de xay dyng phuang trinh QSAR cd t h i irng dung de tinh toan va dy doan hoat tinh eiia cac d i n chit flavonol va flavanon tdng hgp khac.
K§t luan
Trong nghien ciru nay, 11 d i n c h i t flavonol va flavanon dugc tdng hgp va t i i n hanh thir nghiem doe tinh t i bao tren ddng t i bao ung thu vu MCF-7. Mdi quan he djnh lugng giO'a c i u triic hda hge va dgc tinh t i bao duge flin hanh nghien eiru. Sir dung phan tich binh phuang tdi thiiu tu'ng phin va phan tich danh gia cheo LOO tren 4 thdng sd md ta, phuang trinh QSAR dugc xay dyng vdi he sd tuang quan eao (r^ = 0,93 va (f (LOO) = 0,74). Phan tieh QSAR cung cho thiy thdng sd 'tuang quan dien tieh am tu'ng phin Q Q_PRC-' cua phan tir la y i u td quan trgng d i dy doan ddc tinh t i bao eua nhdm d i n c h i t Phan tir ed gia trj 'tuang quan dien tieh am tu'ng phin Q' cang nhd thi hoat tinh cang eao. Nghien eiru QSAR nay ed y nghTa trong viec thiit k i ra cac d i n chit eiia flavonol va flavanon vdi hoat tinh chdng ung thu eao han.
Summary
A total of 11 flavonol and flavanone derivatives was synthesized and tested for cytotoxicity activity on the mammary carcinoma MCF-7 cell line. A 2D quantitative structure-activity relationship (QSAR) model was generated to evaluate the effect of structural parameters on cytotoxicity. Partial Least- Squares (PLS) regression and cross-validation via
leave-one-out analyses on 4 molecular descriptors showed. the best result for antitumor activity. For the calculation of log(1/ICso), relative negative partial charge Q (Q_PRC-) showed to be the most predictive parameter The final equation was obtained with i^ = 0.93 and cf (LOO) = 0.74. This QSAR analysis provides a fast calculative, inexpensive, computational approach to predict cytotoxicity activity of new synthetic analogues.
Tai lieu tham khao
1. Li Y., Fang H., Xu W. Mini-Rev., Med. Chem., 2007, 7, 663.
2. Hoang Thj Kim Dung et al. Tap chi Dwac lieu, 2008, 13(4), 157.
3. Voigt W. Methods Mol. Med. 2005, 110, 39.
4. Molecular Operating Environment - MOE, Chemical Computing Group Inc., Montreal, H3A 2R7 Canada, http://www.chemcomp.com.
5. (a) Thai Khac Minh, Tran Thanh Dao. Tap chi Dwac hgc, 2007, 47(12). 24; (b) Thai Khic Minh, Huynh Thi Ngoc Phucng. Tap chi Dwac hgc, 2009, 49(2), 51.
6. Gasteiger J., Marsili M., Tetrahedron, 1980, 36, 3219.
7. ErtI P., Rohde B., Seizer P., J. Med. Chem.
2000, 43, 3714.
