoglobulin, SCIg) injection of human immunoglobulin. The human immunoglobulin for injection is an effective medicament for treating primary immunodeficiency, secondary immunodeficiency and autoimmune diseases (Kawasaki disease and idiopathic thrombocytopenic purpura) and has wide clinical application.
At present, the report of the human immunoglobulin for injection for treating irradiation injury is not yet seen.
Disclosure of Invention
The invention aims to solve the problems that: provides the use of IVIg in preparing medicine for preventing or treating irradiation damage.
The technical scheme of the invention is as follows:
use of human immunoglobulin for injection in preparing medicament for preventing or treating radiation injury.
The use as described above, wherein the human immunoglobulin for injection is intravenous, intramuscular or subcutaneous.
The use as described above, wherein the human immunoglobulin for injection is intravenous human immunoglobulin.
The use as described above, wherein the IgG content of the intravenous human immunoglobulin is 95% or more of the protein content.
The use as described above, wherein the irradiation damage is irradiation resulting in thymus atrophy, spleen atrophy, infection, inflammation, tissue damage or reduced intestinal length. The use as described above, wherein the medicament is a female medicament or a female medicament.
A combination for the treatment of a tumor, said combination comprising a radiation therapy and human immunoglobulin for injection.
The combination according to the above, wherein the human immunoglobulin for injection is intravenous human immunoglobulin, intramuscular human immunoglobulin or subcutaneous human immunoglobulin.
The combination according to the preceding, wherein the human immunoglobulin for injection is intravenous human immunoglobulin; preferably, the IgG content of the intravenous human immunoglobulin is more than 95% of the protein content.
The combination according to the preceding claim, which is a female drug or a female drug.
The beneficial effects of the invention are as follows:
the human immunoglobulin for injection can relieve damage of irradiation to thymus and spleen, help to maintain hematopoietic function, maintain lymphocyte number, reduce in vivo infection, inflammation or tissue injury, relieve or reverse symptoms such as large intestine shortening (large intestine shortening is a manifestation of enteritis) caused by irradiation, further prevent or treat damage caused by irradiation, promote organism recovery, and remarkably improve survival rate of organism after lethal irradiation.
The human immunoglobulin for injection is used for preparing the medicine for preventing or treating radiation injury, and has important significance for tumor patients receiving radiotherapy and wounded suffering from radiation.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
Fig. 1: effect of IVIg intervention on survival of lethal dose irradiated mice for 30 days.
Fig. 2: effect of IVIg intervention on 30 day survival of lethal dose irradiated male and female mice; a, male; b, female.
Fig. 3: effect of IVIg on thymus after mouse irradiation; a, male; b, female.
Fig. 4: effect of IVIg on spleen after mouse irradiation; a, totality; b, female; c, male.
Fig. 5: effect of IVIg on lymphocytes after irradiation; a, pre group; and B, post group.
Fig. 6: effect of IVIg on neutrophils after irradiation; a, pre group; and B, post group.
Fig. 7: effect of IVIg treatment on the intestinal tract of radiation-injured mice; a, female; b, male.
Detailed Description
The IVIg used in the examples was given away by Shandong Thai biological products Co., ltd, and its IgG content was 98% or more of the total protein content.
Example 1IVIg intervention significantly improved 30 day survival of lethally irradiated mice (simulated accidental irradiation)
1. Method of
72 mice were divided into TBI, pre and Post groups of 24 mice each (of which female mice 12 and male mice 12). Three groups were subjected to a lethal dose of total body irradiation at 7.2Gy, except:
the TBI group was irradiated only and IVIg was not injected;
the Pre group (prophylaxis group) was given by IVIg 1 time within 30min before irradiation, followed by 2 weekly administrations;
post group (treatment group) was administered 1 time within 30min after irradiation, followed by 2 times per week.
The administration is as follows: the IVIg dose was 0.3g/Kg body weight.
