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ADVATAME GVHD: Nguyn Th Hong Yn

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MC LC

MC LC .......................................................................................................................... 1

LI M U .................................................................................................................... 2

I. TNG QUT V ADVANTAME ............................................................................... 3

1. Khi nim .................................................................................................................... 3

2. Lch s ra i ............................................................................................................... 3

3. Cng thc cu to ........................................................................................................ 5

4. Tnh cht vt l v ho hc .......................................................................................... 5

5. Phng thc sn xut .................................................................................................. 7

6. ng dng ..................................................................................................................... 7

II. VAI TR V C CH CA ADVANTAME ........................................................ 10

III. C TNH ................................................................................................................ 10

IV. QUI INH S DNG............................................................................................... 11

TI LIU THAM KHO ............................................................................................... 13


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LI M U

Ph gia c s dng trong thc phm t rt lu i. T thi tin s con ngi

bit phn bit ci g mn ci g ngt. ri h nm vo thc n khi nu nng. Ngy

nay vi s pht trin khng ngng ca khoa hc k thut, con ngi ngy cng mun n

ngon, nhng cng phi nhanh v gn.

H n qu nhiu n nhanh v nhng n vt c v ngt. Do , t l bo ph

trn th gii ngy cng tng v c bit l la tui t 10 15. c th p ng c

s thch n ngt ca hu ht mi ngi nhng vn khng lm nh hng n sc kho th

cc nh sn xut thc phm bt u nghin cu cc cht to ngt nhng khng c gi

tr dinh dng.

Nhng nhng cht chit xut t t nhin th qu mc v qu t nn khng p

ng nhu cu ca ngi tiu dng. Cn cc cht tng hp th li d gy ra nhng bnh

mn tnh cho ngi s dng. ng trc tnh hung , cc nh sn xut buc phi tm

cch kt hp hi ho c hai yu t . chnh l l do m Advantame ra i.

Em xin c cm n c Nguyn th Hong Yn trong thi gian qua truyn t

v cng c cho em mt kin thc y v ph gia thc phm. D em c gng ht

sc nhng do kin thc v nhng hiu bit ca em cn gii hn nn bi tiu lun vn cn

nhiu ch sai st. Em rt mong c thng cm v hng dn ch bo thm gip em

hon thin bi tt hn.


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I. TNG QUAN V ADVANTAME.

1.Khi nim:[2], [3], [8]

Advantame l mt cht lm ngt siu cao tim nng mi v tng hng v c

pht trin bi Ajinomoto. N c ngun gc t aspartame, mt cht lm ngt dipeptit gm

acid aspartic v phenylalanine, v vani. Advantame ngt khong 20.000 ln so vi ng

v ngt hn aspartame 100 ln. Advantame khng cung cp nng lng, n c ngt v

hng v ging nh ng v khng li mi v khng mong mun. l tnh cht

quan trng trong mt lnh vc v thc phm v ung, n ph hp nht s dng

trong vic phi trn vi nhng cht to ngt khc c ngt cao hoc carbohydrate.

Advantame n nh nht khi dng bt kh. Trong cc thc phm dng dung dch

nc, s n nh ca n th tng t nh aspartame nhng s n nh vn c gi vng

pH cao hn, cng nh iu kin nhit cao hn (v d, nng v cc qu trnh ko

di si m khc), v trong sa chua.

Kt qu ca nhiu nghin cu xc nhn rng an ton advantame l an ton s

dng bi ngi tiu dng ni chung v c bit l cho nhng ngi c bnh tiu ng

ni ring.

Advantame mi c cng b trong FAO JECFA Monographs 14 (2013). Bn

cnh , Advantame cng c FDA cng b cho php s dng trong thc phm nh

mt cht lm tng v ngt v hng v cho sn phm, tr tht v gia cm. Ngoi ra

Advantame cng c FEMA GRAS ph duyt s dng trong sa, trng ming

ng lnh, ung v ko cao su. Advantame c ch s INS 969, C.A.S. 714229206,

ANS9801, FEMA 4716.

