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Applications of platelet-related inhibitors in preparation of drugs for treating thrombocytopenia

A technology for thrombocytopenia, treatment medicine, applied in the field of medicine

Active Publication Date: 2018-12-18
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, about 15-25% of patients are not effective for IVIG or even splenectomy, and about 61% of patients still cannot maintain the platelet count at 30×10 after splenectomy. 9 / L or more, eventually progressing to refractory ITP

Method used

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  • Applications of platelet-related inhibitors in preparation of drugs for treating thrombocytopenia
  • Applications of platelet-related inhibitors in preparation of drugs for treating thrombocytopenia
  • Applications of platelet-related inhibitors in preparation of drugs for treating thrombocytopenia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The plasma of ITP patients is classified according to the different antibodies contained and then incubated with normal human platelets for detection. figure 1 for the result. The results showed that, compared with the control, anti-GPIbα antibody-positive ITP patient plasma can lead to a decrease in the mitochondrial membrane potential of normal human platelets ( figure 1 A), increased expression of P-selectin on platelet membrane surface ( figure 1 E) Simultaneously increased platelet membrane phosphatidylserine eversion ( figure 1B), and in the corresponding indicators of activation and apoptosis, ITP patient plasma containing anti-GPIIbIIIa antibody did not lead to a decrease in platelet mitochondrial membrane potential ( figure 1 A), P-selectin expression increased ( figure 1 E), PS eversion ( figure 1 B); figure 1 C. figure 1 D can also see the difference.

[0028] Human washed platelets were incubated with 10ug / ml antibody IgG, anti-GPIbα antibody AN51, an...

Embodiment 2

[0031] Human washed platelets were incubated in advance with GPIbα cluster inhibitors GlcNAc (100mM) and GM3 (100uM) at room temperature for 15 minutes, activation inhibitor BAPTA (10uM) at 37°C for 15 minutes, apoptosis inhibitor Q-VD-Oph (100uM)37 After 30 minutes at ℃, all groups were added with AN51 10ug / ml, and incubated at 37℃ for 8 hours to detect PS eversion. The same mouse PRP was incubated in advance with GPIbα cluster inhibitors GlcNAc (100mM) and GM3 (100uM) at room temperature After 15 minutes, activation inhibitor BAPTA (20uM) at 37°C for 15 minutes, apoptosis inhibitor Q-VD-Oph (100uM) at 37°C for 30 minutes, add R300 5ug / ml, and incubate at 37°C for 6 hours, then detect PS Eversion, mitochondrial membrane potential, P-selectin expression, see Figure 4 , the results showed that GlcNAc, GM3, BAPTA, and Q-VD-Oph could all inhibit the common pathway of platelet activation and apoptosis induced by AN51, PS eversion ( Figure 4 A) The mouse results are the same as ...

Embodiment 3

[0033] Separately mix the fluorescent secondary antibody with the control antibody, R300, R300F(ab) 2 After mixing, it was injected intraperitoneally into mice, and 4 hours later, the tissues and organs were taken out for observation with small animal live imaging; control antibodies, R300, and F(ab) were injected intraperitoneally, respectively. 2 After 4 hours, the liver was taken to make frozen sections, and macrophages were labeled with F4 / 80 (green), platelets were labeled with GPIbα (red), and nuclei were stained with DAPI (blue). The results are as follows Figure 5 shown.

[0034] Figure 5 A can see R300 and R300 F(ab) 2 Bound platelets are mainly accumulated in the liver; Figure 5 B results show that platelets mainly co-localize with macrophages; Figure 5 C shows that macrophages can be cleared with clodronate disodium liposomes, which can rescue the thrombocytopenia caused by intraperitoneal injection of R300; Figure 5 D shows that after clearing macrophage...

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Abstract

The invention discloses applications of platelet-related inhibitors in preparation of drugs for treating thrombocytopenia, wherein the platelet-related inhibitors comprise platelet activation inhibitors, platelet apoptosis inhibitors and platelet phagocytosis inhibitors, and the platelet-related inhibitors comprise anti-GPIb-IX and GPIIb / IIIa antibody binding inhibitors, GPIb[alpha] cluster inhibitors, intracellular calcium ion chelators, Caspase inhibitors, and phosphatidylserine receptor-ligand binding inhibitors. According to the present invention, the problem that the existing treatment scheme cannot provide treatment effect on patients with thrombocytopenia can be solved, and the platelet-related inhibitors can provide the new treatment targets for clinical refractory thrombocytopenia, and provides molecular theoretical basis and clinical treatment guidance.

Description

technical field [0001] The invention belongs to the technical field of medicines, and specifically relates to the application of a platelet activation inhibitor, a platelet apoptosis inhibitor or a platelet phagocytosis inhibitor in the preparation of a medicine for treating thrombocytopenia. The disclosed medicine for treating thrombocytopenia can effectively inhibit the decrease in the number of platelets. Background technique [0002] Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a decrease in the number of platelets, manifested by bleeding symptoms ranging from mild to severe. When the platelet count is below 10 x 10 9 / L, the risk of intracranial hemorrhage will be greatly increased, which is life-threatening. The first-line treatment of ITP includes glucocorticoids, intravenous immunoglobulin (intravenous immunoglobulin G, IVIG) and other immunosuppressive treatments. [0003] The pathogenesis of ITP is diverse and has not been fully elucida...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K39/395A61K38/07A61K38/06A61P7/04A61P37/02
CPCA61K38/06A61K38/07A61K39/395A61K45/00
Inventor 戴克胜
Owner SUZHOU UNIV
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