Modification of some Polymers or Riboflavin with Black Seed - PowerPoint Presentation

1. Modification of some Polymers or Riboflavin with Black Seed(Nigella sativa) Components*Firyal M.A. , Enas M.N. , Falah H.H. , Riyadh M. N. , Shuaa S.H.& Zainab K.A.*Ministry of Industry & Minerals, Ibn Albetar Research Center. *Al- Mustansirya University, College of Science, Department of Chemistry

2. Summary :- In this research the modification of N.sativa fixed oil which containing Linolic , Oleic , Linolenic , Arachidic , Palmitolic , Elcosadienoic and Palmitic Acids were converted to their acid chlorides by thionyl chloride , these acid chlorides of fatty acids were reaeted with chitosan as drug carrier polymer , or with vitamin B2 to obtain drug carrier vitamin as new derivatives . The copolymerization of acrylic acid with N.sativa through unsaturated groups gave a good copolymer , All prepared compounds were charaeterized by FTIR , UV and H – NMR. and thermal analysis such as DTA and TGA were studied . The prepared compounds were studied by microsccope images , Controlled release were measured in different pH values at 37˚C , This technique through targeting can be achieved as timed released system in specific site producing nontoxic natural materrals such as essential oils because they can not be synthesized by human body with them carriers such as chitosan as poly saccharide , or vitamin B2 as useful materials with suitable concentrations .the novel compounds were prepared with best application results were developed with high improvement as drug polymer.Key words : Nigella sativa , Vitamin B2 , Copolymer

3. Experimental Materials and Instruments Riboflavin and chitosan were purchased from BDH,All chemical materials were used without further purification . UV. Spectra were recorded by a Shimazu UV – vis , FTIR spectra were recorded by a shimatzu spectrophotometer in range 4000 – 400 cm-1 . Thermo gravimetric analysis was carried out on a Shimatzu 60 instruments ( Japan ) .Microscops W/Two Lights + 3M camera , Model ME 300 TZ – 2L – 3M .H – NMR spectra were recorded by a Brucker AC 500 spectrometer using DMSO as a solvent .Extraction of Nigella sativa

4. Extraction of Nigella sativa Seeds of N.sativa were purchased from Local market 50 g . were cruched and extracted with petroleum ether for 15 hrs , in soxhlet apparatus . The extracted was concentrated under reduced presure and the fixed oil was obtained with 25% ( 32 , 33 ).Synthesis of acid chloride derivatives of Nigella Sativa compositions The acids of fixed oil of Nigella sativa were refluxed with excess thionyl chloride for 1hr on a water bath , then the excess of thionyl chloride was distilled off .Then the product was distilled under reduced pressure and kept under nitroyen , at atmosphere pressure

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6. Modification of chitosan with N.sativa fixed oil C1 ( 3g , 0.018 mole ) of chitosan was solubilized in 5ml of 1% of acetic acid and (2g , 0.018 mole ) of prepared fatty acid chlorides was added drop wise with vigorously stirred at 0˚C about 2 hrs . The reaction mixture was heated at 40˚C for 1 hr , the modified polymer was formed , washed with 5 % sodium bicarbonat , dried at 50˚C in a vacuum oven .

7. Esterification of vitamin B2 ( Riboflavin ) with N.sativa C2 ( 2.4g , 0.01 mole ) of vitamin B2 was solublized in 10ml of DMF and ( 1.8g , 0.01mole ) of fatty acid chlorides of N.sativa was added gradvally at room temperature in the presence of triethyl amine with stirring , The mixture was refluxed about 3hrs . The high yellowish product was isolated and washed with ethanol then dried . The physical properties were listed in Table ( 3 ).

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9. Copolymerication of N.stiva with acrylic acid C3 To a screw – capped polymerization bottle containing 2g of acrylic acid and 2g of unsaturated fatty acids of N.sativa , the 8ml of dioxan was used as a solvent , 0.05g ( 0.025 % by weight of the monomers concentration ) of dibenzoylperoxide, the clear solution was flushed with nitrogen gas, the bottle was then closed and incubated in a water bath at 90˚C for 1hr . The mixture was cooled and the contents were poured into a beaker of methanol . A white viscous preciptate was formed wich coagulated when warmed .The prepared copolymer was separated and dried in a vacuum oven . The yield of polymer was 80% , The physical properties are listed in Table ( 4 ).

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11. Viscosity measurments Ubbelhode , capillary viscomater was used to determined of viscosities of the prepared polymer at 25˚C . and the relative , spesific , reduced and intrinsic viscosities were calculated from the intercept of graph by plotting µred Vs C% ( 34 ) .Controlled release study According to procedur [ 35 ] with some modification . A 100mg of modified polymer was kept in a cylinder containing of 100ml of buffer solution at 37˚C without stirring . The sample was periodically withdrawn and analyzed by UV. Spectroscopy at a suitable (λ max = 320 nm) for every prepared sample to determined the amount of the released fixed oil of N.sativa fatty acids , directly from the softwere built for many times using different pH values

12. Result and Discussion Chitosan is a natural polymer poly succharide which is available , sustainablty renewable , and possess . Better biocompatibility , biodegradability , a low or non- toxicity and have a higher modification capability compaired to various synthetic materials , these due to containing NH2 groups which could substituted by fatty acids at N.sativa , as shown in the following equation .