2. Lch s ra i: [3], [9], [10]

Advantame l kt qu ca mt chng trnh nghin cu di hn ti Ajinomoto

khm ph nhng cht to ngt c tim nng cao mi vi hng v c trng mong mun.

Mc ch l khm ph cc phn t to ngt aspartyl mi da trn da trn chin lc

sau y:

La chn cc hp cht chnh.

Ti u ho vic qun l cc hp cht v nghin cu cch hot ng ca n.

S dng m hnh phn t trn my tnh.

Tng hp cc hp cht trn v hnh thnh cc cht to ngt tim nng mi.

Chng trnh nghin cu ny tin b nh cc lnh vc nghin cu v v ngt, bt

u vi Schallenberger v m hnh Acree ca "AH-B" (Shallenberger 1996;. Eggers v

cng s 2000) v m hnh xut Ariyoshi cho cc dn xut aspartame (Ariyoshi 1976)

vi gi thuyt ca s tng tc gia cc peptide to ngt v vic cm nhn v ngt ca c


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th. iu ny bao gm vic s dng cc tnh ton trong ho hc phn tch cu trc ca

cc phn t to ngt v pht trin cc m hnh phn t to ngt cho n vic xc nh cc

th th cm nhn v ngt ca ca c th (Hoon v cng s nm 1999;.. Kitagawa v cng

s nm 2001; Li v cng s. 2001, 2002;. Max v cng s nm 2001;. Nelson v cng s

nm 2001;. Sainz v cng s nm 2001;. Zhao v cng s 2003). S sng lc u tin ca

cc ng c vin c da trn tim nng to ngt, cht lng hng v, v s c li ca

cc cht tng hp ny. Vic sng lc ban u lm gim cc ng c vin t hng trm

cc hp cht n ch cn li khong mi hp cht. Ln th hai kim tra cht ch hn

da trn cc tiu ch sau: tim nng to ngt ngo, chi tit v hng v ca tng cht, tnh

cht vt l-ha hc, tnh kh thi trong sn xut cng nghip v d tnh ng lc trao i

cht trong c th con ngi bng vic th trong ng nghim kho nghim

V kt qu ca qu trnh ny l mt cht lm ngt mi l, N-[N-[3 - (3-hydroxy-4-

metoxyphenyl) propyl]-a-aspartyl]-L-phenylalanine 1-methyl ester monohydrat (ban u

c tn m l ANS9801 nhng by gi c gi vi tn advantame, cng thc phn t:

C24H30N207.H20, CAS No. 714229-20-6). N c mt im ch th v l advantame

c mt s tng ng v cu trc i vi cc cht to ngt t nhin, v d nh nhm 3-

hydroxy-4-metoxyphenyl tn ti trong phyllodulcin, mt cht lm ngt c tm thy

trong l ca Hydrangea serrata (Hydrangeaceae) (Ujihara vi cc ng nghip. 1995) v

dihydrochalcone neohesperidin, mt cht lm ngt c ngun gc t s hydro ca

flavanone neohesperidin, c tm thy trong tri cy h cam qut (Horowitz v Gentili

1961, 1963a, 1963b, 1969; Horowitz 1964).


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Hnh 1.2.1: Mi tng ng gia Advantame vi cc cht ngt t nhin

3. Cng thc cu to: [3], [8], [10]

- Tn gi theo IUPAC: N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]--

aspartyl]-L-phenylalanine 1-methyl ester, monohydrate.

- Tn gi theo CA: L-phenylalanine, N-[3-(3-hydroxy-4-methoxyphenyl)

propyl]-L- alpha-aspartyl-, 2-methyl ester, monohydrate.

- Cng thc phn t: C24H30N2O7.H2O.

- Cng thc cu to:

4. Tnh cht vt l v ho hc: [2], [3], [8]

- Advantame c khi lng phn t l 476.52 g/mol v c nhit nng chy l

101.5C.

