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ziv-aflibercept in macular disease - clear polycarbonate

by:Cailong     2019-07-22
ziv-aflibercept in macular disease  -  clear polycarbonate
Aflibercept is an approved method of age treatment for new blood vessels
Related amd (AMD)
Diabetic edema (DME).
In vitro and in vivo studies did not detect toxicity to retinal pigment epithelial cells using approved cancer protein ziv-aflibercept.
Our purpose is to determine the ziv-
Aflibercept can be used for AMD and DME, no eye toxicity, for testing the stability of ziv-
Cost analysis was done.
Methods consecutive patients with AMD or DME combined with poor vision were treated with in-vivo injection of 0.
05 mL of fresh filter ziv-aflibercept (1. 25u2005mg).
Monitoring of best
1 day and 1 week after injection, corrected vision, intraocular pressure inflammation, cataract progression and retina structure were performed by spectral domain optical coherence tomography. Ziv-
The activity of aflibercept after 4 weeks was measured by ELISA capture of vascular endothelial growth factor.
Results AMD 4 eyes and DME 2 eyes showed no signs of retinal toxicity, intraocular inflammation or changes in crystal state.
Improved vision (p=0. 05)
Decrease in the thickness of all patients (p=0. 05). Ziv-
Aprecip has not lost its reaction.
The activity of vascular endothelial growth factor was maintained in the pc syringe for more than 4 weeks at 4 °c.
Similar to monoclonal antibody, compound ziv-
Aflibercept will generate huge savings while aflibercept or raniblizumab. Conclusion:
Label Use of Ziv-
Aprecip improves vision without eye toxicity and may offer a cheaper alternative to the same molecule aprecip.
Trial registration number nct02173873.
Background/purpose abposip is an approved treatment for age of new blood vessels
Related amd (AMD)
Diabetic edema (DME).
In vitro and in vivo studies did not detect toxicity to retinal pigment epithelial cells using approved cancer protein ziv-aflibercept.
Our purpose is to determine the ziv-
Aflibercept can be used for AMD and DME, no eye toxicity, for testing the stability of ziv-
Cost analysis was done.
Methods consecutive patients with AMD or DME combined with poor vision were treated with in-vivo injection of 0.
05 mL of fresh filter ziv-aflibercept (1. 25u2005mg).
Monitoring of best
1 day and 1 week after injection, corrected vision, intraocular pressure inflammation, cataract progression and retina structure were performed by spectral domain optical coherence tomography. Ziv-
The activity of aflibercept after 4 weeks was measured by ELISA capture of vascular endothelial growth factor.
Results AMD 4 eyes and DME 2 eyes showed no signs of retinal toxicity, intraocular inflammation or changes in crystal state.
Improved vision (p=0. 05)
Decrease in the thickness of all patients (p=0. 05). Ziv-
Aprecip has not lost its reaction.
The activity of vascular endothelial growth factor was maintained in the pc syringe for more than 4 weeks at 4 °c.
Similar to monoclonal antibody, compound ziv-
Aflibercept will generate huge savings while aflibercept or raniblizumab. Conclusion:
Label Use of Ziv-
Aprecip improves vision without eye toxicity and may offer a cheaper alternative to the same molecule aprecip.
Trial registration number nct02173873.
Introdutionaflibercept (Eylea;
Regeneron, Tarrytown, New York, USA, Bayer HealthCare, Bayer, Germany)
Is a fusion protein composed of the Fc part of human immunoglobulin IgG1 and the extracellular region of the vascular endothelial growth factor receptor (VEGFR-2 and VEGFR-1)
Circulating vascular endothelial growth factor (VEGF)
So act as a bait receptor.
Laboratory studies and clinical trials have shown that a high binding affinity for vascular endothelial growth factor in abbassipp may lead to higher activity persistence and
Aflibercept is approved by the US Food and Drug Administration (FDA)
Treatment for wet age-
Related amd (AMD)
, Retinal edema caused by retinal vein obstruction or diabetes.
Ranibizumab is administered 3 times a month, while aflibercept is administered once a month after 3 injections per month in wet AMD eyes.
Due to the high cost of raniblizumab and aflibercept, most eye doctors around the world tend to treat patients with bevacizumab4, 5, which is a big savings for patients.
In business, a fusion protein that is the same but cheaper as abrecip is ziv-aflibercept. Ziv-aflibercept (Zaltrap in Sanofi
Aventis US, LLC, Bridgewater, New Jersey, United States and Regeneron Pharmaceutical Company, Tarrytown, New York, United States)
Approved by the FDA in August 2012 for the treatment of metastatic colorectal cancer against loplatinum
Contains a plan.
