Mu 11(DHH). Thng tin kt qu nghin cu ti.

THNG TIN KT QU NGHIN CU

1. Thng tin chung:

- Tn ti:
Bo ch gel Pluronic nhy cm bi nhit cha neomycin v panthenol
iu tr tn thng bng trn th th nghim
- M s: DHH2012 - 04 - 15
- Ch nhim ti: Ts. Ds. Trn Hu Dng
Tel: 0944.970.388 E-mail: huudung76@gmail.com
- C quan ch tr ti: Trng i hc Y Dc i hc Hu
- C quan v c nhn phi hp thc hin: Trung tm Kim nghim Thuc, Thc
phm, M phm Tha Thin Hu.
- Thi gian thc hin: 2015 - 2017
2. Mc tiu:
ti c thc hin nhm t 4 mc tiu nghin cu:
- La chn c cng thc ch to gel pluronic cha neomycin v panthenol nhy
cm bi nhit.
- Xc nh c kch ng da ca ch phm trn th th nghim
- Xc nh c n nh ca ch phm theo thi gian bo qun.
- Xc nh c kh nng iu tr tn thng bng ca ch phm trn th th nghim.
3. Tnh mi v sng to:
V tnh mi ca ti trong nghin cu:
y l mt trong nhng ti ln u tin Vit Nam nghin cu s dng vt liu
pluronic F127, mt polymer loi hydrogel c kh nng bin i thun nghch th cht lng
rn bi nhit, to ra mt ch phm gel pluronic nhy cm bi nhit cha neomycin v
panthenol iu tr c cc tn thng bng, m c th l bng nhit III su trn th th
nghim. Nu ch phm trin khai trn lm sng thnh cng, y s l mt trong nhng dc
phm gel tr bng nhy cm bi nhit u tin Vit Nam, nhm tng tnh tin dng cng
nh a dng hn trong vic chn la cc dc phm tr bng bn cnh cc loi hin c trn
tr trng nh mng, da ch, cream...tr bng.
Bn cnh y, vai tr ca micelle v nng ti hn ca micelle (CMC) mt trong
nhng quan nim mi c cng b trong lnh vc Y Dc Vit Nam c minh ho
rt r nt trong bo co khoa hc. Khi cc micelle ny tp trung vi nng ln s
chuyn th cht mi trng t trng thi lng sang trng thi rn vi cu to mng tinh th
bn vng. Tuy nhin y l qu trnh chuyn i thun nghch theo nhit mi trng nn
thng c gi l s thoi bin bi nhit. y chnh l c s l thuyt quan trng
nhm nghin cu ng dng trong k thut bo ch nhm to ra mt ch phm gel pluronic
nhy cm bi nhit c th chuyn i trng thi th cht rn lng khi tip xc vi cc
nhit khc nhau.
 Mu 11(DHH). Thng tin kt qu nghin cu ti.

V tnh sng to ca ti trong nghin cu:

ti ny gp phn to ra mt ch phm gel pluronic nhy cm bi nhit t vt
liu chnh l pluronic F127 phi hp vi cc t dc to cng poly vinylacol, t dc
to tnh kt dnh bn vng povidon S630, t dc gi m propylen glycol, cht bo qun
nipagin cng nh khng sinh neomycin v tc nhn kch thch ti to t bo da panthenol.
Gel pluronic khi dng lng (trong nhit 4 - 80C) c kh nng dn tri u trn vt
thng v to thnh mt lp mng bn vng khi tip xc vi da (nhit 37 0C) va c kh
nng che ph vt thng lm trnh mt dch, cht in gii v chng bi nhim t bn
ngoi, va c kh nng phng thch khng sinh v cht tng sinh nim mc da h tr hiu
qu trong iu tr tn thng bng. V quan trng nht l mng pluronic c th loi b khi
vt thng khi cn thit mt cch d dng hng ngy. Chnh iu ny gii quyt c
nhng hn ch c hu ca loi gel mng pluronic m cc cng trnh nghin cu trc y
gp phi, bi do tnh thn nc ca pluronic nn lp mng to ra khng bn vng v b bo
mn nhanh chng do dch tit trong vt thng bng gy nn. Hn na, mng pluronic khi
p ln vt thng li khng bc ra c d dng, gy bt tin khi s dng trn lm sng.
4. Kt qu nghin cu t c.
xy dng c cng thc bo ch gel pluronic nhy cm bi nhit c cha
neomycin v panthenol.
Cng thc bo ch gel pluronic 20% PF127, 10% PVA, 5% S630, 5% PG, 0,5%
neomycin, 3% panthenol, 0,2% nipagin v nc ct va 100 g. Ch phm gel pluronic
sau khi pha ch trong iu kin v trng c ng trong l nha kn bo qun ni kh
thong nhit 20 - 250C.
Gel pluronic phng thch neomycin rt hiu qu ra mi trng v to c mt s
khng khun ph hp tng t nh kem Flucort-N cha 0,5% neomycin trn th trng
dng lm mu i chng trn mi trng thch dinh dng cy Staphylococcus aureus.
Chng t rng cng thc gel pluronic c xy dng pht huy c tnh sinh kh dng
ca mt ch phm thuc dng ngoi trong in-vitro.
xc nh c kch ng trn da th ca gel pluronic.
Ch phm gel pluronic c bo ch khng cho thy bt k du hiu no trong vic
gy kch ng trn da th th nghim sau 72 gi theo di.
xc nh c n nh ca gel pluronic trong 12 thng bo qun.
Sau 12 thng bo qun trong l nha kn trong iu kin kh thong nhit 20 -
0
25 C, gel pluronic nhy cm bi nhit cha neomycin v panthenol vn m bo yu cu
ca cc tiu ch cht lng c trng, bao gm:
t tiu chun v hnh thc cm quan.
t tiu chun v ng nht.
t tiu chun v gi tr pH.
t tiu chun v kh nng nhy cm bi nhit.
t tiu chun kh nng dn mng v loi b trn tm knh.
t tiu chun v gii hn nhim khun.
t tiu chun v hm lng neomycin trong ch phm.
 Mu 11(DHH). Thng tin kt qu nghin cu ti.

nh gi c kh nng tr liu ca gel pluronic trn th th nghim c gy

bng nhit III su.
Trn cc vt thng bng nhit III su, nhm th c iu tr bng gel pluronic
cha neomycin v panthenol c tc tin trin lnh ho vt thng tt v lm lin so vt
thng sau 14 ngy iu tr, nhanh hn nhiu so vi nhm khng c tr liu. Thnh cng
ca th nghim trn ng vt th nghim trong in-vivo ny l rt quan trng, nhm nh
hng cho cc th nghim lm sng (clinical trial) tip theo trn bnh nhn bng.
5. Sn phm
Danh mc sn phm, s lng v yu cu khoa hc t c
Stt Tn sn phm S lng Yu cu khoa hc
1 o to Dc s i hc 02 Dc s i hc
2 Bo trong nc 02 Tp ch chuyn ngnh ISSN
3 L ng gel pluronic nhy cm bi 10 t tiu chun nh TCCL
nhit cha neomycin v panthenol xy dng.

4 Bo co tng hp ti 01 t yu cu v tnh khoa hc

6. Hiu qu, phng thc chuyn giao kt qu nghin cu v kh nng p dng

y l mt ti mang tnh cng ngh v c nh hng ng dng. Tuy cha tnh
c hiu qu trong thng mi ho sn phm nhng cc kt qu ti t c s l cc
c s khoa hc quan trng, nhm nh hng cho cc th nghim lm sng (clinical trial)
tip theo trn bnh nhn bng. Nu trin khai trn lm sng thnh cng, y s l mt trong
nhng dc phm gel tr bng nhy cm bi nhit u tin Vit Nam, nhm tng tnh tin
dng cng nh a dng hn trong vic chn la cc dc phm tr bng bn cnh cc loi
hin c trn tr trng nh mng, da ch, cream...tr bng.
Tha Thin Hu, ngy 7 thng 5 nm 2013
C quan ch tr Ch nhim ti
(k, h v tn, ng du)

TS. Trn Hu Dng

Ch : Trong mc 4, ghi r nhng kt qu chnh mt cch c th t c t vic thc hin

ti. Khng ghi s lng cc bi bo ng ti v s NCS hng dn vo mc ny.
 Mu 11(DHH). Thng tin kt qu nghin cu ti.