- Advantame thng dng bt mu vng. Loi bt thng c s dng c

thnh phn phn trm ca Advantame t 97.0% n 102.0% trn khi lng cht khan.

- n nh ca Advantame ph thuc rt nhiu vo cc iu kin mi trng

nh nhit , pH, p sut.

- Advantame rt t tan trong nc, t tan trong ethanol v tan s tng ln khi gia

nhit trong qu trnh ho tan.

Bng 1.4.1: tan ca Advantame sau 30 pht ti cc nhit khc nhau trong

nc, ethyl acetate v ethanol.

tan ca Advantame trong nc, ethyl acetate, ethanol sau 30 pht

Nhit (0C) tan ca Advantame (g/100ml dung mi)

Nc Ethanol Ethyl acetate

12 0.076 0.798 0.165

25 0.099 1.358 0.279

40 0.210 3.827 0.796

50 0.310 9.868 1.600

60 0.586 32.277 2.271


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- Yu cu v tinh khit ca Advantame c th hin trong bn sau:

Bng 1.4.2: Cc yu cu c bn v sn phm Advantame

Specification Parameter Specification Value Analytical Methodology Purity Assay Not less than 97.0% and not

more than 102.0% on anhydrous basis

HPLC internal standard method

Specific rotation [a] 20

D Between -450

and -380 Japanese Pharmacopeia

method Advantame-acid Not more than 1.0% HPLC method Total other related substances

Not more than 1.5% HPLC method Water Between 2.5 and 5.0% Karl Fischer

coulometric titration Residue on ignition Not more than 0.2% Japanese Pharmacopeia

method Total Heavy Metals (mg/kg) Not more than 10 Japanese Pharmacopeia

method Lead (mg/kg) Not more than 1 Atomic absorption Arsenic (mg/kg) Not more than 2 Japanese

Pharmacopeia method Residual Solvents (mg/kg) Methyl Acetate Not more than 500 Gas chromatography Isopropyl Acetate Not more than 2,000 Gas chromatography Methanol Not more than 500 Gas chromatography 2-Propanol Not more than 500 Gas chromatography Microbiological Contaminants Bacteria count Not more than 20 CFU/g Japanese Pharmacopeia

method Fungi Not more than 10 CFU/g Japanese Pharmacopeia

method Pseudomonas aeruginosa Negative Japanese Pharmacopeia

method


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5. Phng thc sn xut: [1], [2], [3], [6]

Advantame c tng hp t Aspartame v 3 - (3-hydroxy-4-metoxyphenyl) -

propionaldehyde (HMPA) trong mt qu trnh mt bc bng cch kh N-alkyl ha,

c thc hin bng cch x l Aspartame v aldehyde vi hydro trong s hin din ca

mt cht xc tc nh l bch kim (Pt / C) trong dung dch methanol. Nhit c nng

ln v kt qu l hp cht tri qua kh N-alkyl ha sn xut Advantame. Hn hp

phn ng c lc loi b cc cht xc tc phn ng v tp trung gim p lc. trch

xut cc Advantame t dch lc cn li, methanol v isopropyl acetate c thm vo v

nhit gim xung kt tinh cc Advantame, sau ly ra v tinh luyn li to ra

hp cht c tinh khit theo yu cu. HMPA c ngun gc t vanillin v c tng hp

theo bn bc sau y.

Hnh 1.5.1: Qu trnh sn xut Advantame

6. ng dng: [1], [2], [3]

- V tim nng to ngt ng ch ca advantame, nn n c s dng trong

cc sn phm thc phm v nc gii kht nng thp hn nhiu so vi cc cht to

ngt c tim nng cao khc. Dau y l bng lit k mt s c tnh nng s dng ca

advantame trong thc phm v ung khc nhau khi s dng advantame nh cht lm

ngt duy nht.


