New long-term action insulin formulations obtained using polycations for heparin neutralization

2019 ◽  
Vol 15 (3) ◽  
Author(s):  
Kamil Kamiński ◽  
Marta Kaczor-Kamińska ◽  
Izabela Irska ◽  
Iwona Popiołek ◽  
Krzysztof Szczubiałka ◽  
...  

AbstractPhenomena that occur between an insulin and four different positively charged polymers (protamine, cationic dextran, chitosan, and poliallylamine derivatives) were studied by dynamic light scattering and fluorescence measurements (using fluorescein-labeled polymers). These processes were compared to the reaction of polycations with heparin that is responsible for the neutralization of anticoagulant activity in blood stream.The nature of polycations interaction with heparin is electrostatic, while the interaction with insulin is more complicated.We observed that the presence of zinc atoms (and its complexing by nitrogen from macromolecules) is critical for insulin suspensions formation and stability. The differences between the nature of these two reactions were revealed. The highly immunogenic action of protamine present in long-acting insulin products makes it reasonable to develop similar systems based on the nonprotein polycations.

2011 ◽  
Vol 879 (28) ◽  
pp. 2945-2951 ◽  
Author(s):  
Malene H. Jensen ◽  
Per-Olof Wahlund ◽  
Jes K. Jacobsen ◽  
Bente Vestergaard ◽  
Marco van de Weert ◽  
...  

2011 ◽  
Vol 236-238 ◽  
pp. 2032-2035
Author(s):  
Xiang Feng Jia ◽  
Xing Wang Shi ◽  
Yong Shan Ma

The formation of inorganic/organic Complex Material from giant polyoxomolybdate (POM) macro-anions in solutions mixed a positively charged surfactant tetradecyltrimethylammonium bromide (TTA+Br-1) was described.surfactant tetradecyltrimethylammonium bromide (TTA+Br-1) was described. The complex can further dissolve in aqueous solution with the excess TTABr and the larger hydrophilicaggregations formed. TEM and Dynamic Light Scattering (DLS) investigations were applied to analyze the aggregations in the simple-phase solution.


2012 ◽  
Vol 77 ◽  
pp. 53-58 ◽  
Author(s):  
Olga Pavlova-Verevkina ◽  
Natalia Golubko ◽  
Alexander Sumbatov ◽  
Ludmila Ozerina

The long-term stability of two TiO2 hydrosols with concentration of TiO2 nanoparticles 1 and 12 mass.% was compared by turbidimetry and dynamic light scattering. The both sols were stabilized by HCl at pH=0.5. It was found that the mean hydrodynamic radius of particles and the turbidity of the sols increased slowly for six months of investigation and the kinetics of the “ageing” of the sols did not depend on TiO2 concentration. The obtained results will enable to determine mechanisms of the slow growth of nanoparticles and to modify nanoparticles structure.


2017 ◽  
Vol 35 (32) ◽  
pp. 3647-3653 ◽  
Author(s):  
Jennifer W. Wu ◽  
Laurent Azoulay ◽  
Agnieszka Majdan ◽  
Jean-François Boivin ◽  
Michael Pollak ◽  
...  

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom’s Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.


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