Nghien CLFU - Ky thuat
Cdn CLP vdo sd lidu phd dd phdn tich d trdn va so sdnh vdi sd lieu phd da duac cdng bd '"* ^', hap chit TGGT10 duge nhan dang Id a- toeopherolquinon.
Hinh 2: Ciu true hda hoc cua hap chit TGGT10
Ket luan
Tu djch chidt ethanol tim giri ky sinh tren cay gao, bing phuang phap sic ky cpt nhieu lin da phan ldp dugc 2 hgp chit, ky hieu TGGT9 vd TGGT10. Dua vdo sd lieu phd khdi lugng vd phd cdng hudng tu hat nhan mdt chidu vd hai chieu, so sdnh vdi tdi lieu da cdng bd, xdc djnh TGGT9 Id trans-phytol vd TGGT10 la G-tocopherolquinon. Ddy la cdng bd diu tidn ve hai hgp chit ndy cd trong tim giri Taxillus
chinensis (DC) Dans sdng ky sinh tren cay gao.
S u m m a r y
By various chromatography methods, trans-phytol and a-tocopherolquinone were Isolated from the ethanolic extracts of Taxillus chinensis (DC) Dans. Their chemical structures were elucidated by ESI-MS, ' H - NMR, '^C-NMR, DEPT, HMBC. HSQC. This is the first report on these compounds from Taxillus chinensis (DC) Dans.
Tai lieu tham khao
1. Bo y te: Duac dien Viet Nam IV, NXB Y hoc, (2009), Tr 887.
2. V5 Van Chi: Tir dien cay thuoc Viet Nam.A/XS Yhgc, (1997), 1100.
3. G.D.Brown: Phyton-1,2-diol from Artemisia annua. Phytochemistry. (1994), Vol 36(6) 1553-1554.
4. J. De Pascual Teresa, J. G. Drones, I. San chez Marcos, J. Fernandez, A. M. Lithgrow Bertelloni and P. Basabe Barcala., Diterpenoids from Nepeta tuberosa Subsp. Reticulata.. Phytochemistry, (1987), Vol 26 (5), 1481-1485.
5. Nazli Rasool, Abdul Qasim Khan, Viqar Uddin Ahmaed and Abdul Malik; A Benzoquinone and A coumestan from Psralea plicata. Phytochemistry, (1991), Vol 30 (8), 2800-2803.
Nghien ciru xay dyng cong thirc hon dich nano piroxicam
Dat van de
Cdng nghe nano dang din tung budc irng dung trong nganh dugc vdi nhOng thdnh cdng nhlt djnh. NhO'ng san pham bdo chd tu he nano cd nhu'ng uu diem vugt trdi ve kha nang hip thu do dde tinh be mdt vd kich thudc sieu nhd. Tuy nhien, vide duy tri nhu'ng ddc tinh uu viet ciia tidu phdn nano tuang ddi khd khdn bdi nhO'ng tidu phan kich thude cdng nhd cdng ed xu hudng de kdt tu thdnh tieu phdn Idn han de giam ndng lugng be mat tu dc nhlt Id khi dua nguyen lieu kich thudc nano vdo cdc dang bdo che cd clu true khdc nhau cung vdi su cd mdt ciia nhieu ta duge khdc'^' Hidn tugng
Nguyen Thi Mai Anh, Nguyen Van Long Trudng dgi hoc Dirac Hd Noi
nay gay anh hudng ldn ddn hieu qua dieu tri cua thudc. Piroxicam la dugc chit thupc nhdm giam dau chdng viem khdng steroid cd dae tinh it tan trong nudc vd thim kem. Vdi mong mudn lam tang hip thu piroxicam qua da, niem mac, qua tham khao mdt sd tdi lieu'^'®', chung tdi thuc hien de tdi:
'Nghien ciru xiy dwng cdng thirc hdn dich nano piroxicam".
D6i tu'O'ng, nguyen lieu, phu'O'ng phap nghien
CLPUDdi tifgng nghien ciru: piroxicam
Nguyen lieu: piroxicam (Px- Tmng Qudc), tieu
chuin USP 30, Eudragid RS 100 vd alcol polyvinie
TAP CHi DUQC HQC-7/2011 (SO 423 NAM 51)
39Nghien CLFU - Ky thuat
(PVA- Dwc). Mdt sd dung mdi, hod c h i t tinh khiet hda hpe dung chc bao che va phdn tich.