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Bng 1.6.1: Hm lng Advantame d kin trong thc phm v ung

- Advantame c c tnh rt th v nh mt cht tng cng hng v. nh gi

chc nng ny, advantame cn phi c kim tra vi cc cht cng c kh nng tng

cng hng v ngt nhng di mc ca n. Th nghim ban u l xc nh cc

mc c im bt u khc nhau (GDTL) ca advantame, v sau tin hnh th

nghim xem kh nng tng cng hng v ca advantame bng hoc thp hn GDTL.

Bng 1.6.2: Kh nng tng cng hng v ca Advantame trong nc gii kht

hng du. GDTL bng 1.46ppm.

Sn phm p dng Nng ca Advantame

Nc ung c gas 4 10 ppm

ung rt nng 3 4 ppm

Ko cao su 100 400 ppm

Sa chua 4 7 ppm

Bnh bng lan 10 18 ppm


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Bng 1.6.3: Kh nng tng cng hng v ca Advantame trong sa chua v vani.

GDTL bng 0.92 ppm.

Bng 1.6.4: Kh nng tng cng hng v ca Advantame trong ko cao su hng

bc h. GDTL trn 40 ppm.


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- c ng dng nh cht lm ngt thay th: v ngt c trng advantame c s

dng trong cng ngh thc phm thay th mt phn cc cht lm ngt c carbohydrate

nh ng hoc fructose, corn syrup, trong khi vn duy tr c hng v ban u ca

sn phm v ngi tiu dng khng th phn bit c vi sn phm 100% cht ngt

carbohydrate Nghin cu c din ra trong ni b v s dng php th tam gic vi cc

chuyn gia v cng thc ung khc nhau nh cola, cam v chanh l nhng hng v

ca nc gii kht c gas; v nc p tri cy, nc chanh, tr chanh v chanh l nhng

hng v ca nc gii kht khng c gas, nhng v d trn cho thy rngvic s dng

advantame ph thuc vo cng thc to thnh sn phm v 40% cht lm ngt c th

c thay th bng advantame m khng thay i hng v. Thng advantame c th

thay th t 20% n 30% v ngt trong hu ht cc sn phm m khng thay i hng v

c trng ca sn phm . S dng advantame thay th ng hoc fructose, corn

syrup s lm gim lng ng, lng calo, v chi ph sn xut ra sn phm. Advantame

cng c th c s dng thay th mt phn ca cht lm ngt c hiu lc cao khc

trong khi vn duy tr c hng v tng t hoc trong mt s trng hp n cn c th

ci thin hng v tng th v tng cng hng v cho sn phm. Ni chung l mc

thay th c th c thc hin vi advantame khi thay th cc cht lm ngt hiu lc cao

khc, ln hn mc m c th c thc hin khi thay th cc cht lm ngt carbohydrate.

Thay th mt phn ca cht lm ngt hiu lc cao cng c th c thc hin trong khi

gim chi ph, v trong nhiu trng hp cng ci thin hng v.

II. VAI TR V C CH CA ADVANTAME.

- Advantame c tng hp t HMPA v aspartame. Do aspartame cng lm mt

cht to ngt tng hp cn HMPA th c tng hp t vani mt cht ngt t nhin nn

ngt ca advantame gp rt nhiu ln so vi tng cht trn.

- Khi s dng advantame trong thc phm, th ngi tiu dng s cm nhn ngay

c v ngt do c gc vani l cht ngt t nhin. ng thi bn cnh do c gc

aspartame nn d v ngt ca advantame cng c duy tr rt lu v con lu hn c d

v ca aspartame. Ngoi ra advantame khng c hng v hoc mu sc khng mong

mun nn d dng p dng cho hu ht cc sn phm thc phm.