2. Results
(1) IVIg intervention significantly improves 30-day survival of lethal dose irradiated mice
As shown in fig. 1, 24 mice in TBI group survived 2 days after the lethal dose of whole body irradiation, with a survival rate of 8.33%; 4 mice survived in the Pre group, with a survival rate of 16.67%; post group 24 mice survived 17 mice with a survival rate of 70.83%. Survival rates were significantly higher for 30 days than for the TBI group, either Pre (prophylaxis) or Post (treatment) groups.
(2) IVIg intervention was better in female than in male mice
After the male mice were irradiated with lethal dose (fig. 2A), 12 mice in TBI group and Pre group survived 0 after 30 days, with survival rate of 0; post group 12 mice survived 5 mice with a survival rate of 41.67%. IVIg prophylaxis (Pre) was not effective in male mice, but treatment (Post) significantly increased 30 day survival.
Female mice survived lethal dose irradiation (fig. 2B), with 2 mice survived 30 days in TBI group with a survival rate of 16.67%; 4 mice survived in Pre group 12, with a survival rate of 33.33%; 12 mice survived 12 in Post group with 100% survival rate. Both the IVIg prophylactic (pre-irradiation injection) and therapeutic (Post-irradiation injection) treatments improved 30-day survival of female mice, especially with the therapeutic (Post group) treatment being excellent in female mice.
The results of this example show that: the survival rate of the organism can be improved by injecting IVIg before and after the lethal dose of irradiation, which indicates that the IVIg can effectively prevent or treat irradiation damage and is sufficient for first aid after the lethal dose of irradiation. In addition, the effect of IVIg on female mice was more pronounced than on male mice, and it was concluded that the effect on females was better than on males when humans were used.
EXAMPLE 2 treatment of IVIg on radiation-damaged mice (simulated accidental radiation)
1. Method of
52 mice were divided into Con (control, no irradiation, no dosing), TBI, pre and Post groups, 13 each (7 female mice, 6 male mice). Three groups were subjected to total body irradiation at a dose of 4Gy, blood images were analyzed after 15 days, thymus and spleen were analyzed after sacrifice and dissection. The differences are:
the Con group was not irradiated and IVIg was not injected;
the TBI group was irradiated only and IVIg was not injected;
the Pre group (prophylaxis group) was given by IVIg 1 time within 30min before irradiation, followed by 2 weekly administrations;
post group (treatment group) was administered 1 time within 30min after irradiation, followed by 2 times per week.
The administration is as follows: the IVIg dose was 0.3g/Kg body weight.
2. Results
(1) Thymus observation
Compared to the Con group, after 15 days of systemic irradiation at a dose of 4Gy, the thymus in the TBI group was significantly atrophic, and the thymus sizes in the Pre and Post groups were restored (fig. 3B), both in the male mice (fig. 3A) and in the female mice.
(2) Spleen observations
Compared to the Con group, the TBI group showed a significant decrease in spleen weight after 15 days of whole body irradiation at a dose of 4Gy (fig. 4A). Spleen weights were increased in both Pre and Post groups compared to TBI.
In female mice (fig. 4B), spleen weights were significantly elevated in both Pre and Post groups compared to TBI group. In male mice (fig. 4C), spleen weights in Pre and Post groups both tended to increase compared to TBI group, but there was no statistical difference.
(3) Lymphocyte observation
Compared to the Con group, the TBI group lymphocyte numbers were significantly reduced after 15 days of whole body irradiation at a dose of 4Gy (fig. 5). The lymphocyte numbers were significantly increased in both the Pre (FIG. 5A) and Post (FIG. 5B) groups compared to the TBI group.
Thymus and spleen are important immune organs and hematopoietic organs of human body, and the original sources of lymphocytes are hematopoietic organs, so that the higher the number of lymphocytes, the stronger the hematopoietic function.
The results of the above parts (1) to (3) show that:
IVIg can prevent and treat thymus and spleen injury (atrophy of appearance, and impaired hematopoiesis) caused by irradiation.
