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Application of VEGF acceptor fusion proteins in preparation of drugs for inhibiting growth of ocular surface neovascularization

A fusion protein and drug technology, applied in drug combinations, peptide/protein components, antibodies, etc., can solve the problems of no better treatment for diseases, patient impact, and no prevention and treatment of corneal neovascularization

Active Publication Date: 2013-10-23
CHENGDU KANGHONG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Chinese patent ZL200510073595.4 discloses the structure and preparation method of fusion protein FP1-FP6 and its anti-tumor application, as well as its use in retinopathy, but does not involve the prevention and treatment of corneal neovascularization
Chinese patent ZL200610066257.2 discloses the structure of the fusion protein FP1-FP8 and its preparation method, as well as its application in the preparation of drugs for the treatment of ophthalmic diseases caused by the growth of new blood vessels. It also does not involve VEGFR fusion proteins FP1, FP3, Application of FP7 and FP8 in the preparation of drugs for treating corneal neovascularization
At present, there is no good treatment for this type of disease. Although it can be treated surgically, it has a great impact on patients, and there is an urgent need for safe and effective prevention and treatment drugs.

Method used

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  • Application of VEGF acceptor fusion proteins in preparation of drugs for inhibiting growth of ocular surface neovascularization
  • Application of VEGF acceptor fusion proteins in preparation of drugs for inhibiting growth of ocular surface neovascularization
  • Application of VEGF acceptor fusion proteins in preparation of drugs for inhibiting growth of ocular surface neovascularization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Therapeutic effect and safety test of fusion protein on corneal angiogenesis induced by alkali burn

[0032] Establish an animal model of corneal angiogenesis in rats (SD rats, female, body weight 250g±20g) by alkali burn method, and study the inhibitory effect of fusion proteins FP1, FP3, FP7 and FP8 on corneal angiogenesis induced by alkali burn .

[0033] Take a rat, take the right eye as the experimental eye under anesthesia, stick a filter paper piece with a diameter of 3 mm soaked in 1mol / L NaOH solution to the center of the cornea of ​​the rat, remove the filter paper piece after acting for 1 minute, and use a large amount of The conjunctival sac was washed with normal saline to remove residual NaOH, and 20ul of chloramphenicol eye drops (manufacturer: Changzhou Siyao Pharmaceutical Co., Ltd., specification 8ml: 20mg) and 1% atropine eye ointment were added dropwise.

[0034] The next day, the rats were equally divided into 7 groups (6 rats in each gro...

Embodiment 2

[0043] Example 2 Therapeutic effect and safety of fusion protein on herpes simplex virus keratitis

[0044] A corneal scratching method was used to prepare an animal model in which the cornea of ​​a mouse (BalB / C mouse, female, 6-8 weeks old, weighing 20-25 g) was infected with herpes simplex virus.

[0045] HSV was subcultured on Vero cells and quantified by conventional methods. The right eye of the mouse was used as the experimental eye. Under anesthesia, the mouse was dipped in 2 μl of HSV-1 virus liquid (containing about 5×10 5 PFU (herpes simplex virus type 1) micropipette needle, gently scratch the animal's cornea and massage the conjunctiva.

[0046] The experimental animals were divided into 7 groups (8 animals in each group), namely FP1 group, FP3 group, FP7 group, FP8 group, drug carrier group, dexamethasone group and normal saline group (NS). Among them, the administration concentration of the fusion protein in the FP1, FP3, FP7 and FP8 groups was 10 mg / ml, which...

Embodiment 3

[0054] Example 3 Inhibitory effect of fusion protein on mouse corneal angiogenesis induced by surgical sutures

[0055] The animal model of corneal angiogenesis was established by implanting surgical sutures in the corneal stroma of mice.

[0056] Take 6-week-old male BalB / c mice, weighing 18-25 g, under anesthesia, take the right eye as the experimental eye, and plant 3 surgical sutures (11-0 nylon thread) in the corneal stroma (each The line starts near the limbus and ends in the central area of ​​the cornea, and the angle between two adjacent lines is 120°).

[0057] Three days after suture implantation, the animals were divided into the following 7 groups (6 animals each), namely, FP1 group, FP3 group, FP7 group, FP8 group, drug vehicle group, dexamethasone group, and normal saline group (NS). Among them, the administration concentration of the fusion protein in the FP1, FP3, FP7 and FP8 groups was 10 mg / ml, which was diluted with PBS solution before use; the drug carrier...

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Abstract

The invention relates to the application of VEGFR fusion proteins FP1, FP3, FP7 and FP8 in the preparation of drugs for treating ocular surface neovascularization and relevant diseases and a combined preparation of fusion proteins FP1, FP3, FP7, FP8 and an immunosuppressant, wherein the immunosuppressant is one or a combination selected from the group consisting of corticosteroid, rapamycin, dexamethasone and cyclosporine A; and amino acid sequences of FP1, FP3, FP7 and FP8 are respectively as shown in SEQ ID NO:1, 2, 3, 4.

Description

technical field [0001] The present invention relates to the medical application of vascular endothelial cell receptor (Vascular Endothelial Growth Factor receptor, VEGFR) fusion protein, in particular to the application of VEGFR fusion protein in the preparation of medicines for treating diseases caused by the growth of new blood vessels on the ocular surface. Background technique [0002] The cornea and conjunctiva on the ocular surface are susceptible to various stimuli, including microbial infection, physical impact, chemical composition damage, corneal friction damage caused by contact lenses, corneal hypoxia, etc., which will lead to corneal or conjunctival lesions. Table new blood vessels. Diseases associated with neovascularization of the ocular surface include corneal neovascularization, neovascular glaucoma, pterygium, conjunctivitis, bacterial keratitis, fungal keratitis, viral keratitis, bullous keratoconjunctivitis, corneal ulcer, scleritis , Corneal contact len...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/395A61K45/00A61P27/02A61P27/06A61P31/04A61P31/12A61P31/22A61K38/18A61K31/573
Inventor 俞德超
Owner CHENGDU KANGHONG BIOTECH
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