People may doubt ziv-
In some retinal diseases, abasep can replace abasep.
Therefore, some major safety questions need to be answered: The first is the difference in penetration concentration and the second is ziv-
Aprecip can damage the function of the retina and change the morphology of the retina.
6 preliminary study on the use of ziv
Aprecip in patients with oozing AMD or diabetic edema (DME)
Poor eyesight.
In addition, we tested the stability of ziv-
Aflibercept in 4 weeks and the economic impact of the use of the compound. MethodsZiv-
Abashipu is available in single
Use vials of 4 mL mg per 100 and 8 mL mg per 200 mg to prepare for 25 mg ziv-
Abashipu in polyester Ester 20 (0. 1%)
Sodium chloride (100u2005mM)
Sodium citrate (5u2005mM)
Phosphate (5u2005mM)and sucrose (20%)
In the water injected with USP, the pH is 6. 2.
Eylea as a single supply
Use glass vials designed to provide 0. 05u2005mL (2u2005mg)
Abashipu (
40 mg/mL 10 mM sodium phosphate, 40 mM sodium chloride, month.
03% polyester 20, sucrose 5%, pH 6. 2). We injected 0. 05u2005mL (1. 25u2005mg)of ziv-
Aflibercept fresh (within hours)
From a new 4 ml vial.
This is 1 ml BD syringe and Luer under the hood-
Transparent polycarbonate barrel (Lok tip)
Sparks beckerton Dickinson, Maryland, USA)
And filter needles.
Fresh vials are punctured once, stored in the refrigerator at 4 °c, using the drug within a few hours of preparation
After local anesthesia and polyvidone iodine solution are dripping, a sterile eyelid retractor is placed.
Drug injection 3.
The distance from limbus to mid is 5mmGlass cavity.
Using the Snellen chart, the same examiner monitored best corrected vision 15 minutes, 1 day and 1 week after the injection.
Optical coherent tomography (OCT)
Performed before and after 1 week of injection to find possible side effects of using a high dose drug
Resolution scan from RTVue-100 (software V. 6.
7, Optovue, Inc. , Fremont, California, United States of America).
Central retina thickness (CMT)
Determined by the same independent operator on the same machine.
By mean horizontal and vertical measurements, the height of the skin detachment of the retina pigment was measured on horizontal and vertical scans.
Inclusion criteria include eyes with active newborn vessels AMD or DME, best-
Corrected vision 20/100 (6/30)
Or less, the ability to understand the risks and benefits of learning, the ability to sign a formal consent form.
The exclusion criteria included signs of eye infection, use of previous eye Zhou or intraocular cortical steroids, previous resistance
In the past 3 months, vascular endothelial growth factor has been treated with a history of stroke or myocardial infarction.
Statistical analysis is the use of non-
Parameter Wilcoxon symbol-Ranks test.
The research programme was approved by the Institutional Review Committee in May 2014.
The study has been registered (
NCT02173873 clinical data obtained using spss v analysis. 20. 0 (
IBM/SPSS Inc. , Chicago, Illinois, United States of America).
Analysis with paired sample t Test 1-
Weekly results and baseline values for vision and CMT.
In vitro ELISA detection of vascular endothelial growth factor combined with ziv
Okay, okay, okay. Okay, okay-
The meter 5 μ BD filter is 1 mu ml BD Luer-
Syringe with polyester barrel (
Benton, Dickinson, Franklin Lake, New Jersey, United States of America)
Syringe, refrigerate for 2 weeks and 4 weeks at 4 °c.
A fresh bottle of ziv
The aprecip was used for control and reference.
Fvi5, the restructuring person we use (rhVEGF)(cat no. 293-VE-
010, R & D system, Minneapolis, Minnesota, United States)
Human vascular endothelial growth factor ELISA kit (cat no.
DVE00 R & D system).
Ziv at different concentrations-
Sample (10–10u2005mg/mL)stored were co-
Incubation of rhvascular growth factor (100u2005ng/mL)
Dilute with phosphateBuffer salt water. The ziv-aflibercept-Rhvascular growth factor complex200 μl per hole)
Incubation was performed at room temperature for 30 min and residual rh vascular endothelial growth factor was determined.
ELISA plates were incubated with stirring at room temperature for 3 h.
