Y Hpc TP. Hb Chi Minh * Tap 20 * Sb 6 * 2016 Nghien cuu Y hpc
TC/ONG TAC THU6C G I C A BAI THUOC THAN THONG TRUC U" THANG VA MELOXICAM TREN MO HINH T H U C NGHIEM DANH GIA
TAC DUNG KHANG VIEM - GIAM DAU
Huynh Thanh Nhdn*, Nguyen PhuongDung**
TOMTAT
Tinh hinh vd m^c dich nghien cuiu: Tucmg tdc thud'c - thdo dugc Id mdt van di quan trgng Hen thuc hdnh lam sdng. Cho deh nay, tdi lieu nghien clhi ve tuang tdc thudc ~ thdo dugc con rai hqn che; tan su^ tucmg tdc thuc su giiea thud'c vd thdo dugc rc&ddng ke nhung v&n chua cd nghiin cie ndo cho biii dugc con so chinh xdc.
Mdt Hong nhimg binh ly phd'biai ihu&ng dugc dOu tri phoi hgp giiea thud'c T&n dugc vd Ddng dugc la benh ly ca xuang khap nham muc Heu khdng viim - gidm dau. Nghien ciiru ndy diegc tiin hdnh nham ddnh gid tucmg tdc thud'c Idii ph&i hgp bdi thud'c Thdn thdng true ie thang (TTTUT) vd meloxicam trin thuc nghiim, gdp phan ddnh gid hieu qua vd su an todn ciia phdi hgp 2 loqi thu6'c ndy trong dieu tri.
Thiei ke nghien cdu: Nghiin cieu thuc nghiim.
Doi tuong vd phuang phdp nghien cieu: Cao dqc Than th&hg true ie thang dugc bdo che tai Phong thi nghiem Y hgc co truyen, die phdm meloxicam do Cdng ty TNHH LD Stada Viet Nam sdn xudi. Chudt nhat Hang chiing Swiss albino, Hgng lugng 18 - 22g mua tqi Viin Pasteur TP. Ho Chi Minh. Sie dung md hinh gdy viim thuc nghiem bdng carrageenin, do thetich chdn chugt trudc vd sau khi udng thud'c 1 gi&, 3 gia, 5 gi& vd 24 gio deddnh gid tdc dung khdng viim cap cita thud'c nghiin cuu. Sie dung md hinh g&y u hat bang vien bdng cotton, can trgng lugng u hat sSy khd sau khi umg thuoc 7 ngdy, tdc dung khdng viim mqn ciia thud'c nghien cum dugc ddnh gid bang ty li phdn trdm uc chi'Hgng lugng u hat. Sie dung md hinh gay dau quan bang cdch Him axit oxeHc vdo Idioang mdng bung chudt sau khi cho chudt udng thud'c 1 gi&, dan sd'can dau quan mdi 5 phiit Hong vdng 30 phiit deddnh gidc tdc dung gidm dau ciia thud'c nghiin cieu.
Ket qud chinh: Cdc Id dmi tri meloxicam 8 mg/kg, TTTUT 14,44 g/kg vd 2 16 diiu tri phoi hgp deu thehien hiiu qud gidm do phu chdn chudt tqi cdc thai diem 1 gid, 3 gi&, 5 gio vd 24 gia sau khi uohg thud'c, khde biet co y nghia thdng ki so vdi Id chieng dm (p < 0,05). Hiiu qud gidm phii giiia 16 ph6i hgp meloxicam 8 mg/kg vd TTTUT 14,44 g/kg so vdi Id phdi hgp meloxicam 4 mg/kg vd TTTUT 7,22 g/kg tuang duong nhau tqi t^ cd th&i dian nghien dm(p> 0,05). Tai cd cdc Id diiu tri, ngoqi trie 16 meloxicam 4 mg/kg deu cd tdc dung iic che'sie phdt Hiin u hqi so v&i Id doi chimg vai su khde biit co y nghia thdng ke (p < 0,01). Tdi ca cdc 16 diiu Hi deu ldm gidm sd'can dau quan co y nghia thd'ng ki so vdi Id chieng dm. Hiiu qud gidm dau cita 2 16 phdi hgp tuang duang v&i Id meloxicam 8 mg/kg
Ket ludn: Cao dqc Thdn thdng Hue u thang an todn fD™ = 72,2g/kg), cd tdc dung Ididng viim, gidm dau Hin chuot nhdt Tdc dung khdng viem - gidm dau khi phdi hgp meloxicam vd TTTUT a cd 2 lOu diu tucmg ducmg nhau vd bdng vdi tdc dung cim meloxicam 8 mg/kg.
