Unlock instant, AI-driven research and patent intelligence for your innovation.

Intravitreal injected microspheres with double protection against antibody drugs and preparation method thereof

A double-protection, anti-antibody technology, applied in the field of medicine, can solve problems such as the reduction of drug loading and encapsulation efficiency, antibody denaturation and aggregation, and large molecular weight of drugs, so as to improve denaturation and aggregation, reduce irritation, and improve patient compliance Effect

Active Publication Date: 2021-10-08
南京锐利施生物技术有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the large molecular weight and fragile structure of the drug, the organic phase / water phase interface generated during the preparation process is likely to cause denaturation and aggregation of antibodies, resulting in a decrease in drug activity.
Moreover, the drug in the inner water phase is easy to diffuse into the outer water phase due to hydrophilicity, resulting in lower drug loading and encapsulation efficiency.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Intravitreal injected microspheres with double protection against antibody drugs and preparation method thereof
  • Intravitreal injected microspheres with double protection against antibody drugs and preparation method thereof
  • Intravitreal injected microspheres with double protection against antibody drugs and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Note: Bev-PPsm in the experimental group is PLGA / PCADK microspheres loaded with bevacizumab prepared by S / O / W method; Bev-PPwm in the control group is loaded with bevacizumab prepared by W / O / W PLGA / PCADK microspheres of vacizumab; the control group Bev-Pwm is PLGA microspheres loaded with bevacizumab prepared by W / O / W method;

[0030] Bev-PPsm Prescription

[0031] Phase S: ​​bevacizumab-dextran microparticles (1:3), 50mg;

[0032] Phase O: PLGA 7525 4A, 80 mg; PCADK, 20 mg; Dichloromethane, 2 mL;

[0033] Phase W: 1.0% PVA aqueous solution, 10 mL;

[0034] Preparation process of Bev-PPsm

[0035] 1) Dissolve bevacizumab, dextran and PEG (1: 3: 40) in deionized water, vortex and then freeze-dry; the powder obtained after freeze-drying is washed by centrifugation with dichloromethane to remove the PEG dispersed phase, Vacuum drying to obtain bevacizumab-dextran microparticles;

[0036] 2) Dissolve PLGA and PCADK in dichloromethane, add the prepared particles, and ul...

Embodiment 2

[0050] Note: Afl-PPsm in the experimental group is the PLGA / PCADK microspheres loaded with aflibercept prepared by the S / O / W method; Afl-PPwm in the control group is prepared by the W / O / W method PLGA / PCADK microspheres of Aflibercept; the control group Afl-Pwm is PLGA microspheres loaded with Aflibercept prepared by W / O / W method;

[0051] Afl-PPsm prescription

[0052] Phase S: ​​Aflibercept-dextran microparticles (1:4), 40mg;

[0053] Phase O: PLGA 7525 4A, 70mg; PCADK, 30mg; Dichloromethane, 2 mL;

[0054] Phase W: 2.0% PVA aqueous solution, 15 mL;

[0055] Preparation process of Afl-PPsm

[0056] 1) Dissolve aflibercept, dextran and PEG (1:4:40) in deionized water, vortex and then freeze-dry; the powder obtained after freeze-drying is washed by centrifugation with dichloromethane to remove the PEG dispersed phase, Vacuum drying to obtain aflibercept-dextran microparticles;

[0057] 2) Dissolve PLGA and PCADK in dichloromethane, add the prepared particles, and ultrasonica...

Embodiment 3

[0071] Note: The experimental group Luc-PPsm is the PLGA / PCADK microspheres loaded with ranibizumab prepared by the S / O / W method; the control group Luc-PPwm is the ranibizumab-loaded microspheres prepared by the W / O / W method PLGA / PCADK microspheres of zizumab; the control group Luc-Pwm is PLGA microspheres loaded with ranibizumab prepared by W / O / W method;

[0072] Luc-PPsm Prescription

[0073] Phase S: ​​ranibizumab-dextran microparticles (1:5), 48mg;

[0074] Phase O: PLGA 7525 5A, 80mg; PCADK, 20mg; Dichloromethane, 2 mL;

[0075] Phase W: 1.0% PVA aqueous solution, 20 mL;

[0076] Preparation process of Luc-PPsm

[0077] 1) Weigh ranibizumab, dextran and PEG (1:5:40) and dissolve in deionized water, vortex and then freeze-dry; the powder obtained after freeze-drying is centrifuged with dichloromethane to remove the PEG dispersed phase, Vacuum drying to obtain ranibizumab-dextran microparticles;

[0078] 2) Dissolve PLGA and PCADK in dichloromethane, add the prepared p...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle diameteraaaaaaaaaa
Login to View More

Abstract

The present invention provides microspheres for intravitreal injection with double protection against antibody drugs and a preparation method thereof. The microspheres of monoclonal antibody drugs are prepared by emulsification of the water phase-water phase, and polylactic acid-glycolic acid copolymer and polyketal are used as carrier materials. Sustained-release microspheres that encapsulate and carry dextran-monoclonal antibody drug particles are prepared by the emulsification solvent evaporation method of water-in-oil-in-solid-phase. The denaturation and aggregation of antibodies caused by the acidic microenvironment of polylactic acid-glycolic acid during the organic phase / aqueous phase interface and degradation process can increase the drug loading of microspheres and reduce the burst release phenomenon during the release process of microspheres. Double protection of monoclonal antibody drugs; polyketal increases the drug loading capacity of microspheres, reduces the irritation of acidic degradation products of polylactic-glycolic acid to the eye environment, and reduces side effects such as endophthalmitis. The monoclonal antibody can be released slowly for no less than 28 days, and in the eye for no less than 2 months, which can reduce the frequency of administration, thereby reducing the pain and economic burden of patients and improving patient compliance.

Description

technical field [0001] The invention relates to a microsphere injected into the vitreous with double protection against antibody drugs. The invention further provides a preparation method thereof, which belongs to the technical field of medicine. Background technique [0002] Retinal diseases have become the second leading cause of blindness after cataract in my country, among which age-related macular degeneration (AMD) is recognized as one of the most difficult eye diseases to treat, and choroidal neovascularization (CNV) is the most important cause of vision loss. reason. Among them, vascular endothelial growth factor (VEGF) and its receptor play an important role in the proliferation and repair of pathological neovascularization. Abnormal angiogenesis causes vascular leakage in ocular vascular disease. Therefore, anti-VEGF drugs become the key to the treatment of wet age-related macular degeneration. [0003] Aflibercept (Eylea®) is the world's first fully humanized fu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/52A61K47/34A61K39/395A61P27/02
CPCA61K9/0019A61K9/0048A61K9/5031A61K9/5089A61K39/395A61P27/02
Inventor 李又欣刘佳欣孙凤英李爽滕乐生
Owner 南京锐利施生物技术有限公司