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Application of ABT-263 in preparation of medicine for inhibiting corneal transplantation immunological rejection

A technology of ABT-263, 1.ABT-263, applied in the field of chemical medicine

Pending Publication Date: 2021-11-12
山东第一医科大学附属青岛眼科医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are no reports on drugs that can effectively inhibit the aging and functional decline of corneal parenchymal cells and prevent decompensation of corneal endothelial cells in a timely and effective manner.

Method used

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  • Application of ABT-263 in preparation of medicine for inhibiting corneal transplantation immunological rejection
  • Application of ABT-263 in preparation of medicine for inhibiting corneal transplantation immunological rejection
  • Application of ABT-263 in preparation of medicine for inhibiting corneal transplantation immunological rejection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Immune rejection experiment after allogeneic corneal transplantation

[0031] 1. Randomly divide 18 BALB / c mice (6-8 weeks old) into the following 3 groups:

[0032] A. Normal group (Nor);

[0033] B. Syngeneic corneal transplantation group (Syn-transplantation, Syn);

[0034] C. Allo-transplantation (Allo-transplantation, Allo).

[0035] The penetrating keratoplasty model was constructed as follows: the right eye of all animals was selected as the operated eye. Before the operation, a slit lamp examination was performed to understand the condition of the operated eye, and levofloxacin eye drops were given to the operated eye to prevent infection. After the donor mouse was anesthetized by intraperitoneal injection of pentobarbital sodium, the 2.25mm corneal central full-thickness graft was taken under the operating microscope, and the 2.25mm central corneal penetrating implant bed of the recipient mouse was immediately implanted. 8 stitches were sutured intermittentl...

Embodiment 2

[0045] Deletion of aging gene p16 in corneal donors significantly prolongs the survival time of corneal grafts.

[0046] Cell senescence is mainly realized through two signaling pathways, p16INK4a / Rb and p19ARF / p53 / p21Cipl. In order to clarify the key role of aging in corneal transplant immune rejection, the present invention uses p16-deleted C57BL / 6 (Frederick National Laboratory for Cancer Research (FNL) / SAIC-Frederick, Inc) mice as corneal donors, Balb / C small Rats were used to construct penetrating keratoplasty models for corneal recipients to evaluate the effect of aging on immune rejection of corneal transplantation.

[0047] 1. Randomly divide 12 BALB / c mice (6-8 weeks old) into the following 2 groups:

[0048] A. Take wild-type C57B / L6 WT Allogeneic keratoplasty group (WT) as the donor;

[0049] B. Knockout mouse C57B / L6 with p16 p16KO Allograft keratoplasty group (p16KO) as graft donor.

[0050] A penetrating keratoplasty model was established, and the operation ...

Embodiment 3

[0056] Intervention of anti-aging drug ABT-263 significantly inhibits immune rejection of corneal transplantation

[0057] 1. Randomly divide 12 BALB / c mice (6-8 weeks old) into the following 2 groups:

[0058] A. Allogeneic corneal transplantation group (Allo);

[0059] B. Allogeneic corneal transplantation and ABT-263 injection group (Allo+ABT-263).

[0060] The penetrating keratoplasty model was established according to the method described in Example 1.

[0061] 3 days after operation, different drugs were injected according to different groups: group A PBS solution, group B ABT-263 (50mg / kg, 1 time / 2d), intraperitoneal injections were performed on the 2nd, 4th, 6th, 8th, and 10th days after operation, respectively. Injection, a total of 5 injections. On this basis, slit lamp observation was performed every day after operation, and the time of rejection in each group was recorded, and the survival curve of corneal grafts was drawn.

[0062] It was found through statist...

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Abstract

The invention provides application of ABT-263 in preparation of a medicine for inhibiting corneal transplantation immunological rejection, and belongs to the technical field of chemical medicines. The invention provides an application of a micromolecular Bcl-2 inhibitor Navitclax(ABT-263) capable of inducing apoptosis in preparation of a product for inhibiting immunological rejection after corneal transplantation. Researches show that the Bcl-2 inhibitor ABT-263 can prolong the survival time of a corneal graft after corneal transplantation, reduce immune inflammatory response in the corneal graft, maintain transparency of the corneal graft and reduce immunological rejection, and can be used for preventing and treating diseases such as immunological rejection after corneal transplantation, corneal endothelial cell decompensation and the like.

Description

technical field [0001] The invention belongs to the technical field of chemical drugs, and in particular relates to the application of ABT-263 in the preparation of drugs for inhibiting immune rejection of corneal transplantation. Background technique [0002] Corneal disease is one of the eye diseases with a high rate of blindness. Penetrating Keratoplasty (PK) is an important means of restoring vision for patients with corneal blindness, and it is also the last choice for preserving vision. Although the success rate of keratoplasty has been greatly improved with the improvement of microsurgical techniques, immune rejection after PK (especially high-risk keratoplasty) is still the main reason for corneal transplantation failure. Therefore, it has important clinical significance and value to prevent and treat immune rejection after PK surgery and maintain the transparency of corneal grafts. Due to the lack of blood vessels and lymphatic vessels, normal corneal tissue is in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5377A61K9/00A61P37/06
CPCA61K31/5377A61K9/0019A61P37/06
Inventor 史伟云韦超迟昊尹文慧白晓飞
Owner 山东第一医科大学附属青岛眼科医院
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