Titkhoa: Th&n thd'ng true ie thang, meloxicam, khdng viim, gidm dau, carrageenin, u hat, axit axetic.
' Tmng tim Y te huy?n Lao An - Binh Dinh ** Khoa Y hpc co truyen - DH Y Dirge TP. HCM Tdcgid lien lac: BS. Huynh Tiianli Nhan DT: 0903765586 Email: khongbiet26(^yahoo.com
215
N g h i e n cuu Y hpc Y Hpc TP. Hb Chi Minh * Tap 20 * Sb 6 * 2016
ABSTRACT
STUDIES ON INTERACTIONS BETWEEN SHENTONG ZHUYU DECOCTION AND MELOXICJ^M ON EXPERIMENTAL ANTI-INFLAMMATORY& ANALGESIC MODELS
Huynh Thanh Nhan, Nguyen Phuong Dung * Y Hoc TP. Ho (Zhi Minh * Vol. 20 - No 6 - 2016:215 - 221 Background and aims. Hab - drug intaadions is a key issue in dinical pracHce. So frr, the study data of herb - drug interactions are very limited and the true prevalence of hab - drug intaactions is substantial but unknown'^'. One common condition, which is usually concomitant Heated zoith Haditional medidne and western medidne for anti - inlammatory and analgesic effects, is musculoskeletal disease. This study was conducted to evaluate drug intaactions when combination of Shentong Zhuyu tang (STZYT) and meloxicam in mice, contributed to the assessment of the effecHveness and safety of concomitant Heatment
Study design and Setting: An experimental study.
Materials and methods: Shentong Thuyu decoction wae prepared in pilot, meloxicxim produced by Ltd Stada Vietnam. Swiss albino mice wdght 18 - 22g, from Pasteur InsHtute in HCMC were injected carrageenine to cause hind paw oedema. The acute anti-inftammatory effect was evaluated by comparing the hind paw volume before and after 1-hour, 3-hour, 5-hour and 24rhouroral adminisHaHon of drugs. Using the model (^granuloma formation frllowing implantation cotton pellets in mice, weighing dried granuloma after 7-day taking drugs, the chronic anti-inflamatory activity of drugs wae measured bythe percentage of granuloma inhibition. Using the writhing test with a chemical irritant (acetic acid) injeded into the peritoneal cavity of mice after taking drugsl hour, counting the numba of writhes every 5 minutes during 30 minutes after injection to evaluate the analgesic
Results. The study groups including m.eloxicam 8 mg/kg, STZYT 14.44 g/kg and the two groups of combination show the inhibition effed of the mouse paw oedema more statistically significantly effective than conHol group at all the study periods (after 1 hour, 3 hours, 5 hours and 24 hours). The oedema inhibiHon effed tif the group meloxicam 8 mg/kg plus STZYT 14.44 g/kg and the group of meloxicam 4 mg/kg plus STZYT 7.22 g/kg are equivalent at all the study periods. All of the study groups excluding the group cf meloxicam 4 mg/kg have the granuloma inhibiHon effect statistically different compared with ihe conHol group. All the study groups reduce the numba of writhes staHsHcaly significantly compared with the control group. The analgesic effed cfthe two combination groups is equivalent to the study group of meloxicam 8 mg/kg
Conclusions: Shentong Zhuyu decoction is safr (Dnm = 72.2 g/kg), has anti-inflammatory arui analgesic effect in mice. The anH-inflammatory and armlgesic effet of the combinaHon betiveen meloxicam and STZYT at both doses are equivalent to the group of meloxicam 8 mg/kg.
Key words: Shentong Zhuyu decoction, meloxicam, anti-inflammatory, analgesic, carrageenine, acetic add, granuloma.
