Tieu ban: Cdc chdt co hoat tinh sinh Iwc ISBN: 978-604-913-012-0
NGHIEN c t r u PHAT TRIEN VA HOAN THIEN BAI THUOC HEANTOS HO TRO GIAI D Q C MA TUY
Tran Van Sung Vien Hda hgc
18 - Hoang Qudc Viet. Cau Giay. Ha Ndi Email: tranvansungvhh@gmai 1 .com
Tom tat:
Heantos la mdt bdi thudc ngudn gdc thdo dugcciia^Viit Nam di hd trg dieu tip cai nghien ma tiiy. Ndm 1989 Heantos Id bdi thudc hd trg dieu tij cai nghien ddu tien dugc Bd Y ti thdm dinh. Tu ndm 1995 Vien Hda hgc thudc Vifn Khoa hgc vd Cdng nghe Viet Nam dd tiin hdnh cdc nghien ciru khoa hgc de phdt triin bdi thudc theo hir&ng ndng cao tinh an todn vd hieu qua cimg nhir^ tieu chudn hda cdc dugc lieu vd quy trinh san xudt cita thudc. Din nay bdi thudc Heantos dd hodn thdnh thu nghiem ldm sdng giai dogn 111 theo chi dgo cua Bd Y ti (>380 benh nhdn dnh nguyen) vd chd cdp phep san xudt. hru hdnh. Hiin nay tru&ng dgi hgc Essen (CHLB Dire) vd tru&ng dgi hgc Columbia Anh (UBC, Canada) dang nghien ciru ldm sdng vd nghien ciru ca che tdc dung cua Heantos.
Abstract:
Heantos is a Vietnamese herbal medicament for treatment of drug addiction. In 1989 Heantos was the first anlidrugmedication, scientifically evaluated by the
Vietnamese Ministry of Health (MOH). In 1995 the Institute of Chemistry, VAST has carried out the investigation for further development of Heantos. Lots have done until now for improuvment of efficacy and safety of Heantos including the study for its standardisation. Heantos has passed phase 111 of clinical study guided by the MOH (>380 patients) and waits now for the authorisation. The University of Essen (Germany) and the University British Columbia (Canada) are carrying out now clinical study and study on the mechanism of action of Heantos.
I. Dat van de
Te nan nghien hut, tiem chich ma tiiy da va dang la van de ldn ddi vdi toan cau ciing nhu ddi vdi mdi qudc gia, trong dd cd Viet Nam. O Viet Nam theo thdng ke chua day dii thi cd khoang hon 300.000 ngudi nghien ma tiiy. Ma tuy ciing la mdt trong nhirng nguyen nhan chinh dan den cac can benh hiem ngheo lay truyen qua dudng tiem chich nhu HIV/ AIDS, viem gan sieu vi triing .... Ddng thdi nghien ma tiiy ciing la nguyen nhan ciia tdi pham cudp giat, giet ngudi, dem lai nhieu ndi dau cho gia dinh va xa hdi. Mdt dieu dang phai quan tam niia la te nan ma tiiy cd the lam anh budng den sir phat trien ciia gidng ndi, dan tdc.
Mdt trong nhirng nhiem vu quan trgng ciia cdng tac phdng chdng ma tiiy la cai nghien cho ngudi nghien, dua bg trd lai tai hda nhap cdng ddng. Day la van de rat phiic tap, ddi hdi nd lire ciia toan xa hdi, ciia ca be thdng chinh trj. De giai quyet van de nay thi khau dau tien la phai dieu trj cat con cho benh nhan, giai phdng hg khdi sir le thudc vao ma tuy.