Then wash the plate with phosphate
The unbonded complex is removed by buffered saline.
An anti-vascular endothelial growth factor (biotin-conjugated)
Then added to the well.
After washing and removing the unbound antibody, the reagent is detected (streptavidin-
Hydrogen peroxide)
Add to combine biotin-
Mark the antibody.
The plate is washed, the substrate solution (3,3′,5,5′-
4-methyl benzidine/hydrogen peroxide)was then added.
The last stop Solution (sulfuric acid)
Increased optical density (A450 and A550)
Read using a splitter.
In vitro ELISA detection of vascular endothelial growth factor combined with ziv
Okay, okay, okay. Okay, okay-
The meter 5 μ BD filter is 1 mu ml BD Luer-
Syringe with polyester barrel (
Benton, Dickinson, Franklin Lake, New Jersey, United States of America)
Syringe, refrigerate for 2 weeks and 4 weeks at 4 °c.
A fresh bottle of ziv
The aprecip was used for control and reference.
Fvi5, the restructuring person we use (rhVEGF)(cat no. 293-VE-
010, R & D system, Minneapolis, Minnesota, United States)
Human vascular endothelial growth factor ELISA kit (cat no.
DVE00 R & D system).
Ziv at different concentrations-
Sample (10–10u2005mg/mL)stored were co-
Incubation of rhvascular growth factor (100u2005ng/mL)
Dilute with phosphateBuffer salt water. The ziv-aflibercept-Rhvascular growth factor complex200 μl per hole)
Incubation was performed at room temperature for 30 min and residual rh vascular endothelial growth factor was determined.
ELISA plates were incubated with stirring at room temperature for 3 h.
Then wash the plate with phosphate
The unbonded complex is removed by buffered saline.
An anti-vascular endothelial growth factor (biotin-conjugated)
Then added to the well.
After washing and removing the unbound antibody, the reagent is detected (streptavidin-
Hydrogen peroxide)
Add to combine biotin-
Mark the antibody.
The plate is washed, the substrate solution (3,3′,5,5′-
4-methyl benzidine/hydrogen peroxide)was then added.
The last stop Solution (sulfuric acid)
Increased optical density (A450 and A550)
Read using a splitter.
Results four consecutive wet AMD patients and two DME patients received a glass in vivo injection of ziv-
Abashipu was put in one eye (table 1).
View this table: View clinical data for ziv
These patients cannot afford initial or additional injections of-
Actively seek compassionate diagnosis and treatment options.
All patients had increased visual acuity on the first day after surgery, with no signs of inflammation in the anterior chamber and in the glass, no retinal detachment or retinal bleeding.
There is no progression of cataract or posterior SAC turbidity.
Intraocular pressure was not monitored.
10 minutes after the injection, we only checked the vision and in all cases the vision was equal to the pre-injection level.
Of the four AMD patients, the height of foveolar detachment of the retinal pigment epithelial in four patients decreased from an average of 583 μA to a final average of 398 μ 1 a week after injection.
Combined with the results of six cases, the average value (SD)
The initial vision of LogMAR was 1. 40 (0. 36)
0 in 1 week. 86 (0. 17)(p=0. 05).
Similarly, the average value of the initial CMT is 482 μm (217u2005µ)
And down to 345 mu u in 1 week (111u2005µ)(p=0. 05).
Original Vial concentration of Ziv-
Aflibercept is 25 mg/mL (
In the current study)
This is consistent with the known dose of treatment (10–40u2005mg/mL)
For Amber.
So we chose the highest concentration of 10 mg/ml.
Stability of Ziv
Abasip assessed its efficiency in capturing rh Vascular Endothelial Growth Factors by measuring the concentration of free vascular endothelial growth factors unrelated to the complex.
Ziv-10 mg/ml
During the whole test, afliberbound combined 90% of rhvascular growth and this combination was stable (4u2005weeks).
However, at a lower concentration of ziv-aflibercept.
At 10 μg/mL, ziv-
Aflibercept binds 60% to rhvascular growth, which was reduced to 45% and 25% respectively after 2 weeks and 4 weeks (table 2).
View this table: View inline View pop-up table 2 vascular endothelial growth factor (VEGF)
Binding capability with ziv-
Using this low concentration for 28 days, we show the ability of ziv
Aprecip captures free vascular endothelial growth factor in a clinical setting. Ziv-
At a concentration higher than 100 μg/mL, abasip stabilized for 4 weeks at 4 °c (
Know that the concentration of the drug is expected to be around 1 at the time of injection.