8. Murias M. et al., Bioorg, Med. Chem. 2004, 12, 5571.
9. Petitjean M, J. Chem. Inf Comput. Sci. 1992, 32,331.
10. Oprea T.I, J. Comp., Aided Mol. Des. 2000, 74.251.
Biro'c dau bao che sieu vi nang CO vo bao poly caprolacton
Dat vin 6k
Ngay nay, cdng nghe nano da dugc u'ng dung trong nhiiu nganh cdng nghiep trong dd ed cdng nghiep duge p h i m . Cdng nghe nano da duge bude d i u irng dung trong cdng nghiep duge d i bao e h i eae sieu vi nang (nanoeapsules) cd chira hoat chit, tao thanh
Dang Thj Tuyet Nhung, Pham Ngoc Bung, Vo Quoc Anh, Trjnh Thj Tuyet Truang dgi hoc Duac Ha Noi cac he van chuyen thude cd hieu qua eao han va cd tinh hudng ddi tugng han. Zile va cdng sy '^' da bao c h i thanh cdng sieu vi nang chu'a griseofulvin, lam tang kha nang hda tan cung nhu sinh kha dung eua hoat c h i t nay. Fonseea va cdng sy '^' cung ghi nhan kha nang bao e h i sieu vi nang chira natri diclofenac giai phdng
TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 33
eham. Ngoai ra, sieu vi nang da duge quan tam nghien ciru tai nhiiu nai tren t h i gidi vl kha nang cai thien do dn djnh cua e h i phim va cd t h i dugc bao e h i d i dang tren quy md edng nghiep. Mdt vai thir nghiem dung sieu vi nang lam he d i n tnjyin eho cac chit cd hoat tinh sinh hge nhu phytosterol, eae acid beo khdng no da chire hay mgt vai vitamin ua d i u da cho kit qua kha quan'^l
Carotenoids la eae s i c td cd nhiiu trong rau, hoa qua. Cac earotenoid nhu beta earoten va lyeopen ed hoat tinh chdng oxi hda cao nen cd t h i giiip phdng chdng cac benh nguy h i i m nhu ung thu. Tai Viet Nam ed nhiiu loai rau qua cd chira cac earotenoid quy gia nay trong dd dang chii y la gic. D i u g i c dugc ep tir mang hat g i c cung da b i t d i u dugc sir dung nhu mgt ngudn earotenoid tren quy md edng nghiep. Cae nghien eiru sa bd eho t h i y d i u g i c cd ham lugng earotenoid r i t eao trong dd bao gdm ea eae chit chdng oxi hda manh nhu lyeopen va beta earoten. Tuy nhien, cac earotenoid nay r i t nhay cam vdi eae y i u td mdi trudng nhu anh sang, nhiet do va oxi. Vi vay r i t e i n cd cac phuang phap bao e h i san p h i m ed kha nang bao quan dn dinh eae c h i t de phan huy nhu lyeopen and beta earoten d i ed t h i tan dung dugc tdi da ngudn nguyen lieu quy nay.
Muc dich cua nghien eu'U nay la bao c h i eae sieu vi nang ed chira d i u g i c d i cai thien do dn dinh cua eae hoat c h i t ed trong d i u g i c . Cae y i u td anh hudng d i n qua trinh bao c h i sieu vi nang va hieu qua dn djnh hoat c h i t cua sieu vi nang cung se duge nghien eiru va ban luan.
Nguyen lieu va phu'ang phap
Nguyin lieu
D i u g i c mdi ep dugc cdng ty Duge Hai Duang (Viet Nam) cung c i p . Poly caprolacton (PCL) va poly vinyl alcohol (PVA) mua cua hang Aldrich Sigma (My). Delios S va V duge hang Cognis (Nhat Ban) eung c i p . Chuin lyeopen va beta earoten mua eua hang Wako (Nhat Ban).
Cae dung mdi sir dung dat tieu chuin phan tich.
Phu'ang phap khuich tan - nhu tu'O'ng (Emulsion - Diffusion IVIethod EDM)
Phuang phap khuich tan - nhu tuang sir dung pha nude va pha dung mdi. Pha nude la nude bao hda ethyl acetat, pha dung mdi la ethyl acetat bao hda nude. PVA duge hda tan trong pha nude, cac thanh phin edn lai gdm PCL, Delios, d i u g i c dugc hda tan trong pha dung mdi. Sau dd pha nude va pha dung mdi
6irac phdi hgp vdi nhau d i tao nhu tugng.
Bude khuich tan dugc thye hien b i n g each bd sung nude c i t vao nhu tuang d i tao thanh hdn djeh loang ehira sieu vi nang mdi duge tao thanh. C i t quay hdn djch thu duge d ap suit giam thu duge hdn djeh dac chira sieu vi nang.
Trong trudng hgp sii' dung cae c h i t nhu hda thi Tween duge bd sung vao pha nude edn Span duge hda tan trong pha dung mdi.