0 cac nude phuong tay ngudi ta diing mdt vai loai thudc tdng hgp nhu methadone, buprenorphine, naloxone de cai nghien ma tuy ...Tuy nhien, cac thudc dd ciing cd tinh gay nghien nhung nhe hon heroin. Ngudi ta ggi dd la Lieu phdp thay thi"' (substitution therapy), tiic la ldy loai ma tiiy nhe hon thay thi cho ma tuy nang, giam dan lieu cho den khi ngudi
Hoi nghi Khoa hoc ky niem 35 ndm Vien Khoa hoc vd Cong nghe Viet Nam - Hd Noi 10'2010
benh het them nhd ma tiiy. "Lieuphdp thay thi'' nay it dan den thanh cdng, nhieu trudng hgp benh nhan lai mac nghien chinh loai thudc dieu trj. O mdt sd nude phuong ddng, trong dd cd Viet Nam, ngudi ta cd sir dung mdt sd bai thudc dan tdc tren co sd thuc vat va ddng vat de cai nghien ma tuy. Theo triet ly y bgc phuong ddng thi nguyen nhan ciia nghien ma tiiy la do mdt can bang "Am" I "Dirong". Mudn chira khdi benh thi phai thilt lap lai can bdng "AnC I
""Duong". Thudc dan tdc giiip lam viec nay. Can luu y la cac thudc dan tdc vl nguyen tdc la khdng gay nghien. Vi vay, sir dung thudc dan tdc de cai nghien ma tiiy khdng phai la mdt lieu phap th^ay the va cd uu diem hon cac thudc tdng hgp. Vdi un dilm nay nen cac bai thudc thao dugc hd trg cai nghien ma tuy rat dugc cac nha khoa hgc trong nude va quoc tl quan tam
II. Mot so chat gay nghien chii yeu dang duoc su dung
- Morphin. Nha hda hgc Diic Sertuerner da tach dugc morphin tir thudc phien ldn ddu tien vao nam 1806. Phai mat 120 nam sau thi Robinson va Schoef mdi xac djnh dugc cdu triic hda hgc ciia morphin. Morphin la hgp chdt quan trgng nhdt trong nhua ciia qua cay thudc phien (Papaver somniferum) thudc hg thudc phien (Papaveraceae). Cay thudc phien cdn cd ten la phii dung, anh tir tiic, a phien, tiic xac, anh tiic xac, cii tuc xac [1].
Morphin la mdt ancaloid khung morphinan, it tan trong nude sdi hoae chloroform, tan trong cdn, ac^eton, etyl acetat. Morphin dugc sir dung lam thudc giam dau cho nhung benh nhan phai phdu thuat n|ng, ung thu giai doan cudi .... Lilu cd tac dung giam dau d ngudi ldn la 10 mg [2]. Nhugc diem ciia morphin la gay bung phdn manh d trung uong thdn kinh va din tdi lam dung chat nay. d lieu cao hon morphin se dan din trang thai tuong tu nhu me.
Morphin cd tac dung ire che co quan hd hdp, d lilu > 50 mg morphin cd tbi gay ra hien tugng ngirng hd hap. Ddng vat gam nham it nhay cam hon vdi morphin. Vi du: LD50 ciia chugt nhdt bdng dudng uong la 524 mg/kg tbi trgng, bdng dudng tiem la 140 mg/kg thi trgng. Morphin khdng dugc sir dung lam thudc giam dau trong san khoa. Trong trudng hgp bj ngd ddc morphin dan tdi ngirng thd ngudi ta cd the sir dung chdt cd tac dung ddi khang vdi morphin, vi du nhu naloxon (nhdm methyl d nguyen tir nito cua morphin dugc thay bdng gdc allyl) dl dieu trj.
- Heroin, la san pham ban tdng hgp tir morphin. 6 heroin hai nhdm hydroxyl ciia morphin da bj axetyl boa tao thanh ddn xudt diaxetat. Heroin la mdt chdt ma tuy manh, trong CO the no se dugc chuyen hda thanh morphin. Heroin tac ddng len be thdn kinh trung uong va phong be trang thai sg bai va dau ddn ciia con ngudi, lam mdt kha nang nhan bilt ciia cac co quan thu cam. Mdt dieu rat ly thii la: kha nang phat sinh sinh hgc ciia morphin khdng chi gidi ban trong cac loai thudc hg thudc phien (Papaveraceae). Ngudi ta da phat bien thdy lugng vlt cua morphin (1-10 pg/g) trong cd va rau xa lach [3,4]. Ngoai ra, morphin dugc tim thdy trong CO the ddng vat cd vii, ke ca con ngudi [5,6]. Ngudi ta da phan lap dugc morphin va cac dan xuat nhu morphin -3-0- sunphat, morphin -6-0- acetat morphin, -6- glucuronid trong tiiy sdng va trong vd tuyen thugng than ciia chugt cong. Tac dung giam dau ciia morphin -6- glucuronid manh hon ciia morphin tdi 120 ldn [7,8]. Ben canh morphin, trong co thi ddng vat cd vii va con ngudi cdn cd mdt ldp chdt ggi la ""morphin ndi sinh"'' endogenous morphine).