DAT VAN DE ^ ^ t teong nhung yeu to anh huong den chat luong dieu tri phoi hgp do la su tuong tac giiJa Hien my, xu huong dieu tri ket hop giua Y ^^g^ ^, ^.^ jf,j„ j „ „ , Du Ueu hien co ve tuong hoc hien dai va Y hoc co tmyen ngay cang tro y^^^~._^^^ j „ „ ^ ^ ^ j , ^ ^~ , ^ ^ j , nen pho bien trong thuc hanh lam sang. Trong ^^^^ ,4^ f^^^ s„ ^^^ j ^ ^ nghien oiu nao do, viec s i dung Tan duoc phoi hc?p Dong duoc ^^^ ^^ ^^^^^ ^^^ ^ u n g chSc cMn con nWeu hon da tro thanh van de can duoc xem xet can than j ^ ^ ^ g ^^ f^^^g^ _ OaiSc, vi moi loai thao duoc dua tren co so bang chiing khoa hoc de dat duoc ^ - ^ ^ ^ ^ hoat chat co tac dung duoc ly, trong hieu qua dieu tri tcfi uu va han che tac dung phu. y ^ j,„g(, flmong cW co 1 hoat chat chinh.
216
Y Hgc TP. Hb Chi Minh * Tap 20 * So 6 * 2016 Nghien cuu Y hpc
Benh ly co xuortg khop (CXK) la nhom benh xay ra kha pho bien trong cong dong, anh huong nhieu deh chat luong siic khoe va chat lugng cuoc song ciia benh nhan. l a n suat m§c benh CXK 6 nuoc ta len tdi 47,6% so nguoi tren 60 tuoi'^'. Mgt nghien cuu danh gia Ihuc trang dimg thuoc Y hoc co truyen tai cac tinh phia Bac da cho thay nhom benh CXK la nhom benh den kham chiia benh bang thuoc va cac phuong phap khdng dimg thuoc YHCT nhieu nhat {Pham Huu Khanh, Nghiem H u u Thanh - 2003). Nhieu tuong tac thuoc giiia D6ng dugc - Tan dugc da dugc ghi nhan 6 benh nhan co xuong khop, dang nhac d&i la nhom khang viem khong steroid'^'. Trong dieu tri benh ly co xuong khop, bai thuoc Than thong true li thang, xuat xii tir sach Y lam cai thac ciia tac gia Vuong Thanh Nham, da dugc chiing minh hieu qua khang viem, giam dau tren thuc nghiem va lam sang'^^'*-*'. Chua co nghien ctiu nao danh gia hieu qua khi ph6i hgp meloxicam va TTTUT, do do chiing toi tieh hanh nghien ctiu nay nham danh gia tuong tac tren tac dyng khang viem - giam dau khi phbi hgp meloxicam va TTTUT tren chupt nhat.
D6llUqNG-mUtlNGPHAPNGHIENCUtJ Dbi hipng nghien cuu
Cao dac Than Ihong true li thang (ilTUT) dugc bao che tir bai tiiuoc cb phuong gom 12 dugc Ueu (EXrong quy 9g, Hong hoa 9g, Dao nhan 9g, Nguu tat 9g, Xuyen khung 6g, Mgt dugc 6g, Ngu linh chi 6g, Dia long 6g, Chich cam tiiao 6g, Tan giao 3g, Khuong hoat 3g, Huong phu che 3g). Bao che va luu mau t^ii Phong thi nghiem Y dugc cb truyen, Dai hgc Y dugc TPHCM. Khi diing, lay cao dac khoi lugng thich hgp pha trong nuoc cat the iich thich hgp theo lieu dimg de cho chugt uong.
Meloxicam 7,5mg, do Cong ty Stada Viet Nam san xuat, khi sir dung, lay vien nen tan bgt min pha voi nuoc cat the tich thich hgp theo lieu dimg de cho chuot uong.