Phu'O'ng phap ling dong polymer tren b§
mat khi dung moi djch chuyin (interfaclal polymer deposition following solvent displacement SDM) goi t i t la phu'ang phap djch chuyin dung mol
Phuang phap nay cung sir dung hai pha ban d i u la pha nude va pha dung mdi. Pha nude la nude c i t hda tan PVA va Tween. Pha dung moi gdm PCL, Delios, d i u g i c va Span duge hoa tan trong aceton. T i i p dd pha dung mdi dugc phdi hgp vdi pha nude d nhiet do phdng thu duge hdn djch loang ehira sieu vi nang mdi dugc tao thanh. Lge va c i t quay hdn dich thu duge dudi ap s u i t giam thu duge hdn djch dac chu'a sieu vi nang.
Danh gia ty le hoat chit trong hdn djch sau qua trinh bao nang (goi t i t la hieu suit bao nang)
Tdng ham lugng lyeopen va beta earoten trong hdn dich ehira sieu vi nang Suae xae djnh sau khi giai phdng lyeopen va beta earoten ra khdi sieu vi nang. Mang bao ngoai eua sieu vi nang duge pha hiiy b i n g tetrahydrofuran. Djch chiit tetrahydrofuran thu dugc dem l i c vdi dung djeh NaCI bao hda. Dung mdi dem c i t dudi ap s u i t giam thu dugc c i n khd. Hda tan c i n trong hdn hgp dung mdi methanol : DCM (6:4) co chua BHT rdi mang di djnh lugng lyeopen va beta earoten. Cae c h i t nay dugc dinh lugng bing s i c ky Idng hieu nang cao (HPLC) tren may Finnigan Spectra (Thermo Finnigan, San Jose, California, My) vdi detector mang diet quang. Qua trinh phan tach dugc thye hien tren cot Inertsil ODS-3 (250 x 4,6 mm ID, 5 um) (GL Sciences, Tokyo, Nhat Ban). He dung mdi gdm dichloromethan va acetonltril (6:4) (dung mdi A) va methanol (dung mdi B). Dung mdi A co 0,05% BHT la c h i t chdng oxy hda. Chuang trinh chay s i c ky duge thye hien nhu sau: d i u tien la he gdm 70% dung mdi A, 30% dung mdi B trong vdng 5 phiit, sau dd la 80% dung mdi A, 20% dung mdi B trong vdng 5 phut. Cot dugc
34 TAP CHI DirOC HOC - 12/2010 (SO 416 NAM 50)
trd v i trang thai ban d i u va dugc can b i n g trong vdng 5 phut nu'a. Tde do ddng la 1,5 ml/phut T h i tich tiem m i u 20 [i\. Dinh lugng lyeopen va beta earoten d bude sdng 472 nm.
Xae djnh eae earotenoid trong m i u duge t i i n hanh bing each so sanh thdi gian luu cua peak tren s i c ki dd va so sanh phd h i p thu phan tir trong pham vi 300 - 600 nm eua eae peak e i n xae djnh vdi s i c ky eua c h i t chuin.
Hieu suit bao nang (%) duge tinh theo edng thire:
H(%) = m*100/M
Vdi m la tdng lugng lyeopen va beta earoten cd trong hdn dich ehua sieu vi nang
M la tdng lugng lyeopen va beta earoten ed trong d i u ban d i u dem di bao e h i .
Cac hdn dich dac chu'a sieu vi nang sau khi bao e h i duge bao quan trong Ig nut kin va d i d diiu kien thudng (nhiet do phdng va cd anh sang chiiu). Sau 2 t u i n bao quan ham lugng earotenoid trong hdn djch duge djnh lugng lai va so sanh vdi ham lugng ban d i u de xae djnh do dn djnh cua cac earotenoid trong d i u g i c .
Ty le cae thanh phin trong edng thu'C gdm ty le PCL, ty le PVA, ban c h i t d i u Delios (V hay S) va ty le chit nhu hda dugc thay ddi d i khao sat anh hudng cua cac thanh phin nay d i n hieu suit bao nang va do dn dinh cua hoat c h i t trong sieu vi nang. Cdng thu'C trung tam va ty le thay ddi cae thanh phin eiia 2 phuang phap duge tdm t i t trong bang 1.
