• Polymer(Korea)
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• v.39 no.3
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• pp.480-486
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• 2015

The adhesion of tissue and organ occur with frequency after surgery. Theomosensitive hydrogel was prepared from poloxamer/chitosan/epidermal growth factor as adhesion barrier agent. The prepared hydrogel showed sol-gel transition temperatures around human temperature and gelation temperature was the faster within 1 min. The hydrogel sustained the release of epidermal grow factor during 7 days. The hydrogel was highly effective for the prevention of tissue and organ adhesion in rat model. The thermosensitive and antibacterial chitosan hydrogel can be useful to consider the anti-adhesion barrier with increased adhesion of organ and sustained release of epidermal growth factor.

• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.21-28
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• 2003

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT $pK_{a}$ 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of $Labrasol^{\circledR},\;Transcutol^{\circledR}$, oleic acid and l-menthol. In the accelerated stability test(25, 40 and $50{\circ}C$), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.409-415
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• 2013

We attempted to determine the action target of Shiitake mushroom extract with a known anti-hyperlipidemic effect in poloxamer(P) 407-induced hyperlipidemia model. We investigated the anti-hyperlipidemic effects of the water extract from Shiitake mushroom on the progress of high fat diet for 4 weeks. Experimental rats were divided into 5 different experimental groups including an normal group (normal diet; n=10), control group (hyperlipidemia; n=10), Experimental group I (hyperlipidemic rats treated with Shiitake mushroom extract (100 mg/kg, PO), n=10), Experimental group II (hyperlipidemic rats treated with Shiitake mushroom extract (300 mg/kg, PO), n=10), and Experimental group III (hyperlipidemic rats treated with Shiitake mushroom extract (500 mg/kg, PO), n=10). It is to analysis changes in body weight, visceral fat weight, blood lipid profiles, HMG-CoA reductase and histological findings. Body weight and epididymal fat weight was not significantly change in experimental groups (p>0.05). The level of total cholesterol, TG, arthrogenic index, and HMG-CoA reductase were significantly lower in experimental groups than control group (p<0.05). These results suggested that the Shiitake mushroom extract administration may act by inhibitory the release of cholesterol related factors and HMG-CoA from the hepatocyte without liver and kidney cell damage in hyperlipidemia rats.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.233-241
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• 2005

Ursolic acid (UA), a bioactive triterpene acid, has been known to increase collagen content in human skin in addition to other actions such as anti-inflammatory, skin-tumor prevention and anti-invasion. However, it is poorly soluble in water. Therefore, we firstly prepared microemulsion system with benzyl alcohol, ethanol and Cremophor EL, RH 40 and Brij 35 as surfactant in order to increase solubility of UA and then prepared microemulsion was dispersed in o/w cream base for the topical delivery of UA in an effort to improve anti-wrinkle effect. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using benzyl alcohol as an oil, Cremophor EL, RH 40 and Brij 35 as a surfactant. The droplet size of microemulsions was characterized by dynamic light scattering. The accumulation of VA in the skin from topical cream was evaluated in vitro using hairless mouse skins. The mean droplet size was $26.8{\pm}6.6$ nm for microemulsions II with Cremophor EL. All UA creams showed pseudoplastic flow and hysterisis loop in their rheogram, depending on the type of materials added in topical creams. The in vitro accumulation data demonstrated the UA topical cream prepared with the combination of Poloxamer 407 and Xanthan gum as a copolymer showed higher accumulation percentage than those prepared with either Poloxamer 407 or Xanthan gum. These results suggest that UA topical cream using microemulsion systems may be promising for the topical delivery of UA.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.33-38
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• 2005

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel, cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.219-240
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• 2006

Objective : This experimental study was designed to determine the anti-obestic effects of Bangpoongtongsungcankamibang(BTSK). Method : In vitro, BTSK extracts of various concentration (50,100, 200 $200{\mu}g/ml$)were added examination. The protein and mRNA expression of $C/EBP{\alpha}$ and $PPAR{\gamma}$ receptor was measured by western blot assay and RT-PCR. In vivo, BTSK extracts of various concentration (100, $200{\mu}g/ml$) were orally administered to induced hyperlipidemic rats by poloxamer-407 for consecutive four weeks and serum triglyceride, total cholesterol were measured. This method applied to induced hyperlipidemic rats by triton WR-1339, too. Obesity induced rats by the high fat-diet for six weeks were orally administered BTSK extracts of various concentration (100, $200{\mu}g/ml$) and serum triglyceride, total cholesterol, LDL-cholesterol, triglyceride, LDL-cholesterol, triglyceride, HDL-cholesterol, hydroxy radical, superoxide dismuatse activity were measured. Results : I. In vitro 1. The 3T3-L1 cells' differentiation was significantly decreased by BTSK. 2. expression of $C/EBP{\alpha}$ and $PPAR{\gamma}$ was was significantly decreased by BTSK. II. In vitro 1. BTSK significantly reduced serum triglyceride, total cholesterol, contents in poloxamer-407 treated rat. 2. BTSK significantly reduced serum triglyceride, contents in Triton WR-1339 treated rat. But Total cholesterol did not show a significant change. 3. BTSK significantly reduced body weight gain of rat and adipose tissue mass of rats and serum triglyceride, LDL-cholesterol, contents and significantly increased HDL-cholesterol, HTR(HDL-cholesterol/Total-cholesterol) in rats with obesity induced by the high fat-diet. 4. BTSK reduced blood lipid peroxide, hydroxy radical and increased superoxied dismuatse(SOD) activity.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.249-255
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• 2009