Thiet bi: May khuly Braul 4185 (See), may ly tdm Sigma 3-18 K Satorius (Diyc). kinh hien vi dien tir quet FESEM Hitachi S-4800 (Nhdt), kinh hien vi dien tir truydn qua JEM 1010 (JOEL), may xac dinh phdn bd kich thudc hat HORIBA LA-950, may HPLC Spectra System Thermo, may do the Zeta Phoremeter IV-CAD, RKIN ELME. Mdt sd thidt bj bao chd, kidm nghiem khae.
Phipccng phap nghien ciru
Che tao va danh gia mgt so dac tinh cda he nano piroxicam
Chd tao he nano piroxicam bdng phuang phdp nhu hda va bdc hai dung mdi sau dd ddnh gid hinh dang, kich thudc, c l u true tinh chat dien bd mat tidu phan nano, xdc djnh ham lugng dugc c h i t trong he nano'^'
Odng khd hdn djch nano vdi ede thdng sd:
ddng lanh - 70°C, s l y sa e l p d - 15°C, s l y thu e l p d 30°C.
Bao che hon djch nano piroxicam Hdn dieh nano duac bao chd b i n g phuang phap phdn tan. Khao sat anh hudng ciia ede thanh p h i n trong mdi trudng phan tan ddn dp dn dmh e l u true hda ly eiia hdn dieh dua vao tdc dd sa l i n g va hien tuang ket tu tidu phdn.
K § t q u a v a b a n l u a n Dong kho he nano hdn djch
Cac mau sau khi chd tao gdm cdc tieu phan hinh c l u ddu dan, bd mat n h i n vd da sd hat ed kich thudc nhd han 1000 nm, c l u true gdm hai p h i n : vd ngodi la polyme, nhan ben trong la duac c h i t (Hinh 1). San p h i m bde hai nudc d nhiet dp phdng ed the c h i t r i n c h i c , khd nghidn min, khd phan tdn trong nude, de sa l i n g va kdt
tu. Nhidu nghien ciru cho r i n g ddng khd la giai phdp tdi uu dd loai hdt dung mdi va tranh d u g c hien tugng kdt tu tidu phan, dn dinh c l u true hat '^ "' Vi vay, bien phap nay da d u g e dp dung de bde hai nude trong quy trinh chd tao he nano piroxicam. Sir dung cdc ta d u g c tao khung la glucose, sorbitol, manitol va PVA, san pham thu duge ed e l u true banh nguyen ven, the c h i t xdp, dp.xdp vd kieu xdp khac nhau. Nhu vay, cae ta duge tap khung ed anh hudng khac nhau ddn thd c h i t vd c l u true eiia san pham ddng khd, vd ehinh dieu nay han chd vide kdt tu edc tidu phan trong he.
. - . . . ^ • t Z ^ • • '
^' '-^f^'A \V-v.';:«'^
(a) (b) _
Hinh 1: Hinh dang, ciu triic cie tiiu phan trong he nano
(a) Anh chup tir kinh hien vi dien tir quet (b) Anh chup tir kinh hien vi dien tir truyin qua Hinh anh chup qua kinh hien vi dien tu' quet eho thiy, trong cae mau ddng khd, eac tieu phan duge chat dugc phdn tan ddu tren td duge tao khung, khdng kdt dinh nhau nhu trong cae mdu bdc hai nudc d nhiet dd phdng (ket qua nay the hien d hinh 2). Han nu'a, mdu sau khi ddng khd phan tan ngay trong nudc khi l i e nhe b i n g tay.
Didu dd eho t h i y r i n g qua trinh ddng khd giiip chd pham tai xdp han va tinh t h i m eiia cae tieu phan c h i t r i n tang len, didu nay cd y nghTa dac biet quan trpng trpng viec didu chd thudc dudi dang bdt khd dd pha hdn dich'^"'
1 ( a )
(d) tiim..iwiiii.nu,w
(b)
(e)
'^•m
1(0
5
(f) Hinh 2: Hinh anh cac tieu phan trong he nano sau khi ddng khd chup qua kinh hiin vi dien tw qudt (SEM)
(a): Px-Eudragit (PE) lam khd d nhiet do phdng; (b): PE ddng khd; (c):PE ddng khd vdi manitol;
(d): PE ddng kho vdi glucose; (e): PE ddng kho vdi sorbitol; (f): PE ddng khd vdi PVA
40 TAP CHl DUQC HQC - 7/2011 (SO 423 NAM 51)
Nghien CLFU - Ky thuat
Qua cac mau dd khao sdt, nhdn t h i y manitol va PVA the hien nhieu uu diem han ca ddi vdi he nano. Theo mdt sd nghidn ciru dd cdng bd, ede tdc gia cho r i n g PVA giiip dn dinh he nano trong qud trinh ddng khd '^''', vi vdy PVA la td duac tao khung dugc lua chpn cho nhu-ng qua trinh che tao tidp theo.