Bang 1: Cdng thirc trung tam va cac thanh phin thay ddi trong 2 phwang phap bao chi sieu vi nang
EDM SDM
Cong thirc chinh
Thay doi
Cong thu'C chinh
Thay doi
Pha nuac
Nude 40ml PVA, 2,5% 2 va 3%
50 ml
1% 0,5 va 1,5%
Pha dung moi Dung moi
PCL Delios Dau gac
10ml 2% . 5%
1%
1 va 3%
25 ml 1%
5%
1%
0,5 va 1,5%
Tyle Tween -
Span
0 1:1; 1:2
va2:1 1:1 1:2 va 2:1 Hinh anh eiia sieu vi nang dugc chup bang kinh hiin vi dien tir quet (SEM) tren may TAP CHi DirOC HOC - 12/2010 (SO 416 NAM 50)
FESEM Hitachi S-4800. Phan bd kich thude fleu phan dugc xac djnh bang ky thuat tan xa laser tren may Horiba LA 950. T h i zeta cua sieu vi nang dugc do b i n g phuang phap dien di.
K i t qua va ban luan
Scy bo thip kha nang bao ve hoat c h i t cua mang PCL
Lyeopen va beta earoten la nhO'ng hgp c h i t cd mau dd tao nen mau dd eua d i u g i c . Khi bj oxi hda cae hgp c h i t nay chuyen thanh cae dang chit khae khdng mau vl vay d i u g i e eung bj m i t mau d i n trong qua trinh bao quan. Dae biet d ndng do t h i p va ed mat eua eae c h i t khae thi d i u g i e cang nhanh bj m i t mau do qua trinh oxi hda lyeopen va beta earoten xay ra d i dang. Trudc khi t i i n hanh khao sat anh hudng cua cae thanh p h i n trong edng thu'C bao c h i d i n hieu s u i t bao nang ehung tdi da thii' kha nang bao ve hoat c h i t cua mSng PCL nhu sau:
tiin hanh bao e h i 2 m i u ed edng thu'C gidng nhau nhung 1 m i u ed mang bao PCL edn 1 m i u khdng ed. Sau khi bao e h i 2 m i u nay d i u dugc bao quan d nhiet do phdng ed anh sang trong 2 t u i n . K i t qua eho t h i y m i u ed mang bao v i n r i t b i n mau sau thdi gian bao quan edn m i u khdng cd mang bao- m i t mau hoan toan thanh hdn djch due nhu su'a. Nhu vay ed the sa bg t h i y ring sieu vi nang tao thanh cd kha nang bao ve hoat c h i t nhd mang bao PCL.
Dac tinh vat ly cua sieu vl nang
Hinh anh chup tren kinh hiin vi dien tu' quet (hinh 1) eho t h i y cae sieu vi nang duge tao thanh ed hinh c i u kich thude khoang tu' 300nm d i n 600 nm. Khi xae djnh phan bd kich thude tieu phan k i t qua eho t h i y dudng kinh trung binh eiia sieu vi nang la 413,19 nm khi sir dung EDM va 411,64 nm khi sir dung SDM. T h i zeta ciia cua sieu vi nang tao thanh bdi 2 phuang phap la tuang duang nhau va d i u tuang ddi cao (-63 mV vdi EDM va -60 mV vdi SDM).
.sg^g
IMS l<20.0kSE(M) 5/12C009
Hinh 1: Hinh anh sieu vi nang chup tren Minh hiin vi dien tw quet
35
Phuo'ng phap nhu tu^yng - khuich tan (EDM) K i t qua nghien eu'U anh hudng eua cac Anh hwcrng cua cac thanh phan trong thanh phin trong cdng thirc d i n hieu s u i t bao cdng thirc den hieu suit bao nang nang bing EDM dugc trinh bay trong bang 2.
