Author name:
رنا نعمة عطية
Supervisor name:
ماجد جاري محمد | نغم محمود الجمالي
University location:
Najaf
Abstract:
تضمن هذا البحث تحضير سلسلة انواع جديدة من البولي يوريثين المتفكك احيائيا والحساس لــلدالة الحامضية والذي يحتوي على مشتقات البنزوكائين المتضمنة مجموعة الازو بالبلمرة التكاثفية لـ 1,6 - hexamethylene diisocyanate في درجة حرارة 80 م مع مونمرات الازو، كيميائ | In this work series of new types of biodegradable and pH - sensitive polyurethane containing azo derivatives of benzocaine were synthesized by the condensation polymerization of 1,6 - hexamethylene diisocyanate at 80 ?C with the azo monomers. The chemically controlled release methods have been applied in which the benzocaine (drug) with active group (NH2) linked up with the spacer group (dihydroxy monomers) by azo bond formation.The First stage : The monomers synthesized from the reaction of (cyclohexanone , 1 - naphthole, 2 - naphthole , 4 - bromophenol , 3 - chlorophenol , phenol , 4 - (2,4 - dihydroxyphenyl)but - 3 - en - 2 - one , 4 - (4 - hydroxyphenyl)but - 3 - en - 2 - one and p - hydroxy acetophenone ) with acetone in presence of HCl as catalyst under reflux condition. M1 M2 M3 M4 M5 M6 M7 M8 M9The Second stage : The azo monomers were synthesized from the reaction of monomers : (M1 ,M2 ,M3 ,M4 ,M5 ,M6 ,M7 ,M8 ,M9 ,hydroquinone ,pyragollal ) with Benzocaine in presence of HCl , NaNO2 and NaOH 10% by stirring for one hour in ice bath at (0 - 5 ?C). AZO1 AZO2 AZO3 AZO4 AZO5 AZO6 AZO7 AZO8 AZO9 AZO10 AZO11 Where (R) : is the above monomers which shown in first and second stage.The Third stage : polyurethane azo was synthesized from the reaction between the azo monomers (which are shows in second stage) with 1,6 - hexamethylene diisocyanate in oil bath by refluxing for 8 hours at 80 ?C in dry nitrogene.where : ( R ) are the monomers which shown in first and second stage.The U.V - Visible , FT - IR , H1NMR techniques were used to confirm the chemical structure of the synthesized Polyurethane azo.A calibration curve between absorbance and concentration was constructed to stock solution of pure drug. the concentration of Benzocaine release was calculated by extrapolation of the result on the calibration curve every 24 hrs. The detection limit for Benzocaine was minimum used 0.001 gm/mol wavelength at 293 nm. Benzocaine was loaded into the polymeric matrix during in situ polymerization. The drug release from the benzocaine loaded was studied in two different medias ( pH=7.8, pH=4 ) at the human temperature.The results was shown that degradation of polyurethane azo in phosphate buffer solution was dependant in the pH value. In pH7.8 the polyurethane azo was rapidly released over 45 hrs. Incubation of polyurethane azo with rate cecal content at 37 ?C gradually released of benzocaine and the percentage of drug released was follow sequence (57% ,82% , 84% , 73% , 73% , 78% , 80% , 82% , 79% , 75% , 86% ) in 45 hrs. In pH=4 polyurethane azo was released slower than basic condition over 45 hrs. at 37 C, and the percentage of drug release was follow sequence (49% , 76% , 72% , 49% , 68% , 60% , 66% , 77% , 70% , 66% , 60%).The release rate of Benzocaine increased with increasing pH (i.e. , 7.8?4).