Nghien ciru anh hirdng cua moi trwdng phan tan den do on dinh cau true ly hoa cua hon dich
He nano sau khi chd tao duge kiem tra ham lugng duge c h i t b i n g phuang phdp s l e ky Idng hieu nang eao. Hdm lugng Px trong he la 7%, tuang duang vdi 75-80% luang duac c h i t thidt kd ban d i u . Cae mdu nay duac bao quan d nhiet dp phdng (25-35°C, dp I m 40-70%).
Sau 3 thang, san p h i m khdng cd s u thay ddi vd hinh dang, mdu s i c ciia banh ddng khd, ham luang dugc c h i t khdng thay ddi, dd phdn tan lai trong nudc vd soi dudi kinh hien vi khdng t h i y cd hien tuang ket tu tieu phan. He nay duac sir dung lam nguyen lieu bdo chd hdn dich.
Anh hwdng cua pH
He nano piroxicam duac phan tan vdi ty le 0,5% dugc c h i t trong mdi trudng nudc vdi cac gid tn pH khae nhau: 5,0; 6,0; 7,0; 8,0; 9,0 (dieu chfnh b i n g dung dieh NaOH 0,1 M vd HCI 0,1 M) Sau 1 t u l n bao quan d nhiet dp phdng, ket qua theo ddi cho t h i y pH cdng cao thi hdn dich cang kem ben, cac tieu phan dd ket tu tao ra eac chum tieu phan ldn, khd tach rdi, dac biet la vdi pH 8 va pH 9. Nguyen nhan Id do pH anh hudng true tidp tdi dien tich be mat ciia tieu phan keo. Do dd, nhO'ng khao sat tidp theo duac tien hanh trong mdi trudng trung tinh va acid nhe.
Anh hwdng ciia he dem
Phan tan duac c h i t vdi ty le 0,5 % vao cae cae he dem borat, eitrat, phosphat va acetat d cae gia trj pH 6,0; 6,5; 7,0; 7,5. De mdt t u l n d nhiet dp phdng, nhdn xet edc che p h i m b i n g cam quan. Kdt qua thu dugc nhu sau:
Vdi he dem phosphat va borat: hdn djch nhanh l i n g cdn. Ldp dich tren trong L i e manh, hdn dich khdng dat trang thdi nhu ban d i u . X u l t hien nhieu dam van ed the nhin t h i y b i n g m i t
thudng. Soi dudi kinh hien vi t h i y hien tugng tieu phdn ket tu thdnh mang
Vdi he dem eitrat va acetat, hon djch l i n g cham han, ldp djch tren trong md. Hdn djch trd lai trang thai ban d i u ngay sau khi l i e nhe Tuy nhien tai pH 7-7,5, khi l i e hdn djch, cd the nhin t h i y mdt vai dam tidu phan. Cd the ndi su tdc ddng eiia pH vd he dem den dp dn djnh eiia hdn djch la do he dem ehua c h i t dien ly, cac ion phdn ly trong dung djch tae ddng len Idp dien tieh tren bd mat cac tidu phan keo. Cae he dem chira cac ion vdi nguang keo tu khae nhau thi tdc dpng eua ehung len he nano piroxicam cung khac nhau. Oieu nay duac the hien mpt p h i n d thd zeta cua tieu phdn (ghi d bang 1)
Bang 1: Thi zeta cua tiiu phan nano piroxicam trong cac mdi trwdng
Mdi trw&ng Nudc tinh khi§t Dem phosphat pH 6 Dem phosphat pH 8 Dem eitrat pH 6 0 # m eitrat pH 8
The zeta (mV) -48,03
-8,01 -7,44 -12,42 - 10,14 Qua sd lieu d bang 1 ed the thay tac ddng ciia cac c h i t dien ly trong mdi trudng den tinh c h i t cua tieu phan nano r i t phirc tap. Trong dung djch dem phosphat, hien tuang ket tu tieu phan g i n lidn vdi giam the zeta cua tieu phan trong khi dd vdi dung dieh dem eitrat, mac du the zeta eiia tieu phdn r i t t h i p nhung hon dich lai dn dinh han. Didu nay cd the do cae ion trong dung dich cd nguang keo tu Idn hodc eac ion tao ldp do kep bao quanh tieu phdn vdi c l u true khdng gian edng kdnh nen han chd dugc su ket tu, de cd the kdt luan chinh xdc han vd vide nay c i n phai thuc hien them mpt sd thi nghiem phan tich khac vd theo ddi trong thdi gian ddi han.