Bang 2: Anh hwang cua thanh phin trong cdng thirc din hieu suit bao nang diiu chi bing EDM
Cong thwc EDMO EDM1 EDM2 EDM3 EDM4 EDM5 EDM6 EDM7
Thanh phan
PCL 2%, PVA 2,5%, khong dien hoat PCL
(PVA 2,5%, khong dien hoat) PVA
(PCL 2%, khong dien hoat)
Tween.Span r p r i 9% PVA ? <!%
1 % 3%
2%
3%
1:1 2:1 1:2
Hieu suit bao nang (%) Delios V
66,52 74,89 58,49 69,92 39,85 58,65 72,45 82,94
Delios S 65,28 69,77 77,4 62,89 57,14 59,42 41,73 66,23 Delios S va V la cac hdn hgp triglyceride cd
ty le eae acid beo khae nhau. K i t qua cho t h i y khdng ed sy khae nhau ed y nghTa thdng ke (f- test, P>0.05) v i hieu s u i t bao nang khi sir dung Delios S hay V. Nhu vay ty le acid beo khac nhau giO'a Delios S va V khdng anh hudng d i n hieu suit bao nang khi bao e h i sieu vi nang bing phuang phap EDM.
Trong khoang ty le chit tao mang bao (PCL va PVA) khao sat (tu' 1 % d i n 3%) hieu suit bao nang tuang ddi dn djnh (khoang 60-75%) va ed xu hudng tang khi ty le mang bao giam. Vdi PVA, khi tang ty le eua chit nay thi eung lam giam hieu suit bao nang trong ca 2 trudng hgp dung Delios V va S. Khi cd mat chit dien hoat hieu suit bao nang it thay ddi so vdi edng thire trung tam va khdng cd xu hudng tang hay giam rd ret.
Dp on djnh cua hoat chat trong sieu vi nang diiu chi bing EDM qua thai gian bao quan
K i t qua dugc trinh bay trong bang 3. Nhin ehung vdi cac edng thirc bao c h i sii' dung Delios V mire do giam ty le hoat c h i t trong sieu vi nang it han so vdi eae edng thu'C bao ehi sii' dung Delios S. Dang chu y la khi ed mat cac c h i t dien hoat, cac m i u bao e h i d i u bj phan Idp va m i t mau sau 2 t u i n bao quan chirng to sieu vi nang khdng dugc tao thanh d cac mau nay. Cdng thu'C trung tam cd do dn djnh tuang ddi tdt (ty le giam ham lugng hoat c h i t la 5%
vdi Delios V va 10% vdi Delios S). Tuy nhien edng thu'C vdi ty le c h i t tao mang bao t h i p (1%) eung cd hieu s u i t bao nang cao va do dn djnh khdng khac so vdi edng thu'C trung tam nen co the chgn ty le nay de bao c h i sieu vi nang.
Bang 3: Do dn dinh cua sieu vi nang diiu chi bing EDM sau 2 tuin bao quan
Cong thirc
EDMO EDM1 EDM2 EDM3 EDM4 EDM5 EDM6 EDM7
H sau bao che (%)
66,52 74,89 58,49 69,92 39,85 58,65 72,45 82,94
Delios V H sau bao quan (%)
61,32 69,52 58,19 37,01 37,92
- - -
Mu'C do giam
5,2 5,37
0,3 32,91
1,93
- - -
H sau bao che (%)
65,28 69,77 77,4 62,89 57,14 59,42 41,73 66,23
Delios S H sau bao quan (%)
54,28 53,9 43,06 42,88 36,97
- - -
Mirc do giam 11,00 15,87 34,34 20,01 20,17
- - -
Ghi chu: -: khong xac dinh do mau bi mat mau; H sau bao che: ty le ham Iwang earotenoid co trong sieu vi nang so vai ban dSu ngay sau khi bao chi; H sau bao quan: ty le ham Iwgng earotenoid con lai trong sieu vi nang so vai ban diu sau khi bao quan.