""Morphin ndi sinh""\\ du nhu endorphin, entepbalin va dynorphin la cac peptid cd tac dung giam dau va ciing tac dung tren ciing mdt thu thi d nao bd nhu morphin (vi du |a-receptor).
Song, morphin ben hon ve hda hgc va cd tinh chgn Igc ban nhilu d ii-receptor so vdi endorphin.
- Cdn sa. Cay can sa cdn ggi la cay gai ddu, gai meo cd ten khoa hoc la Canabis saliva L. thudc hg gai meo (Cannabinaceae). Ddu tien ngudi ta trdng cay nay dk ldy soi det vai va lay dau. Khai niem cannabinoid dk chi cac boat chdt ciia cay cdn sa cung nhu cac din
Tieu ban: Cdc chdl co hogt tinh sinh hoc ISBN: 978-604-913-012-0
xudt ban tdng hgp cua chimg. Cac hgp chat nay ngoai tac dung len be than kinh nhu mgt loai ma tiiy cdn cd nhilu hoat tinh dugc ly khae nira. Vi du: cannabinoid lam giam them nhof cocain, mdt chdt ma tuy phd biin cd ngudn gdc tir chau My [9], lam tang tri nhd [10.11]- chiia benh glocom mdt (tang nhan ap) [12]. Hang Hda dugc Bayer cua CHLB Dire mdi dua ra thi trudng mdt dugc phdm tren co sd cac hoat chat ciia can sa cd ten la Sativex dimg de chtra benh khdp va dau thdn kinh, ung thu... [ 13].
Cac san phdm tir cay can sa nhu mariuana (nggn hoa ciia cay cai) hoae nhua (hashish) da dugc sir dung tir ngan ddi nay. Hoat chdt chinh cua can sa la A'' tetrahydrocannabinol (THC). Chdt nay tac ddng len tl bao thdn kinh trong nao thdng qua viec gan ket vdi thu the CBl {CBl receptor), mdt protein tren bl mat cua no ron thdn kinh. Thu the CBl nay ciing cd vai trd tuong tac vdi cac ""cannabinoid ndi sinh"" do co the tu tdng hgp [14].
A'* - THC cdn cd ten la nabilon (dang racemat) hoae dronabinol dugc sir diing lam thudc chdng ndn d My vdi ten thuang mai la Marinol®- A'^-THC nlu sir diing d lieu thap se cd cam giac sang khoai, de chju, cdn dugc dimg dk chira benh hen, benh mat (tang nhan ap). 0 lilu rdt cao nd gay ra cam giac sg hai, hoang tudng. Nam 2007 E.B. Russo da cd mdt bai tdng quan kha ddy du vl Cdn sa [15]. Ljch sir phat triln va sir dung Cdn sa cung dugc tdng quan trong cdng trinh ciia R. Mechoulam[21].
- Cocain. Ia mdt alcaloid cd khung tropan. Ten khoa hgc ciia cocain la (IR)-3exo- benzoyIoxy-2-exo-tropancarboxylic axit methyl ester, cdng thirc phan tir la C17H21NO4, dnc 98°C, [a]D = -30 (CH3OH). Cocain cd vj ddng, tan tdt trong dung mdi hiru co, tan vira phai trong nude, dung djch cd tinh hoi kiem.
Cocain la thanh phdn chinh ciia cay cdca {Erythroxylum coca) thudc hg edea (Erythroxylaceae). Cocain cd ddc tinh , LD50 =17,5 mg/kg the trgng doi vdi chugt cdng theo dudng tiem. Cocain cd tac dung gay te tai cho va ldn ddu tien dugc sir dung de gay te trong phlu thuat la vao nam 1884. Do tinh chdt de phan buy va gay nghien nen ngay nay cocain khdng dugc dimg trong y tl niia. Ngudi dan viing Anden d Nam My ngay nay vin cdn cd thdi quen nhai la coca trdn vdi vdi. Do vdi cd tinh kiem nen khi nhai cocain se bj thiiy phan thanh ecgonin, chdt ecgonin khdng gay nghien. Dien hinh ve boat tinh ciia cocain la lam tang kha nang lam viec va lam irc che sir ngon mieng. Ngudi nghien cocain cd the dimg dudng tiem chich, hut, hit. Sir dung thudng xuyen cocain se dan den le thudc ve tam than nhung khdng le thudc ve the chat. Sau khi ngimg sir dung cocain thi khdng cd hdi chimg cai xuat hien.