Dpng vat thu nghiem
Chugt nhat trang due, chiing Sunss albino mua 6 Vien Pasteur TP Ho Chi Minh, 6 - 8 tuan tubi, trgng lugng 18 - 22 g, dimg de nghien ciiu dgc tmh cap, khang viem cap va giam dau quan do axit axetic va chugt 6 - 8 tuan tuoi, trgng lugng 24 - 26 g dimg d&' nghien a i u tac dung khang viem man (mo hinh gay u hat). Trong suot qua trinh thii nghiem, chugt dugc nuoi trong dieu kien on dinh ve dinh duong (thuc phaim cam vien, nuoc tiJ do) va che do dueu sang thich hgp.
Phucmg tien
Carragenan y (Sigma Aldrich - My), axit axetic, nuoc muoi sinh ly 9%o, bong, ethanol.
Can say am MettlerToledo, model HB43 - Halogen (Thyy S), may do the tich phii Plethysmometer 7140 (Ugo Basile - Y).
Fhuong phap nghien curu Phuong phdp bdo che cao dac TTTUT
Can cac dugc lieu voi khoi lugng thich hgp tuong ling 20 thang thuoc (1500g) sac vdi nuoc 2 lan, gop chung cac dich chiet co each thuy d&i khi duge cao dac dat do am < 20%.
Phuongphdp thvc nghiem dgc titih cap Lieu lam chet 50% thii vat thii nghiem (LDso) dugc tmh theo cong thiic Karber - Behren ho^c lieu tbi da khong co thii vat nao chet (Dmax).
Tren ca sd xac dinh lieu LDsoho^c Dntc^ta xac djnh lieu co tac dung dugc ly khoang 1/5 - 1/10 lieu LDahoac Dmax dS thu tac dung khang viem giam dau.
Chugt dugc tien hanh phan 16 nhu sau:
Lo 1 (16 chung am): Ubng nude c§ft 0,lml/10g.
Lo 2 (DTI): Uong meloxicam Ueu 8 mg/kg/ngay.
L6 3 (DT2): Uong meloxicam lieu i mg/kg/ngay.
Lo 4 (DT3): Uong cao long TTTUT heu 1/5 LDso h o a c Dmax.
N g h i e n ciiu Y hgc Y Hgc TP. Hb Chi Minh * T?p 20 * Sb 6 * 2
L6 5 (DT 4): Ubng cao long TTTUT Keu 1/10 LDso h o a c Dmax.
Lo 6 (PH 1): Ubng cao long TTTUT Meu 1/5 LDso hoac Dmnx va meloxicam lieu 8mg/kg/ngay.
Lo 7 (PH 2): Ubng cao long T n U T 1/10 LDso hole Dmax va meloxicam lieu 4mg/kg/ngay.
Phuong phdp ddnh gid tdc dung khdng viem cap thuc nghiem (Winter-1962)<^
Do the tieh ban chan phai sau aia chupt nhat trudc thi nghiem. Tiem dung djch carrageenin 1% (0,05mL) vao phan gan ban chan phai. Do the tich ban chan phai sau ciia chugt sau khi tiem carrageenin 3 gio, chon cac chugt co do phu chan chuot dat tren 50% dua vao tiiii nghiem va phan 16. Cho chugt uong thuoc the tich 0,lmL/10 g theo 7 nhom (n = 8) nhu tren.
Tac dung khang viem dugc bieii dien bang
% miic do giam sung phii ehan chugt trong 16 thir nghiem so vdi 16 chiing uong nuoc cat va nhom doi chiing uong meloxicam 8mg/kg.
Phucmg phdp ddnh gid tdc dung khdng viem man thuc nghiem'^
CM sgi cotton tiianh timg doan n g ^ trgng lugng 10 ± 1 mg, ve tron, say kho. Cao sach 16ng vimg lung chugt, dimg t^u keo bam 116 nho de tach da lung ra kh6i ldp co, cay b6ng cotton.
Khau bang chi de noi lien vet mo. Chia ngau nhien chugt thanh 716 nhu tren, m6i 16 8 chugt, cho chuot ubng thuoc 0,lmL/10g trong vong 7 ngay:
Doi ngay thii 8, mo boc tach u hgt dem di say kho d 60°C den khbi lugng kli6ng doi. Tac dung lie che u hat dugc bieu thi bang ti le giam trgng lugng trung binh aia u hat d 16 dimg thubc so vdi 16 chiing uong nude cat va nhom dbi chiing ubng meloxicam 8mg/kg.
