Combination Drugs of Lachnospiraceae Bacteria and Human Immunoglobulin

Abstract

A combined drug contains Lachnospiraceae bacteria and human immunoglobulin (HIg). HIg has a therapeutic effect on radiation injuries, and the combination of Lachnospiraceae bacteria and HIg can further improve this therapeutic effect. The combination drug can be administered to patients who were undergoing radiotherapy and to people who accidentally receive excessive irradiation.

Claims

1. A combined drug for the treatment of radiation injuries, characterized in that the combined drug contains Lachnospiraceae bacteria and human immunoglobulin (HIg) with the same or different specifications, that are administered simultaneously or separately; said HIg includes intravenous immunoglobulin (IVIg), intramuscular immunoglobulin (IMIg) and/or subcutaneous immunoglobulin (SCIg).

2. The combined drug according to claim 1, characterized in that said Lachnospiraceae bacteria are those with ATCC number BAA-2278.

3. The combined drug according to claim 1, characterized in that said combined drug is the one that restores the hematopoietic function of the body after radiation injuries.

4. The combined drug according to claim 1, characterized in that said combined drug is the one that retards thymic atrophy, spleen atrophy, leukocytopenia and/or inflammation caused by radiation injuries.

5. The combined drug according to claim 1, characterized in that said combined drug is for male (including human and animals).

6. Use of a combined drug according to claim 1 in the preparation of a medicament for reducing radiation injuries.

7. A combined drug for treating tumors, characterized in that the combined drug contains anti-tumor radiotherapy drugs, Lachnospiraceae bacteria and HIg with the same or different specifications, that are administered simultaneously or separately; said HIg includes intravenous immunoglobulin (IVIg), intramuscular immunoglobulin (IMIg) and/or subcutaneous immunoglobulin (SCIg).

8. The combined drug according to claim 7, characterized in that said Lachnospiraceae bacteria are those with ATCC number BAA-2278.

9. The combined drug according to claim 7, characterized in that said combined drug is the one that restores the hematopoietic function of the body after radiotherapy.

10. The combined drug according to claim 7, characterized in that said combined drug is the one that retards thymic atrophy, spleen atrophy, leukocytopenia and/or inflammation caused by radiotherapy; preferably, said combined drug is for male (including human and animals).

Description

DESCRIPTION OF FIGURES

[0031] FIG. 1: The appearance of the thymus.

[0032] FIG. 2: The appearance of the spleen.

[0033] FIG. 3: Leukocyte count in peripheral blood.

[0034] FIG. 4: The appearance of the large intestine in TAI group and Lachnospiraceae group.

[0035] FIG. 5: Levels of TNF-α and IL-6 in the small intestine of TAI group and Lachnospiraceae group. The ordinate mL represents the volume of PBS used to extract TNF-α and IL-6 from the small intestine, and the volume of PBS used for each unit weight of the small intestine is consistent.

[0036] FIG. 6: The appearance of the large intestine in IVIg group and IVIg+Lachnospiraceae group.

[0037] FIG. 7: Levels of TNF-α and IL-6 in the small intestine of IVIg group and IVIg+Lachnospiraceae group. The ordinate mL represents the volume of PBS used to extract TNF-α and IL-6 from the small intestine, and the volume of PBS used for each unit weight of the small intestine is consistent.

EXAMPLES

Example 1. Use of the Combination of IVIg+Lachnospiraceae for the Treatment of Radiation Injuries

[0038] Lachnospiraceae used in this example are Lachnospiraceae bacteria with the number ATCC BAA-2278.