Ci My cocain hydrochlorid (ten bi mat la koks tuyet) va cocain dang tu do (ten bi mat la crack) la ma tuy dugc sir dung thudng xuyen nhat. Ngudi ta da tim ra chat 4-iodococain la mdt chat ddi khang vdi cocain manh nhat, cd the dimg de dieu trj nghien cocain. Nghien cacain dac biet khd dieu trj, nghien cocain de lai di chiing ve tam than nang. Cac nghien cim da chi ra rang su dung cocain lau dai cd the dan den cac trieu chimg nhu benh Parkinson. Bdi vay ngudi ta ciing sir dung boat chat bromocriptin (Parlodel) de kiem soat hdi chimg nghien cocain.
Mdt sd chat gay nghien cd ngudn gdc tdng hgp hay dugc diing tren thj trudng hien nay bao gdm amphetamin, methamphetamin va 3,4- methamphetamin (MDMA), cd ten la ecstasy.
- Methamphetamin. la loai ma tiiy tdng hgp dugc sir dung rdng rai nhat tren thi gidi dac biet la d BSc My va vimg vien ddng, trong khi amphetamin va cac chat nhdm ecstasy (MDMA, MDA, MDEA) dugc sir dung da sd d chau Au. 6 cac nude thudc khdi Thjnh vugng chung thi methamphetamin va methcathinon (ephedron) la ma tuy tdng hgp chinh.
Hoi nghi Khoa hoc ky' niem 35 ndm Vien Khoa hoc vd Cong nghe Viet Nam - Hd Noi 10 2010
R = H: Morphin
R = Ac: Heroin Delta-9-tetrahydro canabinol (A-9-THC)
NH,
Amphetamine
R, = H; RJ = COOCH3; (-) - Cocain Ri = COOCH3; R2 = H : (+) - Cocain
\
Methamphetamine
III. Mot so chat dang duoc diing de cai nghien:
Vien nghien cim ma tuy qudc gia cua Hoa ky (National Institute of Drug Abuse:
NIDA) la mdt ca quan nghien ciiu manh ve cai nghien tren the gidi. Nhieu thudc cai nghien da dugc nghien ciin tdng hgp va iing dung tai day.
Ngudi ta da tim ra nhieu phuong phap cai nghien cho cac loai ma tuy khae nhau. Dudi day la mdt sd thudc cai nghien dugc sir dung nhieu tren the gidi.
- Methadon. Mdt trong nhung thudc cai nghien dugc sir dung nhieu d cac nude phuong Tay la methadon. Methadon la mdt thudc thay thi, tiic la ban than methadon cung gay nghien nhung d miic nh? hon va tac dung gay nghien ciia nd keo dai hon. Moi ngay benh nhan diing mdt Ian vdi lieu phii hgp la se bet cam giac ddi ma tiiy trong ngay. Tuy nhien, qua trinh dieu trj keo dai va nhieu trudng hgp benh nhan lai bj le thudc methadon nhu mdt chdt ma tuy khae [18].
Cdng ty dugc pham Eli Lilly la nha san xuat methadon ldn nhat tren tbi gidi. Ngoai ra cdn cd cac cdng ty nhu Roxane Laboratories, Reckitt & Colman, Du Pont Merck & Sandoz Pharmaceuticals. Cdng ty Eli Lilly san xuat 70% lugng methadon tren thi gidi vdi ten thuang mai la Dolophink hychocloride diing de cai nghien heroin.