13. R= Linoleic , Oleic , Lenolenic , Arachidic , Palmitolic , Elecosadienoic , Palmic , Stearic , Myristic acid chlorides , The modified chitosan with N .sativa is to increase the effeciency of treatment as the concentration of active substance is regulated continuously and at more appropriate sites , and readily sustainably to avoid the initial high dose and to prevent its side effect . The white polymer has ηin = 0.76 dl / g . FTIR spectra Fig.( 1a ) of N.sativa and ( 1b ) of modified chitosan are showed disappearance of –NH2 and the stretching vibration of –NH amide at 3305cm-1 was observed, the –C = 0 of fatty acid was converted to –C =0 amide which appeared at 1707 cm-1 , this confirms the formation of amide groups of C1.The disappearance of –OH carboxylic group confirms the possibility of structural change of fatty acids of N.sativa . The latter intense peaks ( 3090 cm-1 ) is assigned to the –CH unsaturated .

14. The remained –OH of polysaccharide in chetosan was appeared at 3400 cm-1 which is overlapping with –NH absorption as a shoulder bands at 3305 cm-1 . The absorption at 2995 cm-1 is ascribed to the –CH aliphatic .The modified percentage was 60% of –NH2 % which was calculated by titration of modified chitosane with 0.1 N of acetic acid solution by using phenol phthaline as indicater .Esterification of vitamin B2 with fatty acid chlorides was carried out through condensation of hydroxy groups of vitamin B2 with acid chlorides in the presence of triethylamine as a catalyst as illustrated in the following equation :-

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16. Fig ( 2 ) shows the FTIR spectra which confirmed the formation of ester group of C2 appeared at 1742 cm-1 was due to the conjugated ester carbonyl stretching of ester group . The a symmetry stretching vibration of methylene group was observed at 2962 cm-1 . The adsorption peak of double bond at ( 1620 – 1680) cm-1 was observed for vitamin B2, some of OH groups remined at 3450 cm-1 .Fig (3) FTIR spectrum of prepared acrylic – N.sativa copolymer shows the appearance of OH carboxylic at ( 3450 – 3000 cm-1 ) and abroad absorption due to acrylic acid and fatty acids , the disappearance of C C at ( 1656 cm-1) and the absorption at ( 1720 cm-1) was observed due to C O carboxylic acid of copolymer C3 .Fig (4) shows the microscopy micrograph of prepared polymer C1 , it can seen that the graph shows dual continuous phase , therefore the sample with L= 157.21 d=5.22 exhibit the characteristic of thermoplastic elastomeric , which is clearly evident from the continuous phase morphology with respect to Fig (5) of sample C3 which has L= 7.024 , d=0.79 , shows the finest grain morphology .i.e. , the size of grain morphology can be given in the order sample C3 higher than sample C1 this is attributed to chemical interaction at the interfaces of polymer layers caused by polar functional groups .

17. The modification of Riboflavin with N.sativa fatty acid chlorides were esterified with hydroxyl groups of vitamin B2 to produce N.sative vitamin carrier to increase the advantages of two useful compounds with prolong time the materials with controlled release by hydrolysis the ester compound C3 in different pH values as shown in the following scheme (1) :-

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19. The aim of this work is to enhanced the sustained delivery system through chemical bond and slowly released under appropriats medium condition of human body to minimize the toxicity of the N.sativa with suitable sustained doses ( 36,37 ) . Fig (10) showed the UV. spectra of controlled release in pH (7.4) which were observed a high rate of hydrolysis, this attributed to -OH attack on carbon atom of C O ester of C2 as illustrated in scheme (1). It was concluded from these study the vitamin ester could hydrolysis as sustained rate in basic medium to minimize the side effect of the dosage of N.sativa .Fig (7) TGA and Fig (8) DTA were indicated the thermo plastic properties of prepared acrylic – N.sativa copolymer ranged in ( 210 – 220 °C ) with weight loss about ( 50 – 55% ) .This indicated the thermal stability of the prepared new drug compound.Fig (8) shows the area ( 40.49 µVs/mg ) at ( 30.8 °C ) as endothermic appeared after ( 0.03 min ) was exothermic appeared ( - 126.93 µV s/mg ) at ( 144.9 °C ) was observed at ( 14 min ) . The third area was observed ( 3.28 µV s/mg ) at ( 204.9 °C ) after ( 18 min ). The fourth large area ( - 531.23 µV s/mg ) at ( 228 °C ) appeared after ( 20 min ) as exothermic area shape .

20. Figure (11) H-NMR spectrum shows the signals of N-sativa - acrylic acid copolymers which indicated the disappearance of C=C groups in the two monomers N. sativa and acrylic acid . The signal at 1.4-2.7 ppm indicated the precence of [CH1-CH2] n of acrylic acid as doublet, triplet signal, and the signals of [CH2] m of N. sativa fatty acids .The COOH of two monomers were appeared in low field , above 13 ppm.

21. Fig (1a ) FTIR spectra of N.sative

22. Fig ( 1b ) FTIR spectra chitosan with N.sativa C1

23. Fig ( 2 ) FTIR spectra of vitamin B2 with N.sativa C2

24. Fig ( 3 ) FTIR spectra of acrylic – N.sativa copolymer C3

25. Fig ( 4 ) Microscopic graph of chitosan – N.sativa C1

26. Fig ( 5 ) Microscopic graph of vitamin B2 – N.sativa C2

27. Fig ( 6 ) Microscopic of acrylic – n.sativa copolymer C3

28. Fig (7) TGA of acrylic – N.sativa copolymer

29. Fig (8) DTA of acrylic – N.sativa copolymer

30. Fig(9)Controlled release of N.sativa C2 in pH7.4

31. Fig (10) UV.spectra of Controlled release of N.sativa in different pH 7.4 at 37°C for C2 

32. Fig (11) H-NMR spectrum of N. sativa –acrylic copolymers.