1. Method

1.1. Analysis of Hematopoietic System Injury by Total Body Irradiation at 5 Gy

[0039] 24 male mice were divided into two groups: [0040] 1) IVIg group, 12 mice; [0041] 2) IVIg+Lachnospiraceae group, 12 mice;

[0042] IVIg was administrated to IVIg group within 5 min after total body irradiation, followed by injecting IVIg twice a week for two weeks at a dose of 0.3 g/kg body weight. [0043] For IVIg+Lachnospiraceae group, Lachnospiraceae was orally given to mice within 30 min before total body irradiation, and then IVIg was administrated within 5 min after irradiation, followed by administrating IVIg twice a week for two weeks as well as orally giving Lachnospiraceae every two days. The dose of Lachnospiraceae was 1×10.sup.7; while the dose of IVIg was 0.3 g/kg body weight.
1.2. Analysis of Intestinal Injury by 12 Gy of Local Abdominal Irradiation 44 male mice were divided into 4 groups: [0044] 1) TAI group, 10 mice; [0045] 2) Lachnospiraceae group, 10 mice; [0046] 3) IVIg group, 12 mice; [0047] 4) IVIg+Lachnospiraceae group, 12 mice; [0048] TAI group received only local abdominal irradiation, and then PBS was injected to the mice in equal volume with other groups.

[0049] Lachnospiraceae was orally given to the mice in Lachnospiraceae group 30 min before local abdominal irradiation, followed by orally administration once every two days. The dose of Lachnospiraceae was 1×10.sup.7.

[0050] IVIg was intravenously injected into the mice in IVIg group within 5 min after local abdominal irradiation, followed by injection twice a week for two weeks at a dose of 0.3 g/kg body weight. Lachnospiraceae was orally administrated to the mice in IVIg+Lachnospiraceae group 30 min before local abdominal irradiation, and then IVIg was intravenously injected within 5 min after irradiation, followed by injecting IVIg twice a week for two weeks as well as orally giving Lachnospiraceae every two days. The dose of Lachnospiraceae was 1×10.sup.7; while the dose of IVIg was 0.3 g/kg body weight.

[0051] Then, peripheral blood was collected from mice to detect the number of white blood cells. Spleen, thymus and small intestine were taken for observation, and the levels of IL-6 and TNF-α in small intestine were further detected.

2. Results

[0052] Total body irradiation could lead to the atrophy of thymus and spleen, decrease in hematopoietic function, and subsequent reduction of white blood cells. As shown in FIGS. 1-3, the volumes of thymus and spleen as well as leukocyte numbers were significantly increased in IVIg+Lachnospiraceae group compared with IVIg group. The results indicated that the combination of IVIg and Lachnospiraceae could more obviously restore the size of thymus and spleen in mice compared with IVIg alone, and further lead to the recovery of hematopoietic function in irradiated mice.

[0053] Local abdominal irradiation could result in the shortening of the large intestine and the elevation of inflammatory factors TNFα and IL-6 in the small intestine in mice, leading to the occurrence of enteritis (Li et al., Gut commensal derived-valeric acid protects against radiation injuries. Gut Microbes, 2020, 11: 789-806). The length of the large intestine and the levels of inflammatory factors TNFα and IL-6 in the small intestine did not differ from that of TAI group (FIGS. 4 and 5), indicating that oral administration of Lachnospiraceae alone could not inhibit the radiation-induced inflammation. As shown in FIG. 6, the length of the large intestine in IVIg+Lachnospiraceae group was longer than that in IVIg group, and the levels of inflammatory cytokines TNFα and IL-6 in the small intestine were also lower than that in IVIg group (FIG. 7). This suggested that compared with the single use of IVIg, the combination of IVIg and Lachnospiraceae could further inhibit the radiation-induced inflammation.

[0054] The results of this example showed that Lachnospiraceae alone could not inhibit the radiation-induced inflammation, and compared with the administration of IVIg alone, the combination of IVIg and Lachnospiraceae could further inhibit the radiation-induced inflammation. In summary, the combination drug of the present invention can be used to restore the hematopoietic function of the body after irradiation, and can alleviate the atrophy of thymus and spleen, leukocytopenia and/or inflammation caused by irradiation; and the combination drug has overcome the disadvantage that IVIg alone cannot effectively treat male animals.