- Buprenorpliin. Ia mdt loai thudc de cai nghien nhdm opiat dugc sir dung nhilu [16,17,19, 20]. Hang Essex Pharma dua thudc nay ra thj trudng vdi ten thuong mai la SUBUTEX" dang vien nen 8mg. Hang Schering Plough Pharmaceutical san xudt thudc nay vdi ten thuong mai la Buprenorphine. Hang Reckitt va Colman dua ra thj trudng san phdm Buprenex vdi boat chat la buprenorphine. Buprenex kit hgp dugc tinh chdt cua methadon va naltrexon, khdng gay nghien nhu methadon, de sir dung hon methadon. Buprenorphin cd tinh canh tranh mdt phdn vdi morphin, heroin d thu thi p-opioid (p- opioid agonist) va la chdt ddi khang vdi morphin, heroin d thu thi k-opioid (k-opioid-antagonist). Do tinh chdt hon hgp, vira la agonist vira la la antagonist nay ma buprenorphin dugc sir dung nhilu trong giai ddc cat can va trong dieu trj duy tri benh nhan nghien heroin va methadon. Buprenorphin khdng gay nghien nhu methadon.
- Naltrexon. Naltrexon la mdt chdt ddi khang vdi ma tuy nhdm opiat. Nd duoc sir dung de chdng tai nghien sau khi da sach ma tiiy. Tuy nhien, ngudi ta phai than trgng khi sii'
Tieu ban: Cdc chdt co hogt tinh sinh hoc ISBN: 978-604-913-012-0
dung naltrexon. Ngudi benh khdng dugc vira sir dung naltrexon vira diing ma tiiy (heroin, morphin), vi nhu vay se gay ra phan iing thudc cd the dan den tir vong.
- Naloxon: Naloxon la mdt chat ddi khang ma tuy nhdm opiat. nd cd tac dung loai tru tac dung cua morphin. triet tieu cac bdi chimg cai. Naloxon lam dao nguge hieu qua cua enkephalin va p- endorphin {morphin ndi sinh) trong he mien djch (cu the d te bao diet tu nhien: natural killer NK. Tiiy thudc vao lilu dimg ma naloxon cd tac dung kich thich hay^ kim ham sir phat triln ciia nha bao thdn kinh, (neuroblastoma growth). Naloxon gdn ket vdi te bao
lymphd T trong co thi [22]. Naloxon dugc diing dl chdng tai nghien. Song vi Naloxon la chat doi khang vdi ma tuy nhdm opiat nen phai than trgng, nhdt la khi benh nhan chua sach ma tuy ma lai diing naloxon.
HCI
Methadon hydrochlorid
(Agonist) Buprenorphine
Naloxon
R = -CH2-CH=CH2 Naloxon (Antagonist) R = - H 2 C — < ^ Naltrexon
(Antagonist)
Mdt sd chdt dimg de cai nghiin chinh
IV. Cac thuoc duffc siir dung trong dieu tri cat con nghien ma tuy 6" Viet Nam.
Phac do "An thdn kinh (ATK)"": Tir nhieu nam nay Bd Y te Viet Nam cho phep sir dung phdi hgp cac thudc hudng than (neuroleptic agents) de dieu trj cat con nghien ma tuy cho ngudi nghien tai Viet Nam. Phuang phap dieu trj nay dugc ggi la ""lieu phdp an than kinli" . Phuang phap nay cd nhugc diem la de gay tai bien nhu truy tim mach, gay ao giac met mdi ....Do vay cac bae sy dieu trj phai chii y theo ddi sat cac bieu bien ciia benh nhan khi sir dung cac thudc budng than.
- Methadon. Tir khoang vai nam trd lai day Bd Y te cd chuong trinh tbi diem diing methadon de cai nghien ma tuy. Dau tien la mdt co sd d Hai Phdng va mdt co sd d Ha Ndi dugc thi diem trudc, sau dd rut kinh nghiem va cd md them ca sd d Thanh phd Hd Chi Minh.
Hien nay ciing chua cd danh gia tdng ket ve viec sir dung methadon trong cdng tac cai nghien d Viet Nam. Lieu cd nen va cd the sir dung rdng rai methadon de cai nghien cho ngudi Viet Nam hay khdng thi theo chiing tdi van chua cd cau tra ldi cudi ciing.
Methadon la thudc generic, dugc tdng hgp ldn dau tien tai Ao vao thdi gian chiln tranh thi gidi thir hai. Vao ddu nhung nam 1950 nd dugc sir dung d My de dieu trj benh dau
Hoi nghi Khoa hoc kv niem 35 ndm I 'ten Khoa hoc vd Cong nghe I 'iet Nam - Hd Noi 10 2010
cap tinh. Su dung methadon de cai nghien ma tiiy chinh thirc bat dau tir nam 1965. Cho din nay van cd nhiing cdng trinh nghien ciru tdng hgp methadon dugc cdng bd [23]. Tinh hinh sir dung methadon hien nay dugc tdng quan trong tai lieu [24]. Chuong trinh Hda Dugc cdp nha nude nam 2009 da phe duyet de tai tdng hgp methadon lam thudc cai nghien [25].