The main object of this study was to prepare of w/o emulsion including glyceryl monooleate(GMO) and to evaluate its stability by using the recently developed $Turbiscan^{(R)}LAB$. GMO is the polar oily surfactant with the low HLB value, and it forms the gel phase of cubic structures after dissolves in aqueous media. Phosphate buffer solution (PBS) of pH 7.4 was prepared as the water phase and Marcol 52(mineral oil) was used as the oil phase in this study. GMO was used as the surfactant of W/O emulsion. W/O emulsion using GMO alone as a surfactant was very unstable. But the emulsion using both GMO and poloxamer 407 was more stable. The stability of W/O emulsions was evaluated after centrifuging the emulsions. But it was difficult with naked eye because an opaque and concentrated system like W/O emulsion was very turbid. So $Turbiscan^{(R)}LAB$ was used to detect the destabilization phenomena in non-diluted emulsion. As a result, the W/O emulsion using the proper amounts of GMO and poloxamer 407 was more stable among them using GMO of various amounts. But it seems that the other element for the stability of W/O emulsion including GMO was required. Furthermore, the $Turbiscan^{(R)}LAB$ was a very efficient analyzer for evaluating the physical stability of emulsion.

• Journal of Pharmaceutical Investigation
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• v.38 no.6
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• pp.393-398
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• 2008

A propofol delivery system was prepared using two biocompatible polymeric surfactants, poloxamer 407 and PEG 400. The nanoparticular stability of the micellar system was evaluated in terms of temperature change, storage time and composition. The particle size of the system was slightly increased with elevating temperature from $4^{\circ}C$ to $25^{\circ}C$, but its distribution was unimodal. At $40^{\circ}C$, the system presented a bimodal particle size distribution and the increase in the fraction of particles larger than 15 nm. This result might be due to the expansion of the nanoparticles through micellar swelling at the high temperature. It was found that propofol was gradually come out of the system, stored for a month at three different temperatures (4, 25 and $40^{\circ}C$). The drug loss was apparently dependent on temperature and the system composition. Increasing temperature induced the acceleration of the drug loss of $7{\sim}10%$ at $4^{\circ}C$ and $14{\sim}16 %$ at $40^{\circ}C$. This may be owing to the high diffusivity resulting from the swelling of the hydrophilic surface of the nanoparticle at high temperature. However, the addition of PEG 400 to the system led to the reduction of the drug loss. This result is associated with the previous investigation that PEG coverage decreased diffusion coefficient because of the formation of the denser structure on the surface of nanoparticulate. Nevertheless, the limited amount of PEG, less than 2% (w/v), should be used to prevent the precipitation and discoloration of the system.

• YAKHAK HOEJI
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• v.51 no.1
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• pp.56-62
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• 2007

Twelve epoxy and hydroxydiosgenin derivatives (DI-1${\sim}$DI-12) were synthesized from diosgenin (25(R)-5-spirosten-3${\beta}$-ol). Diosgenin was epoxidized with m-chloroperoxybenzoic acid (mCPBA) to oxidize 25(R)-4${\alpha}$,5${\alpha}$-epoxyspirostane (DI-1). Diosgenin was reacted with DDQ to form 25(R)-1,4,6-spirostatrien-3-one (DI-2), which was treated with 30% H$_2$O$_2$ to give 25(R)-1${\alpha}$,2${\alpha}$-epoxy-4,6-spirostadien-3-one (DI-3) and treated with mCPBA to form 25(R)-6${\alpha}$,7${\alpha}$-epoxy-1,4-spirostadien-3-one (DI-7), respectively. DI-3 was reduced with NaBH$_4$ to afford 25(R) -1${\alpha}$,2 ${\alpha}$-epoxy-4,6-spirostadien-3${\beta}$-ol(DI-4) and reacted with Li metal in absolute ethanol to form 25(R)-2-ethoxy-1,4,6-spirostatrien-3-one (DI-5). DI-7 was reduced with NaBH$_4$ to produce 25(R)-3${\beta}$,7${\alpha}$-dihydroxy-4-spirostene (DI-8) and treated with Li metal in liquid ammonia to produce 25(R)-7${\alpha}$-hydroxy-4-spirosten-3-one (DI-9). DI-2 was reduced with NaBH$_4$ to form 25(R) -4,6-spirestadien-3${\beta}$-ol(DI-10), which was stirred with 30% H$_2$O$_2$ to synthesize 25(R)-4,6-spirostadien-3-one (DI-11) and reacted with mCPBA to give 25(R)-4${\beta}$,5${\beta}$ -epoxy-6-spirosten-3${\beta}$-ol (DI-12), respectively. The antinociceptive effects of synthesiz ed compounds were measured by hot plate method and compound DI-7 signifcantly exhibited antinociceptive effect. DI-2 decreased the serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.

• Polymer(Korea)
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• v.37 no.4
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• pp.442-448
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• 2013

In this study, we developed and optimized hydrophilic polymer-based solid dispersion formulations (SDs) using a spray drying method for improving the aqueous solubility of eprosartan, one of poorly soluble drugs that has been broadly used for the treatment of high blood pressure. Hydroxylpropylcellulose (HPC) and poly(vinyl pyrrolidone) (PVP) were used as hydrophilic polymer matrices and poloxamer 407 (P407) added as a polymeric surfactant. Various kinds of solid dispersions with different drug/polymer compositions were prepared and their physico-chemical properties were compared. As the polymer content increased, the drug crystallinity in the SDs significantly decreased and the dissolution properties were enhanced. The PVP based SDs were observed to have relatively reduced crystallinity and an enhanced dissolution rate than HPC-based SDs, due to better miscibility between drug and polymer matrix. For PVP based SDs, the drug crystallinity almost disappeared and the dissolution properties significantly increased by more than 3~7 times.