Phuong phap danh gja tac dung giam dau (Koster-1959)P>
Tac dung giam dau cua cac thubc dugc Hen hanh tren mo hinh gay dau quan bang axit axetic.
Chia ngau nhien chugt thanh 7 16 nhu tren, moi 16 8 chugt:
Cho chugt ubng thubc, sau 1 gid, tiem axit axetic vao khoang mang bung chugt. Dem sb con dau quan moi 5 phiit trong vong 30 phiit.
Phuong phap x^ ly sb lieu thbng ke Ket qua dugc tiinh bay d dang: X + SE Cac sb Heu tiiu thap duge xti ly bang phuong phap thbng ke y sinh bang phan mem SPSS 16,0.
So sanh tri so giiia cac 16 dieu tii dugc thuc hien bang thu^t toan thbng ke One way ANOVA, T - test Student Su khac biet giiia cac 16 duoc coi la CO y nghia khi p< 0,05 va quy udc:
(o): p >0,05; *: p < 0,05; **: p < 0,01; ***: p
<0,001 i d T Q U A Dgc tinh cap
Khong tim dugc LDso. Xac djnh dugc Dmax = 72,2 g dugc heu kho/kg.
Nhu vay, U^u dugc hgn de thii nghiem tac dung dugc ly la: 1/5 Dmax = 14,44 g dugc l i ^ kh6/kg tuong duong vdi 1 thang thubc
Va 1/10 Dmax= 7,22 g dugc lieu kh6/kg tuong duong vdi 1/2 thang thubc.
Tuong tae giiia bai thuoc Than tiiong tn^c li thang va meloxicam tren tac dung khang viem cap.
Bdng 1. KB. qud dd phii chan chugt cita cdc 16 tqi cdc th&i diem NC Lo ttiLF nghiem
LSI: Chiing am L62:
Meloxicam 8 mg/kg
% giam phu so 16 chiing
Qq phii {%) sau 1 gid' (V1) 52,95 ±13,13 30,25 ±14,69"
42,88%
Do phu (%) sau 3 gio- (V3) 44,16 ±14,91 20.79 ±12,26"
52,95%
Dp phu (%) sau 5 gicr (V5) 36,68 ±14,91 12,92 ±12,01"
64,78%
DQ phii (%) sau 24 giv (24) 35,33 ± 9,37 10,74±15,42"
69,61%
Y Hpc TP. Hb Chi Minh * Tap 20 * Sb 6 * 2016 Nghien ciru Y hgc
Ld thCp nghiem L Q 3 Meloxicam 4 m/kg
% giam phu so 16 ctil>ng L5 4 TTTUT 14,44 g*g
% giam phii so 16 chijng L6 5 TTTUT 7.22 gftg
% giam phii so 16 chu^g L6 6 lyle! 8 mg/l<g + TT 14,44 g/tcg
% giam phii so 16 chiing L6 7 lylel 4 mg/kg+TT 7,22 g/kg
% giam phii so i6 chi>ng
Dp phii {%) sau 1 gio- (VI) 41,85110,62'°'
20,98%
35,97 ± 16,83*
32,07%
40,50 ±13,65'°' 23,52%
22,23 ± 9 , 6 9 "
58.02%
35,55 ±15.97*
32,87%
DQ phii (%) sau 3 gio- (V3) 38,61 ± 16,30'°'
12,56%
22,03 ±19,37*
50,12%
34,93 ±15,81'°' 20,91%
19,63 ±8,28**
55,54%
19,67±10,81- 55,46%
Dp phO (%) sau 5 gio"
(V5) 23,88 ± 13,62'°'
34,89%
15,40±15,30*
68,00%
25,11 ±11,5/°' 31,54%
11,35 ±9,44**
69,05%
17,91 ±16,87*
55,17%
DQ 'phii (%) sau 24 gi6'(24) 31,04 ±13,69'°'
12,13%
20,04 ± 12,95- 43,28%
31,50*12,68'°' 10,83%
9,29 ±14,90"
73,71%
16,19±16,96*
54,17%
Nhan xet: Cac 16 dieu tri meloxicam 8 mg/kg, r m i T 14,44 g/kg va 2 16 dieu tri phbi hgp deu tiie hien hieu qua giam do phii chan chugt tai cac thai diem 1 gid, 3 gid, 5 gid va 24 gid sau khi uong thuoc khac biet c6 y nghia thong ke so vdi 16 chiing am (p < 0,05).
