Biomedical Polymer - Poly Asparagine And Its Derivatives, Synthesis, Characterization And Bonding Of Drug Research

The important role that biodegradable poly-aspartamide and its derivatives could play as carriers in drug controlled release system has been recognized due to excellent bioactivity and especial physical梒hemical properties. Although major advances have been achieved, there are numerous limitations remaining to the scope of its application as carrier due to slower rate of degradation. It is vety meaningful to modify the structure of aspartamide, to study on the process of degradability, absorption and metabolism of the polymer and to conjugate drugs to the polymer. The objective of this thesis is to explore new polymeric materials for poly-amino acid controlled release system. Main contents of five different but related parts, that is, synthesis, characterization and degradation of novel poly-asparamide are listed below. 1 Poly- a, ~ -(hydroxyalkyl)-DL-aspartantide (PHAA) were synthesized by the ring-opening reaction of polvsuccininde (PSi) and hydroxyalkyl including hydroxyethyl, hydroxypropyl and hydroxybutyl. IR, 1H?NMR and 13CNMR confirmed the polymer structure. Mark-Houwink coefficients of PHPA were obtained from viscometiy and GPC measurements. [? ]~=5.S3 X 103M078 The effect of pH, temperature, humidity and light on the stability of PHAA were investigated. It is found that in the range of pH 3-10, the buffer solution of polymer is stable, but in acid or base, it shows some degree of degradation, especially at p1-112. As temperature increased from 25 to 80C, the molecular weight of PHAA increased. Furthermore, humidity and light had no remarkable effect on the molecular weight of PHAA under the experiment conditions. Aspirin, norethindrone, as model drugs, were covalent bounded to P1-IAA. In? vitro and in-vivo release tests were carried out. The results showed that the length of spacers was an important factor affecting the rate of release, the longer of the spacer in polymer, the faster the rate of drug release. 2 A series of functional polymers with different spacers of aspartamide were synthesized by different molar ratio of aminopropane and propylamine, (9:1,8:2,7:3,6:4,5:5). These polymers were characterized by IR, ~L{NMR, ?CNMR, OSC,XRD, and their structure were confirmed. Water sorption test of the polymer showed hydrophilicity have changed content of propylaniine. Lk- V Aspirin as model drug was conjugated into the polymers. In-viva and in-vitro release tests revealed that hydrophobicity and hydrophilicity of side-chain in the polymer effected on the rate of drug release. 3 A aeries of copolymer (PH PAA) including poly-aspartic acidl2-amino ethanoic acid, poly-aspartic acidl4-aminobutanoic acid, poly-aspartic acidlglutamic acid,poly-aspartic acid /valine acid were syntheiszed by acid-catalysis method and characterized by IR, 慔NMR, 13CNMR, DSC and XRD. Naproxen, Diflunisal, I...