- Naltrexon: Naltrexon mdi dugc dua vao thir nghiem diing ban che d Viet Nam.
Thudc nay cd gia thanh tuong ddi cao nen khd dugc sir dimg rdng rai d nude ta.
Cac bai thuoc thao duoc:
- Bdi CEDEMEX: Bai nay do GS. Vu Van Chuyen lam chii da dugc phep sir dung tai cac trung tam cai nghien thudc nganh Lao ddng, Thuang binh va Xa hdi. Tuy iiliien. theo danh gia ciia ngudi sir dung thi gia thanh van hoi cao, lugng thudc dimg cho mdt ldn udng vin ldn qua.
- Bdi thuoc Bong Sen: Bai thudc nay d dang cao ehilt nude do cdng ty Dugc phdm Hau Giang san xuat. Vi la dang ldng nen viec tieu chudn hda, bao quan va van chuyin cd klid khan nhat djnh.
- Bdi thudc Heantos: Bai nay do dng Tran Khudng Dan dua ra ldn ddu tien tir nam 1990 d dang ldng va da dugc Vien Hda hgc, Vien Khoa hgc va Cdng nghe Viet Nam nghien cim cai tien nhieu lan. Bai thudc Heantoss 4 hien nay la san phdm cudi ciing dugc cai tiln vl cdng thirc, quy trinh bao che theo hirdng hien dai va dang dugc Bd Y tl danh gia tinh an toan va hieu qua tren lam sang d giai doan 3. Bai thudc Heantos 4 la ddi tugng nghien cuu cua dk tai khoa hgc cdng nghe nay.
- Cdc bdi thudc khdc: Ngoai cac bai thudc ke tren cdn cd mdt so bai kbac dang dugc nghien cim sir dung nhu bai CAMAG ciia Vien Y Dugc hgc cd truyin Viet Nam do GS. Trdn Thiiy lam chii.
V. Bai thuoc Heantos:
Bai thudc Heantos la mdt bai thudc cd phuong gia giam dugc dng Trdn Khudng Dan suu tam, cai tien diing de giai ddc cat con nghien ma tuy. Bai thuoc nay dugc Bd Y tl Viet Nam nghien cim tinh an toan va hieu luc vao nhirng nam 1989-1990 luc dd vdi cai ten la Heatos va d dang cao ehiet nude ( ldng). Nam 1995, sau khi da nghien ciiu xong giai doan 1 la giai doan tham dd lieu diing, phac dd dieu trj va tinh dung nap ciia thudc thi nhdm nghien cim ciia dng Din da hgp tac vdi Vien Hda hgc, Vien khoa hgc va Cdng nghe Viet Nam ngay nay de tiep tuc nghien ciru cai tien va danh gia lam sang bai thudc nay. Sau khi hgp tac vdi vien Hda hgc. bai thudc dugc ddi ten thanh Heantos va chuyin tir dang ldng ddng chai sang dang ran ddng vien nang cirng.
Thdi gian dau Vien Hda hgc cimg nhdm nghien cim dua ra 3 loai thudc la Heantos 1, Heantos 2, Heantos 3 vdi cac muc dich su dung nhu sau:
- Heantos 1: Diing cat con nghien. giai ddc ma tiiy - Heantos 2: Diing de ho trg gidc ngu trong khi cai - Heantos 3: Dimg de duy tri va chdng tai nghien
Sau nay chuc nang ciia 3 loai thudc nay da dugc gdp lai trong thudc Heantos 4. Thuoc Heantos 4 da dugc giri di kilm nghiem tai CHLB Dire. Phdng tbi nghiem phan tich tdn du va vet thudc Vien Sebastian, Kneipp Forschung dk tiln hanh phan tich va cho bilt kit qua nhu sau:
- Cac kim loai nang sau day dugc djnh lugng va dat tieu chudn chau Au vl ham luong cho phep: Chi. cadimi va thiiy ngan
Tiiu ban: Cdc chdt co hoat tinh sinh hoc ISBN: 978-604-913-012-0
- Dd nhiem khudn: Sd lugng cac loai vi khuan sau day tren mdt don vj khdi lugng thudc da dugc xac djnh va diu ndm trong gidi ban cho phep theo tieu chuan chau Au.