Tuy nhien, vdi nhu'ng kdt qua budc d i u nhu tren, nhdm nghien cuu da lua chpn dung djch cd pH trong khoang 6-6,5 vdi he dem eitrat trong nhCrng thi nghiem tidp theo.
Anh hwdng cua chit bio quin
C h i t bao quan dugc khao sat gdm:
benzalkonium clorid (0,02%), thimerosal (0,02%) vd nipagin (0,05%). Quan sdt hdn dich
TAP C H i DUQC HQC - 7/2011 (SO 423 NAM 51) 41
Nghien CLFU - Ky thuat
trong 1 t u l n , nhan thay: hdn djch chira thimerosal vd nipagin sa l i n g nhanh han va cd hidn tugng kdt tu tieu phan. Oidu ndy the hien d hinh anh chup khi soi dudi kinh hien vi quang hpe (hinh 3) va ed the d u g e giai thich r i n g benzalkonium clorid la c h i t dien ly tra ddi vdi tidu phan nano piroxicam va cdn la c h i t didn hoat, lam tang tinh t h i m eiia eac tidu phdn nano trong nudc, tang dp bdn cua hdn dich.
Thimerosal Nipagin
Benzalkonium clorid
Hinh 3: Cac tiiu phan nano trong hdn djch chira cac chit bao quan khac nhau
Anh hwdng cua chit lam tang do nhdt o d lam giam tdc dp sa l i n g tidu phdn giup hdn dich dn dinh han, trong pham vi nghien ciru nay, chung tdi da sir dung hydroxypropyl methyl cellulose (HPMC)va PVA de lam tang dp nhdt, Ket qua khao sat chp thdy hai td duge nay ddu ed kha nang han chd hien tugng sa l i n g va kdt tu tieu phan trong hdn dieh.
Oe bao chd hdn dich nhd m i t , mdi trudng phan tan cdn d i n g truang. Can c u vdo dac tinh eiia tidu phan nano va tinh c h i t ciia mdt sd c h i t gay d i n g truang thudng dung, nhdm nghien eiru lua chpn c h i t khdng dien ly la manitol dd khdng lam anh hudng ddn dien tieh bd mat eiia tieu phan n h i m han che hien tugng kdt tu.
Ket luan
o d tai da nghien cuu bao chd hdn djch nho mat tu nguyen lieu nano piroxicam ddng khd vdi ta duac tao khung la PVA.
De tang dp dn djnh cua hdn djch, han chd dugc hien tugng kdt tu tieu phan, cac ta d u g c da d u g c khao sat va lua chpn n h u sau:
Nano piroxicam tuang u'ng vdi 0,5g piroxicam Acid citric monohydrat: 0,2 g
Natri hydroxyd: 0,1 g Benzalkonium clorid: 0,02 g Manitol: 4,00 g
Hydroxypropyl methyl cellulose: 0,1 g Nudc dd pha tidm vd: 100 ml
Summary
Nano suspension of piroxicam was prepared from lyophillzed nano particles (using PVA as matrix). In order to increase suspension stability and prevent the particles from flocculating, nano piroxicam suspension was formulated as follows:
Nano piroxicam (equivalent to 0.5g piroxicam);
Citric acid monohydrate: 0.20 g;
Sodium hydroxyde: 0.10 g;
Benzalkonium chloride: 0.02 g;
Mannitol: 4.00 g;
Hydroxypropyl methyl cellulose: 0.1 g;
Water for Injection q.s: 100 ml
Tai lieu tham khao
1. Nguyen Thi Mai Anh va cpng sy, Nghien ciru bao chg va danh gia mot so dac tinh cua he nano piroxicam.
Tap chi duoc hgc (2009), so 8/2009, trang 50-53.
2. Wassim Abdelwahed, Freeze-drying of nanoparticles: Formulation, process and storage considerations, Adv. Dmg Del. Rev. (2006), 58, p 1688-1713.
3. Khosro Adibkia et al,Piroxicam nanoparticles for ocular delivery: Physicochemical characterization and implementation in endotoxin-induced uveitis, J. Drug Target. (2007), 15, 6, p.407-416,
4. Min Kyung Lee, Cryoprotectants for freeze drying of drug nano-suspensions: Effect of freezing rate, J. Phanv. Sci, Inpress (2009), p.1-10.
5. Vikas Mittal, Advanced polymer nanoparticles (2011), CRC Press.
6. Ram N. Prajapati et al, Dendimer-mediated solubilization, formulation development and in vitro, in vivo assessment of piroxicam, Moi. Pharm. (2009), 6, 3, p. 940 - 950.
42 TAP CHi DUQC HQC - 7/2011 (SO 423 NAM 51)