L 6 dieu tri meloxicam 4 mg/kg va 16 TTTUT 7,22 g/kg khong co tac dung khang viem cap d mgi thdi diem so vdi 16 chiing am (p > 0,05).
Tai tat ea cac thdi diem sau khi uong thuoc, 16 dieu tri TTTUT 14,44g/kg va 216 dieu tri phoi hgp deu the hien hieu qua giam phii tuong duong vdi 16 dieu tri meloxicam 8mg/kg. (p >
0,05).
Tai thdi diein 1 gid sau ubng thubc, hieu qua khang viem cap aia 16 dieu tri phoi hgp lieu cao meloxicam 8 mg/kg va TTTUT 14,44 g/kg so vdi 16 chiing bieu thi xu hudng tot hon khoang 35%
so vdi 16 dieu tri meloxicam 8mg/kg, tuy nhien Bdng2. Tdc dung ciia thud'c dieu tri len trgng lugng u h
su khac biet khong co y nghia thbng ke (p > 0,05).
Xu hudng nay tai thdi diem 3 gio, 5 gid va 24 gid chi dao dgng tCr 4,89 6,59% so vdi 16 Mmloxicam 8 mg/kg va kh6ng co y nghia thbng ke (p > 0,05).
Hieu qua giam phu giiia 16 phoi hgp meloxicam 8 mg/kg va TTTUT 14,44 g/kg so vdi 16 phbi hgp meloxicam 4 mg/kg va TTTUT 7,22 g/kg tuong duong nhau tai tat ca thdi diem nghien ciiu (p > 0,05).
Nhu vay, phbi hgp lieu thap meloxicam va TTTUT giiip mang lai tac dung hiep dong tren tac dung khang viem cap tren mo hinh gay phii chan chugt bang carrageenin.
Tuong tae giiia bai thubc Than thong true li thang va meloxicam tren tae dung khang viem man
1-6 L6 1 • Chii'ng am L6 2. Meloxicam 8 mg/kg L6 3: Meloxicam 4 mg/kg Lo 4: TTTUT 14,44 g*g L6 5: TTTUT 7,22 g/kg L6 6. Mel 8 mg/kg + TT 14,44 g/kg
L6 7: Mel 4 mg*g + TT 7,22 g*g Tnpng luvng
u h^t (mg) 8,98 ±1,27 6,41 ±0,43 7.38 ±2.09 5.68 ±0.54 7.20 ±0.79 6.44 ±1,50 6,78 ±0,99
Ti 1^ % giam trpng luvng u hat so voi Id Chiang
28,62%
17,82%
37.86%
19,82%
28,29%
24,50%
p so voi 161
"
(0)
"
"
"
p so voi 16 2
(0)
"
(0)
*
(0) p so voi
164 (0)
*
"
(0)
**
p s o v o i 166
(0) (0) (0) (0) (0)
p so voi 16 7
(0) (0) (0) (0) (0)
219
Nghien cuu Y hpc Y Hpc TP. Hb Chi Minh * Tap 20 * So 6 •2016
Nhan xet: Tat ca cac 16 dieu tri, ngoai trir 16 meloxicam 4 mg/kg deu eo tac dung lic che su phat trien u hat so vdi 16 dbi chiing vdi su khac biet CO y nghia thbng ke (p < 0,01).
Tac dung khang viem man ciia 16 pho'i hgp meloxicam 8 mg/kg va TTTUT 14,44 g ^ g tuong duong vdi 16 Meloxicam 8 mg/kg, 16 TTTUT 14,44 g/kg va 16 phoi hgp meloxicam 4 mg/kg va TTTUT 7,22 g/kg (p > 0,05).