Phu'O'ng phap djch chuyin dung mol (SDM) K i t qua dugc trinh bay trong bang 4. Kit Anh huKrng cua cac thanh phan trong qua thdng ke cho t h i y hieu s u i t bao nang bing cong thCrc den hieu suat bao nang SDM t h i p hgn hieu s u i t bao nang b i n g EDM
36 TAP CHI DlTOC HOC - 12/2010 (SO 416 NAM 50)
vdi ca 2 loai Delios V va S (P <0,01). Tuy nhien, ed t h i nhan thiy trong SDM ty le c h i t tao mang bao duge sir dung t h i p han nhiiu l i n so vdi EDM. Khi ty le c h i t tao mang bao dugc tang len tu' 0,25% d i n 0,5% va len d i n 0,75% thi hieu suit bao nang eao nhit d mu'C 0,5%. Nhu vay ty le chit tao mang bao khdng ty le thuan vdi hieu suit bao nang va edng thu'C cd ty le 0,5%
PCL eho hieu suit bao nang cao n h i t
Tuang ty nhu k i t qua ddi vdi EDM, cac edng thire bao c h i vdi Delios V va S bing SDM eho hieu s u i t bao nang sai khae nhau khdng ed y nghTa thdng ke (f-test, p>0,05). Ty le PVA cua cdng thu'C trung tam eung cho hieu s u i t bao nang eao nhit nghTa la khi tang hay giam ty le nay d i u khdng cai thien duac hieu s u i t bao nang. Trong khi dd ty le c h i t nhu hda khdng ed anh hudng rd ret d i n hieu s u i t bao nang.
B a n g 4 : Cong thirc
SDMO SDM1 SDM2 SDM3 SDM4 SDM5 SDM6
Anh hwang cua thanh phan trong cdng thwc den hieu suat bao nang dieu che bang SDM Thanh phan
PCL 0,5%, PVA 1 % , Tw/een:Span 1:1 PCL
(PVA1%,Tween:Span 1:1) PVA
(PCL 0,5%, Tween:Span 1:1) Twppn'^nfln r P n n <!% PVA 1%1
0,25%
0,75%
0,5%
1,5%
2:1 1:2
Hieu suat bao Delios V
49,43 23,10 21,02 21,83 28,34 31,87 43,32
nang (%) Delios S
37,88 22,93 30,62 53,71 23,10 27,88 27,99 D8 dn djnh cua hoat chat trong sieu vi nang
dllu chi bing SDM qua thd'i gian bao quan Kit qua duge trinh bay trong bang 5. Cae cdng thire bao e h i vdi Delios V va S ed mirc do giam ham lugng hoat c h i t tuang ddi gidng nhau. Tuy nhien, khi thay ddi ty le c h i t dien hoat cac m i u d i u bj m i t mau sau thdi gian bao quan
chirng td sieu vi nang khdng tao thanh d cae m i u nay. Cd t h i t h i y r i n g c h i t dien hoat ed anh hudng r i t quan trgng d i n kha nang tao thanh sieu vi nang d ea 2 phuang phap bao ehi. Khi xet anh hudng eua PVA eho t h i y ty le PVA len d i n 1,5% thi m i u khdng tao dugc sieu vi nang.
B a n g 5:
Cong thwc
SDMO SDMI SDM2 SDM3 SDM4 SDM5 SDM6
D p dn djnh cua sieu vi nang diiu chi bing SDM sau 2 tuin bao quan
H sau bao che (%)
49,43 23,10 21,02 21,83 28,34 31,87 43,32
Delios V H sau bao quan (%)
34,98 14,45 15,87 16,43
- - -
Mirc do giam 14,45
8,65 5,15 5,4
- - -
H sau bao che (%)
37,88 22,93 30,62 53,71 23,10 27,88 27,99
Delios S H sau bao quan (%)
28,25 12,13 18,74 41,76
- - -
Mirc do giam
9,63 10,8 11,88 11,95
- - -
Ghi chu: -: khong xac dinh do mau bi mat mau; H sau bao chi: ty le ham Iwgng earotenoid co trong sieu vi nang so vai ban dau ngay sau khi bao chi; H sau bao quan: ty le ham Iwgng earotenoid con lai trong sieu vi nang so vai ban dau sau khi bao quan.
Ket luan
Hal phuang phap bao c h i sieu vi nang thir nghiem d i u ed t h i tao thanh dugc sieu vi nang ehira d i u gie. Cac thanh phin trong edng thu'C bao c h i ed anh hudng vdi cae mu'C do khae nhau d i n hieu suit tao sieu vi nang eung nhu do on djnh eua sieu vi nang sau thdi gian bao quan.
Summary
Two methods for formulating nanoeapsules were applied to produce Gic oil-loaded nanoeapsules with the purpose of Improving the stability of lycopene and beta carotene contained in Gic oil. The encapsulation efficiency as well as the influencing factors was also investigated. In
TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 37
general, nanoeapsules improved the stability of carotenoids In Gic oil but exclpients in formulations affected both encapsulation efficiency and stability of carotenoids in nanoeapsules.