+ Mdm vi sinh vat ua khi d nhiet do thudng + Vi khuan Samonella
+ Vi khuan Escherichia coli + Vi khuan Enterobacteria + Nam
- Tdn du thudc trir sau: Lugng tdn du cac loai thudc trir sau sau day da dugc phan tich va nam trong gidi ban cho phep ciia tieu chuan chau Au:
+ Thudc trir sau gdc co phdt pho + Thudc trir sau gdc co chlor + Thudc trir sau nhdm pyrethroid
+ Thudc trir sau nhdm piperronyl butoxid
- Ddc to aflatoxin (ddc td ciia ndm mdc) : Cac loai aflatoxin sau day da dugc phan tich cd ham lugng nam trong gidi han cho phep ciia tieu chuan chau Au.
+ Aflatoxin Bl + Aflatoxin Gl + Aflatoxin B2 + Aflatoxin G2
- Ve mat hda hgc, bai thudc Heantos 4 da dugc phan tich tai CHLB Dire va khdng tim thay chat nao thudc dien ddc bai va bj cam sir dung cho thudc va thuc pham theo danh muc ciia Chau Au.
- Nam 1997 bai thudc Heantos dugc UNDP tai trg vdi mdt du an cd ten la "Phat trien khoa hgc qudc te bai thudc thao dugc cai nghien ma tiiy Heantos" vdi ma sd VIE96/033.
V.L Nghien ciru tieu chuan hoa bai thuoc Heantos [26]:
Thudc Heantos cd 13 loai dugc lieu trong dd cd 12 loai cd ngudn gdc thuc vat va 1 loai cd ngudn gdc tir ddng vat. Cac loai dugc lieu dugc danh sd tir 1-13. De bao dam rang, chat lugng thudc Heantos d tat ca cac Id san xuat sau nay deu gidng nhau thi can nghien cim phuang phap tieu chuan hda nguyen lieu, san pham trung gian, thanh pham ciing nhu cac quy trinh san xuat, bao che.
- Tiiu chudn hod bdng cdm quan
Cac loai dugc lieu dugc danh gia cam quan ve cac mat nhu kich thudc, mau sdc, miii, vj,
% am theo nhu md ta trong Dugc Dien Viet Nam, xudt ban ldn thii 3, NXB Y bgc. Ha Ndi 2002.
- Tiiu chudn hod bdng phwong phdp quang phd hdng ngogi + Chudn bi mdu:
Can 12 mau dugc lieu cd ngudn gdc thuc vat, da dugc chgn qua phuong phap cam quan, mdi mau 10 gam, xay nhd, ehiet trong bd Soxhiet vdi cdn thuc pham 80% trong 4 gid.
Cat loai dung mdi trong may quay cat chan khdng den khd. 12 mau can djch ehiet thu dugc la
Hoi nghi Khoa hoc ky niem 35 ndm I 'ien Khoa hoc vd Cong nghe Viet Nam - Hd Noi 10 2010
mau de nghien cim tieu chuan boa theo phuang phap phd hdng ngoai va sac ky ldng/ khdi phd HPLC/MS. Dugc lieu thii 13 cd ngudn gdc ddng vat dugc sir dung true tiep de nghien cuu tieu chuan boa ma khdng qua giai doan ehilt xudt.
Phd hdng ngoai dugc ghi tren may IMPACT 410 (FTIR) ciia bang Nicolet, My, trong vimg tir 400 - 4000cm" vdi ky thuat phii hgp vdi mau. Trong trudng hgp ghi dudi dang vien nen trong KBr tbi Img miu trong 800mg KBr khan loai tinh khilt diing cho quang phd dugc nghien deu va ep dudi thiet bj ap suat cao chuyen dung dk tao vien KBr. Trudng hgp ghi dang phim: mdt gigt nhd miu dugc ep giira hai tdm kinh KBr va ghi phd.
- Tiiu chudn hod bdng phuong phdp sdc ky long ghep ndi khdi phd (HPLC/MS).