Tac dung khang viem man ciia 216 phbi hcfp meloxicam 8 mg/kg va TETUT 14,44 g/kg va 16 phbi hgp meloxicam 4 mg/kg va TTTUT 7,22 Bdng 3. Tdc dung gidm so'can dau quan cim cdc 16 tqi cdc
g/kg kh6ng khac biet co y nghia thbng ke va tuong duong vdi tac diing ciia 16 meloxicam 8 mg/kg vdi ti le lie che trgng lugng u hat Ian lugt la 28,29%, 24,50% va 28,62% (p > 0,05).
Nhu v?y, phbi hgp Heu thap meloxicam va TTTUT giiip mang lai tac dung hiep dong cho hieu qua khang viem man tren mo lunh u hat b3ng vien cotton.
Tuong tac giiia bai thubc Than thong true li thang va meloxicam tren tac dung giam dau
th&i diim NC
1
L6 161 Chu'ng am
L62 Meloxicam 8 mg/kg
% giam so vol 16 chutig am L63 Meloxicam 4 mg/kg
% giam so v6l 16 chimg Sm L64 TTTUT 14.44 g/kg
% giam so voi 16 chiing am 1 L6 5 1 TTTUT 7.22 g/kg
"'/a giam SO voi 16 chirng am L66 Mel 8 mg/kg + TT 14,44 g/kg
% giam so v^i Id ch^ng 3m L6 7 Mel 4 mg/kg + TT 7,22 g/kg
% giam so voi Id chiing 3m
S6 con qu|n dau (s6 ccn/S phut) 0 - 5 phut
5,62 ±1,51 2,25±2,19"
59,96%
3,12±1,46"
44,48%
4,75 ±2,18'°' 15,48%
6,00 ±2,98'°' -6,76%
3,38 ±2,33*
39,86%
4,12±1,96'°' 26,69%
5 - 1 0 phiit 13,88±1,73 7,12±1,46"
48,70%
11,76±
3,24*
15,35%
3,60 ±2,00**
38,76%
10,75 ± 4,23'°' 22,55%
3,75 ±3,28"
29,76%
9,25 ±1,04"
33,36%
10-15 phut 12.38 ±
1,51 7,88 ± 0,84"
36,35%
10,12 ± 2,42*
18.26%
6.62 ± 2.26**
54.60%
8,62 ± 2,88"
30,37%
6,75 ± 1,83"
45,48%
7,75 ± 2.32"
37.40%
l S - 2 0 phiit 10,75±2.25 3.50 ±0.93"
39.53%
8.00 ±1.20- 25.586 4.62 ±1,19"
57,02%
3,00 ±2,27"
44,19%
5,26 + 2,38"
51,16%
5,62 ±1,30"
47,72%
2 0 - 2 5 phot 9,75 ±1,83 4,62 ±1,06"
52,62%
7,38 + 1,51*
24,31%
3,12±1,00"
68.00%
6.25 ±2.12"
35.90%
4.12±1.96"
67,74%
4,76 ±1,75"
61,28%
25-30 phot 7.62±1.19 3.88 ±1.13"
49,085 5,62 ±1,92*
26,26%
2,75 ±1,04"
63,91%
4,88 ±1,46"
35,96%
3,00 ±0,93"
60,63%
4,25 ±2,05"
44,23%
30 phiit 60,00 ±5,16 32,25 ±3,62"
46,25%
46,00 ±6.00"
23.33%
29.3814.72**
51,03%
42,5 ±7,29"
29,17%
32,25 ±3,06- 46,25%
35,75 ±5,65"
40,42%
Nhan xet: Tat ca cac 16 dieu tri deu the hien tac dung giam sb Ian dau quan so vdi 16 chiing ubng nude cat trong thdi gian 30 phiit sau khi tiem axit axetic.
Tac dung giam sb con dau quan d 16 dieu tri TTTUT 14,44 g/kg va 216 phbi hgp tuong duong vdi 16 meloxicam 8 mg/kg (p > 0,05) va tot hon 16 meloxicam 4 mg/kg (p < 0,01) trong qua trinh quan sat 30 phiit sau khi gay dau quan bang axit axetic.