INFORMATION ON RESEARCH RESULTS

1. General information:
Project title: Preparation of cholesteryl dendimer G5 film as a carrierfor the local
prolonged metronidazole release on mice
Code number: DHH2012 - 04 - 15
Coordinator: Tran Huu Dung, Ph.D., Pharm.
Implementing institution: College of Medicine and Pharmacy, Hue University
Cooperating institution(s): Le Chuyen, Ph.D.,Med., Department of Pharmacology, College
of Medicine and Pharmacy, Hue University. Tran Thanh Phuoc, Ms., Dent., Faculty of
Dentistry, College of Medicine and Pharmacy, Hue University
Duration: from 2011 to 2014
2. Objective(s):
Study was carried out aimed to prepare the cholesteryl dendrimer G5 film as a carrier
for the local prolonged metronidazole release orienting for the application in the
periodontal treatment effectively and safely.
3. Creativeness and innovativeness:
This is one of the first projects in Vietnam studied on the of hydrophobic cholesteryl
dendrimer polymers and used these materials for the preparation of thin films as carriers
containing metronidazole which could control the local antibiotic extended release in a long
time (4-5 days), the necessary time to ensure periodontal treatment effectively and safely.
4. Research results:
Cholesteryl dendrimer conjugates were prepared and determined structure by FT-IR
and 1H-NMR spectra, the density of cholesterol units conjugated on cholesteryl dendrimer
by colorimetric method, investigated surface morphology by SEM. Research result showed
having a stable conjugation of cholesterols on dendrimer surface, and the increase of
conjugated cholesterol units induced the change of solubility and surface characteristics of
cholesteryl dendrimer.
Cholesteryl dendrimer containing 2; 5; 10% metronidazol were prepared on the thin
aluminum discs and applied for the investigation of erosion, drug release profiles in in-vitro
and in-vivo and effect of environmental pH and viscosity factors also. The prepared films
were flatten cylindrical shape, diameter 2 - 3 mm, thickness 0.5 - 0.7 mm, weight 5 0.5
mg. Film property is durable, flexible, pale yellow color with surface intact. The
investigated result showed the film erosion was decreased while the drug release profile
was prolonged following the increase of hyddrophobic cholesterol density on the dendrimer
surface. Particularly, the cholesteryl dendrimer film 1/10 extended the erosion time as the
drug release control until 4 days, the suitable time for the design of a carrier sustaining drug
release applying for periodontal treatment.
Furthermore, the film erosion and drug release rate were effected by environmental
viscosity and pH condition. After determined non acute toxicity by LD50 test on mice,
cholesteryl dendrimer film 1/5 containing 5% metronidazole was chosen for in-vivo studies
 Mu 11(DHH). Thng tin kt qu nghin cu ti.

on rat dorsal. The investigated result showed there was a film erosion faster than in-vitro
test, however the drug release profile was sustained after 3 days.
Simultaneously, from the observation on the rat dorsal epidermal tissue inserted
polymer film showed the wounds were dry and healing continuously. This is an important
scientific basis for the clinical trials subsequently, in order to design a polymer carrier
containing drug applying for periodontal disease and some local specific treatments
sufficiently and safety.
5. Products:
- The final report of the study
- The summary of the study
- 2 papers published in the Journal of Pharmacy
- 3 undergraduate thesis of pharmacy
6. Effects, transfer alternatives of research results and applicability
This is an applied study, but the content was limited in the researches of in-vitro and
in-vivo so that there have not evaluated for the transfer and application of research results.
However, with the obtained results above will be a preliminary scientific basis for our team
suggesting a recommendation for the clinical trials further on periodontitis volunteers to
design a cholesteryl dendrimer film containing metronidazole for the periodontal treatment
sufficiently.
Hue, April 22, 2013
Implementing institution Correspondent author