Mo ta phuong phap
+ Thiit bi vd hod chdt
- He thilt bj: LC/MSD Agilent Series 1100 ciia Vien Hoa hgc, Vien KH va CNVN.
- Can phan tich: Adam AAA 160L - Micropipet loai 1000)al, lOOpl, lOpl - Bdn sieu am
- May quay cat chan khdng
- Cac loai boa chat, dung mdi tinh khilt cho HPLC ciia hang Merck.
Dieu kien phan tich + Cho HPLC:
- Cdt RP 18 (2,1 X 150mm; 5|am) - Tdc do ddng: 0,25ml/ phiit
- Detecto DAD vdi bude sdng 254nm.
- Nhiet do phan tich: Nhiet do phdng - The tich tiem mau: 0,25)il
- Pha ddng: Hdn hgp dung mdi gdm: Kenh A la methanol; kenh B la dung djch nude cd 0,1% axit formic.
+ Cho MS:
- Ngudn Ion: ESI -Nhiet do: 325°C - Tdc do khi: 11 lit/phut
- Nebulizer (ap suat dau phun): 20psi - Chan khdng dn djnh: 253 x 10-5 mbar - Khuyech dai (muhiplier): 1188 volt
- Mau thir: ~lmg dugc boa tan trong hdn hgp MeOH/HiO 6: 4 Ket qua
Vien Hda hgc da thu dugc nhirng ket qua nhu sau:
- Da xay dyng dugc quy trinh chuan san xudt bdt Heantos va quy trinh san xudt thudc Heantos thanh pham. Thudc Heantos dugc san xudt tren day chuyin dat tieu chudn GMP (Thuc hanh san xuat tdt) theo quy djnh ciia td chiic Y tl thi gidi WHO tai Cdng ty CP Dugc pham Nam Ha (Napharco).
Tieu ban: Cdc chdt co hogt linh sinh hoc ISBN: 978-604-913-012-0
- Bdt Heantos va thudc Heantos thanh pham da dugc phan tich. kilm nghiem tai Cdng ty Napharco va trudng dai hgc Y Ha Ndi, ca 2 san pham deu dat tieu chuan co sd (TCCS) va dugc phep diing cho ngudi.
- Da san xuat dugc 20kg bdt Heantos dat tieu chuan va bao cbl thanh 26 kg thudc Heantos (500mg/ vien nang) diing cho nghien cim lam sang giai doan 3 vdi 250 benh nhan tai 3 CO sd la: Benh vien Tam than TWl, Thudng tin, Ha Ndi; Benh vien da klioa tinh Bae Ninh va Trung tam cai nghien sd 1, Ha Ndi.
- Nghien cim lam sang giai doan 3 da ket thiic, dang nghiem thu cap nha nude va xin phep san xuat luu banh.
V.2. Nghien cuu ff ngoai nuffc:
Thuoc Heantos ciing dang dugc nghien cim ve co che tac dung trong cai nghien ma tiiy tai trudng dai hgc University of British Columbia (Canada) bang phuong phap sinh hgc phan tir hien dai.
Trudng dai hgc Essen (CHLB Dire) da tien hanh nghien cim lam sang thudc Heantos tren 60 ngudi Diic nghien heroin tinh nguyen.
Loi cam on:
Xin chan thanh cam on Vien Hda hgc, Vien Khoa hgc va Cdng nghe Viet nam, Bd Y te, Benh vien Tam than trung uong 1, Benh vien da khoa tinh Bae Ninh, Trung tam giao due xa bdi sd 1, Ha Ndi va cac don vj khae trong va ngoai nude da giup dd va img bd chiing tdi trong qua trinh thuc hien de tai nay.
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Hoi nghi Khoa hoc ky- niem 35 ndm \ 'ien Khoa hoc vd Cong nghe \ 'iet Nam - Hd Not 10 2010
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26. Danh muc cdc de tdi thuc hien nam 2009, Chuong trinh phat trien cdng nghe Hoa Dugc cap nha nude. Bd Cdng thuong.
27. Bao cao tdng ket de tai trgng diem cap Vien Khoa hgc va Cdng nghe Viet Nam:
"Nghien ciru tieu chudn hda thudc Heantos, hd trg dieu tri cai nghien ma tiiy", Vien Khoa hgc va Cdng nghe Viet Nam, (2008-2009).