III. C TNH. [1], [2], [3], [4], [5], [7]

- S an ton ca advantame c nh gi trong mt s lng ln cc nghin

cu tin hnh chut, chut, th, ch v con ngi di tt phng th nghim thc hnh

(GLP) v bao gm tt c nhng khuyn co trong Sch ca FDA Hoa K (US FDA

2000). i vi mi ca nhng nghin cu quan trng, mt nghin cu khng GLP s b

c thc hin xc nh c liu tm thch hp c s dng


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- Advantame c chng minh cho thy l khng gy t bin trong mt xt

nghim Ames khi vi cc chng khc nhau ca Salmonella typhimurium, c hoc

khng kch hot trao i cht. N cng tng t khi khng th hin bt k tim nng

gy t bin no th hin bu c ra ngoi trong kho th nghim trn chut . Khng c

tim nng gy ng c c chng minh chut khi tin hnh th nghim advantame

c dng cho nhng con chut bng cch a thc n theo ng ming.

- Advantame n nhanh chng b thy phn ng tiu ha vi acid tng ng.

Ch mt phn nh ca advantame hoc axit tng ng c hp th t trong lng ca

ng tiu ha v khong 87% -93% s c bi tit trong phn v phn cn li c bi

tit trong nc tiu v acid tng ng th cng c c ch tng t. Khng c duy tr m

c th no ca advantame hoc acid tng ng. Hai nghin cu lm sng v kh nng

dung np ca advantame ngi, bao gm c nhng i tng bnh thng v nhng

i tng b bnh tiu ng c tin hnh. Bao gm nhng nghin cu v liu dc

duy nht, nghin cu liu leo thang nam gii khe mnh, mt nghin cu an ton 4

tun v kh nng dung np advantame hoc acid tng ng nam gii khe mnh, v

mt nghin cu an ton 12 tun bnh nhn tiu ng. Tiu th mt liu duy nht

advantame ln n 0,5 mg / kg trng lng c th / ngy c chng minh l an ton

trong c hai i tng ngi bnh thng v bnh nhn tiu ng. Khng c tc dng

ph c hi c bo co li trong bt k nghin cu no con ngi v advantame

khng c nh hng trn ng huyt hoc insulin nhng ngi bnh thng v cng

khng c nh hng trn s dung np glucose hoc khng insulin bnh nhn tiu

ng.

IV. QUI NH S DNG. [1], [2], [3], [4]

-Advantame l mt ph gia cn rt mi i vi th trng sn xut thc phm hin

nay.

- GRASS cho php s dng Advantame vo trong mt s n phm thc phm

nhng vi nng rt thp. iu c th hin trong bng sau.

Bng 4.1: Nng Advantame cho php s dng trong mt s sn phm thc phm

Sn phm Nng Advantame

ung khng cn 1.5 ppm Ko cao su 50 ppm Cc sn phm sa (dng lng) 1.0 ppm Cc sn phm sa ng lnh 1.0 ppm


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- Advantame c FAO thng qua v a vo danh mc cc cht ph gia c

php s dng trong thc phm vo nm 2013. ng thi, n cng mi va c FDA

chp nhn cho php s dng M.

- ADI = 0-5mg/kg.


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TI LIU THAM KHO [1] Prepared by Ivan Stankovic, Ph.D. and reviewed by Daniel E Folmer, Ph.D.,

Chemical and Technical Assessment, Food and Agriculture Organization.

[2] Rick and Technical Assessment Report, Supporting Document 1, FOOD STANDARDS Australia New Zealand.

[3] Lyn OBrien Nabors, Alternative Sweetener, Fourth Edition, CRC Press Taylor & Francis Group, 2012.

[4] Who Food Additives Series 68: Safety Evaluation of Certain Food Additives and Contaminants, Prepared by the Seventy-seventh meeting of the Joint FAO/WHO.

[5] Food and Chemical Toxicology 49, S70-S76, 2011.

[6] 21CFR Part 172, Food and Drug Administration.

[7] How Sweet It Is: All About Sugar Substitutes, Consumer Health Information, Food and Drug Administration.

[8] Advantame (Tentative), 77th JECFA, Food and Agriculture Organization, 2013.

[9] http://www.advantame.com/

[10] http://en.wikipedia.org/wiki/Advantame

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