T a i lieu t h a m k h a o
1. Zili, Z, Star S., and Fessi H., Preparation and characterization of poly-e-caprolactone nanoparticles containing griseofulvin. International Journal of Pharmaceutics, (2005), 294(1-2), 261-267.
2. Fonseea, L. S. d.; Silveira, R. P.; Deboni, A. M.;
Benvenutti, E. V.; Costa, T. M. H.; Guterres, S. S.;
Pohlmann, A. R., Nanocapsule@xerog8l microparticles containing sodium diclofenac: A new strategy to control the release of drugs, Intemational Journal of Phamiaceutics, (2008), 358, 292-295.
3. Ribeiro, H. S.; Chu, B.-S.; Ichikavifa, S.;
Nakajima, M., Preparation of nanodispersions containing p-carotene by solvent displacement method. Food Hydrocolloids, (2008), 22, 12-17.
A r
Nghien ciru dieu che allantoin
Truffng Phu'O'ng, Le Thj Ngoc Trang, Dang Thj Kieu Nga Truang dgi hoc Y Duac TP. HCM
Dat van de
Allantoin la hoat c h i t ed trong nhiiu cay ed nhu Comfrey (Symphytum officinale L) Dioscorea Rhizoma va nhiiu cay khac, hien duge SU' dung phd biin trong cae c h i p h i m thude va my p h i m dung eho da...'^"^'. Allantoin cd tae dung lam liin seo, md v i t tham, ngu'a mun, da s i n . Ngoai ra edn duge chT djnh trong viem da do tiip xue, cdn trung e i n , viem da dj U'ng, m i day, ndi ban, sung t i y , mam do...Allantoin edn dung trong eae thude v i m i t nhu mdi mit, xung huyit k i t mac, cam giac m i t khd ehiu sau khi bai hay do bui ''*'^''
Allantoin duge dua vao duge dien mdt sd nude nhu BP 2009, USP30'^'^'. Mdt sd xi nghiep dugc d Viet Nam ed k i hoaeh san x u i t eae c h i p h i m chira allantoin nhung nguyen lieu hien tai hoan toan nhap ngoai, viec chiit x u i t allatoin tu' Id hgi khdng hieu qua, kem kha thi. Qua tim hiiu ehung tdi thiy ed the tdng hgp allantoin tir nhCrng nguyen lieu re t i i n d i k i i m nhu ure, glyoxal, hydrogen peroxyd'^'^'. Trong bai nay ehung tdi thdng bao k i t qua nghien ciru tdng
hgp allantoin vdi hy vgng tao them ngudn nguyen lieu eho edng nghiep Dugc Viet Nam.
Ddi tu'O'ng va phu'O'ng phap nghien
CLPU
D 6 I tu'O'ng
N H , P . t l : 158,1 H H
C4H6N4O3 o K , l N ^ o H ^
Ten khoa hge: 2,5-dioxoimidazolidin-4-yl ure.
Nguyen lieu
Cae nguyen lieu trong qua trinh tdng hgp allantoin nhu ure, glyoxal 30%, hydro peroxid 30%,... tinh khiit hda hge ed ngudn gdc Trung Qudc.
Phu'O'ng phap nghien ciPU Tong ho'p allantoin
Qua trinh tdng hgp allantoin gdm 2 giai doan:
- D i i u e h i glyeouril tu' glyoxal va ure
Glyoxal dugc hd biin thanh bis-gemdiol, trong mdi trudng acid phan irng loai nude tao vdng. Tuy thugc vao ty le mol giO'a ure va glyoxal ma phan U'ng tao ra monouril hay glyeouril.
H ,0
I
H O
2H2O HO, ,0H CH C'H
Hd bH
H + CH - ^
= ^ C ' H
HsO^'vO^OHj H2N + 2 ; ; ^ o
H2N
-4H20 H H
H H
:c=o
OH -NH -NH OH
38 TAP CHi DU'O'C HOC - 12/2010 (SO 416 NAM 50)