25 mg/4 mL or 300 ml in the glass body).
Ziv's projected composite cost is reduced by 20 times
If 4 ml ziv-
The small bottle of aprecip is divided into 40 equal points (table 3).
View this table: View inline View popupable3 comparison
Vascular endothelial growth factor (anti-VEGF)
In the first year of wet AMDThis treatment, drugs with approved protocols and costs for related drug treatments can be achieved in two ways: as suggested by Ng et al, 7 Chen et al and Ornek et al, puncture the vial directly for each patient, 9 or split by the compound pharmacy due to the excellent stability of the drug.
There are two reasons for economic differences after one year of treatment.
First, use a separate or composite ziv-aflibercept;
Second, a less intensive dosing regimen using zivaflibercept (8 doses of Ziv
Aprecip or aprecip vs 12 for relizumab or beavumab)(table 3).
Discussion of the molecular weight of abrecip is 15-, which is made by Chinese hamster ovarian cells.
Abasip is structurally the same as anti-cancer drug zivaflibercept;
However, it goes through different purification processes and contains different buffer solutions that are less irritating when injected into the glass body. 6 Since ziv-
Aflibercept has the same molecular structure as aflibercept and we decided to try ziv-aflibercept (0. 125u2005mg)
Its concentration is reduced compared to the abrecip (2u2005mg).
Aflibercept comes with different
Penetration solution (300u2005mOsm/kg), while ziv-
The osmosis pressure of Aflibercept is 1000 u2005 mOsm/kg.
Marmor et al found in rabbits and primates that a solution less than 500 mosm did not cause damage to the retinal pigment epithelial.
The tension between 500 and 1000 momosm creates an inconsistency, usually only partially damaged.
The injection of more than 2000 momosm quickly resulted in severe changes in the retinal pigment epithelial cells, loss of fluff and detachment of the retina.
The average size of rabbit eyes is 1.
The volume of primate mesh is from 1. 5 to 2.
0 ml, while the human eye volume is from 4. 0 to 6. 0u2005mL.
The volume injected in these experiments is 0. 05u2005mL.
Because the human eye is about three times larger than the rabbit, the human eye will theoretically endure more high penetration injections than the rabbit's eyes, so the threshold of penetration concentration in humans is higher.
There are no signs of toxicity in 1000 mommosm/kg ziv-
The aprecip injection group is associated with a small number of drugs injected that do not result in a significant change in the total penetration concentration in the glass body. Diluting 0.
05 mL drug entry into the glass body 4 ml represents 80 times dilution, So 1000 momosm/kg solution will be diluted after injection in the glass body (
The calculated final penetration concentration of the original 300 momosm/kg to 312 momosm/kg or an increase of 4%;
(Within the physiological range)
Does not affect the retina. 11 ,12 Ziv-
Aprecip needs to be injected into the medium term
As a precaution, the glass cavity and away from the lens.
Laboratory studies show the relative safety of ziv-
Aprecip in animal eyes and cell preparation.
In a study by Malik et al, 13 human retinal pigment epithelial cells were exposed for 24 hours to 4 Antibodies
Administration was given at clinical concentrations of 1/2 times, 1 times, 2 times, and 10 times.
Cell viability and mitochondrial membrane potential were measured to evaluate early apoptosis changes and overall cell mortality.
At the clinical dose, no evidence of mitochondrial toxicity or cell death was found either in rezhuumab or in aprecip.
However, monoclonal antibody and ziv-
Abasip showed mild mitochondrial toxicity at clinically relevant doses.
In another study by Klettner et al, 14 aflibercept has no toxicity to retinal pigment epithelial cells while damaging the swallowing capacity of these cells.
Recent data show ziv-
Abasip is safe in the eyes of rabbits. 15: 18 rabbits were injected into the glass. 05u2005mL ziv-
Either aprecip or aprecip.
As of October, all eyes were cataract and retinal detachment negative 1 day and 7 days after injection, with no anatomical signs and histological signs of toxicity.
In View 1 and View 2, patients were randomly assigned to one of the four groups: 2 mg of abrecip for each 8 weeks (
Three months after the initial dose)
, 2 mg per 4 weeks, abershipp 0.
5 mg every 4 weeks, 0 for rebead monoclonal antibody.
5 mg every 4 weeks.
The main end points of the four groups are comparable, that is, the proportion of patients who maintain vision (
Defined as missing
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