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1.
Acta Pharmaceutica Sinica B ; (6): 2719-2725, 2021.
Article in English | WPRIM | ID: wpr-888883

ABSTRACT

Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes. These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity. New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin. Herein, we report a new method using sortase A (SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain. This new insulin molecule (Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives. We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and

2.
Acta Pharmaceutica Sinica B ; (6): 34-50, 2018.
Article in English | WPRIM | ID: wpr-771138

ABSTRACT

Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

3.
Clinical Medicine of China ; (12): 209-214, 2018.
Article in Chinese | WPRIM | ID: wpr-706653

ABSTRACT

Objective To explore the efficacy and safety of Bevacizumab combined with albumin binding paclitaxel in the treatment of platinum resistant recurrent ovarian cancer.Methods From June 2014 to January 2016,eighty-two recurrent ovarian cancer patients were selected in the study and randomly divided into the treatment group (41 cases) and the control group (41 cases),the control group was treated with albumin binding paclitaxel,and the treatment group was treated with Bevacizumab combined with albumin binding paclitaxel.The clinical efficacy (such as overall response rate,complete response rate,partial response rate,stability of disease,progression of disease),progression free survival (PFS),overall survival (OS) and the adverse reaction rate were compared.Results The total effective rate (ORR) of the experimental group was 85.37% (35/41),which was significantly higher than that of the control group (65.85% (27/41),and the difference was statistically significant (P=0.040).The median PFS and OS in the experimental group were 9 (1 ~16) months and 16 (4~26) months,significantly higher than those in the control group (6 (1 ~ 13)months (HR =0.624,95% CI:0.367 ~ 0.899,P =0.023);12 (2 ~ 25) months (HR =0.603,95% CI:0.324 ~ 0.791,P =0.009);subgroup analysis showed that the median OS of patienta without metastasis in the experimental and control group were 18 (8 ~ 26) months and 13 (2 ~ 25) months respectively (HR =HR =0.610,95% CI:0.229 ~ 1.544,P=0.291),and the median PFS was 11 (5~ 16) months and 8 (1 ~ 13) months (HR=0.496,95%CI:0.160~1.046,P=0.089),there were no significant differences;the median P FS in patients with metastasis of the experimental group and the control group were 9 (3~14)months and 6 (1~ 10)months (HR =0.483,95% CI:0.273 ~ 0.769 months,P<0.001),the median OS were 14 (4~22) months and 11 (2~20)months (HR =0.556,95%CI:0.197~ 0.569,P=0.008).There was no significant difference in the incidence of adverse reactions between the two groups (12.20%,21.95%,P=0.240).Conclusion Compared with the treatment of albumin binding paclitaxel,in the treatment of platinum resistant recurrent ovarian cancer,the combined treatment of bevacizumab and albumin binding paclitaxel can significantly improve the clinical effect and improve the patients' survival and total survival time.

4.
Neonatal Medicine ; : 268-275, 2013.
Article in Korean | WPRIM | ID: wpr-97620

ABSTRACT

During the last 30 years, there has been much advances in the understanding of pathogenisis of neonatal hyperbilirubinemia, but the risk of bilirubin encephalopathy are still remained for the high risk neonates. The mechanisms of bilirubin encephalopathy are not thouroughly understood. Various theories may explain bilirubin transport acoss the blood-brain barrier. Free bilirubin, not bound to albumin, can enter the brain. The permeability of the blood brain barrier to bilirubin or albuimin and bilirubin binding may play an important role in the bilirubin encephalopathy. Bilirubin binding ability of Korean infants, similar to American infants, is shown to be less than that of adults. Factors influencing bilirubin-albumin binding, such as acidosis, hypoxia, sepsis, hypothermia, hypoglycemia and immaturity should be considered for neonates at high risk of bilirubin encephalopathy. Free bilirubin is found to be significantly increased in preterm infants with low albumin level. Sulfisoxazole inhibits the bilirubin-albumin binding that resulted in increased free bilirubin concentrations even at low total bilirubin levels. Phenobarbital has no effects on bilirubin binding capacity of albumin. Phototherapy for 48 hours has no influence on bilirubin-albumin binding capacitiy and affinity. Auditory evoked repsonse (ABR) changes in the form of I, III, and IV wave reduction are associated with brainstem and cerebellum bilirubin deposition. Since early detection of bilirubin neurotoxicity is promising for improving outcome for high risk neonates, ABR and other electrophysiological measure will be useful.


Subject(s)
Adult , Humans , Infant , Infant, Newborn , Acidosis , Hypoxia , Bilirubin , Blood-Brain Barrier , Brain , Brain Stem , Cerebellum , Hyperbilirubinemia, Neonatal , Hypoglycemia , Hypothermia , Infant, Premature , Kernicterus , Permeability , Phenobarbital , Phototherapy , Sepsis , Sulfisoxazole
5.
Chinese Journal of Diabetes ; (12)2008.
Article in Chinese | WPRIM | ID: wpr-593224

ABSTRACT

Objective To compare the ischemia-modified albumin(IMA)level between T2DM and AMI,and to discuss the possible mechanism and pathology process.Methods According to the decrease of power of albumin binding cobalt along with the increase of ischemia-modified albumin,the automated continuous detection of free cobalt in reactive system were conducted using the 480nm wavelength and the results were reported as absorbance unit(ABSU)and coloration rate of free cobalt.Results There were significant differences in serum free cobalt between the control and groups of acute coronary syndrome(ACS)and type 2 diabetes and between ACS and type 2 diabetes(P

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