L6 TTIUT 7,22 g/kg chi tiie hien tac dung giam dau tii thdi diern 10 - 15 phiit dSi het 30 phiit (p < 0,01), tac dung giam dau quan trong suot 30 phiit kem hon 16 meloxicam 8 mg/kg co y nghia thbng ke (p < 0,01)
Quan sat trong 30 phiit, 16 TTTUT 14,44 g/kg CO hieu qua giam tong sb Ian dau quan tot hem 16 TTTUT 7,22 g/kg (pM< 0,01). L6 phbi hgp TnXJT 14,44 g/kg vdi meloxicam 8 mg/kg co tac dung giam dau quan trong 30 phiit tuong duong vdi
220
Y H g c TP. H b Chi M i n h * T?p 20 * S b 6 * 2016 Nghien ci3eu Y hgc
16 phbi hgp TTTUT 7,22 g/kg vdi meloxicam 4 mg/kg (p7-s> 0,05).
Ngugc Igii, 16 phdi hgp TTTUT 7,22 g/kg vdi meloxicam 4 m g ^ g the hien tac dung giam so con dau q u ^ tbt hon 16 don trj meloxicam 4 mg/kg tai thdi diem 15 - 20 phiit va 20 - 25 phiit, khac biet co y nghia tiiong ke (p < 0,01). Tong sb con dau quan quan sat tiong 30 phiit ciia 16 giam toi 40,42%, khac biet co y nghia so vdi 23.33% d 16 meloxicam 4 mg/kg (p < 0,01).
Nhu vay, khi phoi hgp 2 Keu thap da mang l?i tac dung hiep dong giiip lam tang phat huy tae dung cua meloxicam 4 mg/kg va TTTUT 7,22 g/kg tren mo hinh dau quan do add acetic d chugt nhat trang.
KETLUAN
Xac dinh dugc Dmax ciia cao TTTUT d chugt nhat tiang la 72,2 g dugc Ueu/kg, tuong duong voi 5 Ian lieu dimg tien lam sang, chiing to cao TTTUt CO do an toan cao.Cao TTTUT tiie hien tac dung khang viem, giam dau tien cac m6 hinh gay phii chan chugt bang carrageenin, mo hinh gay u hat bang vien cotton va m6 hinh gay dau qu|ffi bang axit axetic. Tac dung khang viem - giam dau khi phdi hgp meloxicam va TTTUT d ca 2 lieu deu tuong duong vdi hieu qua ciia meloxicam 8 mg/kg. Tren mo hinh khang viem cap, phdi hgp meloxicam 4 mg/kg vdi TTTUT 7,22 g/kg da the hien tac dung hiep dong khi lam
giam do phu chan chugt tot hon co y nghia thdng ke so vdi 16 meloxicam 4 mg/kg va 16 TTIUT 7,22 g/kg. Tren m6 hinh u hat va m6 hinh gay dau quan, phbi hgp meloxicam va TTTUT heu thap ciing tiie hien tac dung hiep dong tbt hon 16 meloxicam 4 mg/kg.
TAI U E U THAM KHAO
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2 Nguyen Thi Nggc Lan (2013) Benh hgc co xucmg khap ml khoa, Tai ban Bn thir ba. Nha xuat ban Giao due Viet Nam, tr 346 - 354.
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Nha xuat ban lao dong. trl37 -138.
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6 Tran Thai Ha, Nguyen Trgng Thong. Nguyen Nhuoc Kim, Ph^mThi Van Anh (2011). Tac dung giam dau va chong viem man tuih ciia Cao long Than thcnig tryc ir tren thuc nghiem.
Top dli n ^ i m ciiw 1/hoc, tgp 72, so 1, tr. 87 - 93 7 Vien ducrc l i ^ (2006). Phuimg phdp n^ien ciru tac dung duac iy
cua thuoc tie duuc thdo, Nha xuat ban khoa hpc va ky thugt, tr.
58-53,140-149
8 W. Holden, J. Joseph va L Williamson (2005). Use of heriwJ remedies and potential d m g interactions in iheiunalology outpatients. Ann Rheum Dis. 64(5), p. 790
hlgdy nhan bai hao- Ngdy phdn bien nhan xet bdi bdo:
Ngdy bdi bdo duoc dang:
30/07/2016 3J/08/2016 25/11/2016
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