(4) Neutrophil observation
Compared to the Con group, the number of neutrophils in the TBI group was significantly increased after 15 days of whole body irradiation at a dose of 4Gy (fig. 6). Compared to the TBI group, the neutrophil count was significantly reduced in both the Pre group (fig. 6A) and Post group (fig. 6B), especially Post group, to almost normal levels.
Neutrophils have chemotactic, phagocytic and bactericidal effects, and an increased number often indicates symptoms such as infection, inflammation or tissue damage in the body.
The results of the above (4) indicate that: administration of IVIg prophylaxis or treatment may significantly ameliorate symptoms of infection, inflammation or tissue damage caused by irradiation to mice, particularly female mice.
The results of this example show that: after irradiation injury, IVIg is administered for preventing or treating, so that immune and hematopoietic organs such as thymus, spleen and the like of mice (especially female mice) can be obviously improved, hematopoietic functions can be protected, and irradiation-related infection, inflammation and tissue injury can be reduced.
EXAMPLE 3 treatment of IVIg on Abdominal radiation injured mice (mock radiation treatment)
1. Method of
30 mice were divided into Con (control, no irradiation, no dosing), TBI, IVIg (treatment) groups of 10 mice each (5 female mice, 5 male mice). The three groups were subjected to local abdominal irradiation at a total dose of 12Gy, and after 21 days, the intestinal tract length changes were sacrificed and anatomically analyzed. The differences are:
the Con group was not irradiated and IVIg was not injected;
the TBI group was irradiated only and IVIg was not injected;
the IVIg group (treatment group) was administered 1 time within 30min after irradiation, followed by 2 times per week.
The administration is as follows: the IVIg dose was 0.3g/Kg body weight.
2. Results
Whether in female or male mice, the length of the large intestine was significantly shortened after the total 12Gy abdominal local irradiation, and this condition was significantly improved after IVIg treatment (fig. 6).
The results of this example demonstrate that IVIg can alleviate symptoms of reduced large intestine length caused by irradiation.
In conclusion, IVIg can reduce injury of irradiation to spleen and thymus, ensure hematopoietic function, maintain lymphocyte number, reduce infection, inflammation and tissue injury caused by irradiation, relieve symptoms of reduced length of large intestine caused by irradiation, and can be used for preventing or treating irradiation injury and improving survival rate under lethal irradiation. Other human immunoglobulins for injection, such as intramuscular injection human immunoglobulin and subcutaneous injection human immunoglobulin, have the same basic components as IVIg, and thus have similar functions to IVIg in preventing and treating irradiation damage.
Claims (4)
1. Use of human immunoglobulin for injection in preparing a medicament for preventing or treating radiation injury; the irradiation damage is the reduction of the length of the intestinal tract caused by irradiation.
2. The use according to claim 1, characterized in that: the human immunoglobulin for injection is intravenous injection human immunoglobulin, intramuscular injection human immunoglobulin or subcutaneous injection human immunoglobulin.
3. The use according to claim 1, characterized in that: the human immunoglobulin for injection is intravenous human immunoglobulin.
4. A use according to claim 3, wherein: the IgG content of the intravenous injection human immunoglobulin accounts for more than 95% of the protein content.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5562902A (en) * | 1994-03-14 | 1996-10-08 | Arp Biomed, Inc. | Immunotherapeutic method of treating cancerous diseases by administration of intravenous immunoglobulin |
| RU2011150766A (en) * | 2011-12-13 | 2013-06-20 | Федеральное государственное бюджетное учреждение "Федеральный Центр токсикологической, радиационной и биологической безопасности" (ФГБУ "ФЦТРБ-ВНИВИ") | METHOD FOR TREATING RADIATION-CHEMICAL-BIOLOGICAL DAMAGE OF THE ORGANISM AND METHOD FOR PRODUCING GLOBULINS FOR TREATMENT OF RADIATION-CHEMICAL-BIOLOGICAL DAMAGE OF THE ORGANISM |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5562902A (en) * | 1994-03-14 | 1996-10-08 | Arp Biomed, Inc. | Immunotherapeutic method of treating cancerous diseases by administration of intravenous immunoglobulin |
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