• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1997.04a
• /
• pp.115-115
• /
• 1997

A new capsaicin analog modified with 4-hydroxyl and alkyl chain of capsaicin was a very potent antiinflammatory analgesic drug and may be clinically useful for those who have rheumatoid arthritis, diabetic neuropathy and cancer. The purpose of this study was to investigate histopathology after short and long term application of poloxamer-based gels, and percutaneous absorption of various topical formulations. Poloxamer-based gel was prepared by cold method using poloxamer 407. The poloxamer gels was applied to dorsal sites of hairless mouse skin during one week or one month for the evaluation of skin irritation. The applied site was then sectioned for histopathologic examination. The topical formulations were also prepared using CMC, HPMC, MC, carbopol and glycerylmono stearate. Skin variation of poloxamer gels was studied using excised hairless mouse, rat, hamster and human penis skin. Franz-type diffusion cells were used far skin penetration of drug against receptor phase filled with about 10$m\ell$ of 0.9% saline solution kept at 32$^{\circ}C$. The concentration of drug was determined by the reverse phased C18, Symmetry HPLC with fluorometeric detector. No skin erythema was observed after dorsal application of poloxamer-based gels for one week or one month. No histopathologic changes was also examined, suggesting no skin toxicity of poloxamer-based gels. The order of flux rate was HPMC > MC ( CMC > poloxamer >> glycerylmono stearate ( carbopol. There was a skin variation of poloxamer gels. The flux rate of poloxamer gels was highest in case of hairless mouse followed by rat, human and hamster skin. The Partial support-Ministry of Science and Engineering (HAN project).

• The Journal of Korean Medicine
• /
• v.33 no.2
• /
• pp.11-24
• /
• 2012

Objectives: This study was designed to evaluate lipid-lowering and antioxidant effects of Artemisia capillaris(A. capillaris) using a model of hyperlipidemic rats induced by poloxamer-407. Methods: Rats were previously treated by A. capillaris water extract, and intraperitoneally injected by poloxamer-407 to induce hyperlipidemia. Parameters of serum lipid and oxidative stress biomarkers were determined. Results: 1. A. capillaris ameliorated the elevation of serum total cholesterol, triglyceride, LDL-cholesterol and MDA level. 2. A. capillaris ameliorated the reduction of serum TAC and SOD activities. 3. A. capillaris ameliorated the reduction of serum GSH and GSH-reductase level. Conclusions: According to these results, A. capillaris can be used to treat hyperlipidemia or as basis for making new drugs for treating hyperlipidemia in the future.

• Korean Journal of Pharmacognosy
• /
• v.43 no.2
• /
• pp.101-106
• /
• 2012

The anti-hyperlipidemic effect of Houttuynia cordata was assessed in poloxamer-407 induced hyperlipidemic mice model. The butanol fraction and its isolated compound, quercetin-3-O-rhamnoside, significantly reduced the blood triglyceride and total-cholesterol level and increased the blood HDL-cholesterol level. They also showed the significant reductive effect on the blood AST and ALT level, rising in proportion to the liver damage, in hyperlipidemic mice.

• Journal of Pharmaceutical Investigation
• /
• v.28 no.3
• /
• pp.177-183
• /
• 1998

Low toxicity, reverse thermal gelation and high drug loading capabilities suggest that poloxamer 407 gels have great potential as a topical drug delivery system. Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of skin irritancy due to its acidic pH. Poloxamer gels of different polymer contents were formulated to overcome the problem and compared to the cream type formulations of either w/o/w multiple emulsion cream or o/w type emulsion cream. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solutions. Drug release from w/o/w multiple emulsion cream was controlled by oil membrane, showing the apparent zero order release kinetics. The KA release from the poloxamer gels was also controlled by the gel matrix, showing that drug release increased linearly as KA contents increase, but decreased exponentially as the polymer contents increase. In the skin irritancy test, the primary irritancy index(PII) of poloxamer gel base was lower than those of multiple emulsion cream base and o/w cream. Depending on KA contents or polymer contents in the gel. PH values in poloxamer gels were ranged from 1.3 to 2.0, which are interpreted as low or negligible irritation on skin. There was a good correlation between the log value of flux in drug release and PII value in skin irritation. It was possible to conclude that the poloxamer gels containing KA might be a good candidate for an antimelanogenic topical delivery system by virtue of the controlled release of the drug and the reduced skin irritancy.

• Herbal Formula Science
• /
• v.21 no.1
• /
• pp.99-110
• /
• 2013

Objectives : This study was designed to investigate the effect of a herbal preparation HJ01 consisting of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus and Glycyrrhizae Radix on adipocyte differentiation in OP9 cells and on poloxamer 407(P-407)-induced hyperlipidemia in mice. Methods : 1. MTT assay was used to evaluate the potential cytotoxicity of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01, respectively. 2. Bone-marrow derived OP9 cells were treated with HJ01, and the alterations in fat storage in the cells were determined by the Oil red O assay. 3. The protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$), as a adipocyte differentiation marker, was examined using western blot analysis in differentiated OP6 cells. 4. Adult male C57BL6 mice received intraperitoneal injections of P407 to induce hyperlipidemia, simultaneously, were treated with HJ01 for 4 weeks. Then the cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-c) levels in sera and liver tissues were measured. Results : 1. The MTT assay exhibited that Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01 showed no significant cytotoxicity in tested dosages. 2. Ten days' treatment with HJ01 markedly inhibited the increases in fat storage in differentiated OP6 cells. 3. Four weeks' treatment with HJ01 down-regulated the protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$) but up-regulated the levels of adiponectin in differentiated OP9 cells. 5. HJ01 inhibited the accumulation of TC and TG in liver tissues and increased serum levels of TC in hyperlipidemic mice. Conclusions : These results suggest that HJ01 can in vitro inhibit adipocyte differentiation and fat storage in OP6 cells, in vivo improve the hyperlipidemia induced by P-407 in mice, which may be mediated by promoting glucose uptake and improving a lipid metabolite profile.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.2
• /
• pp.109-114
• /
• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.

• YAKHAK HOEJI
• /
• v.50 no.1
• /
• pp.1-7
• /
• 2006

The purpose of the present study was to formulate the aqueous solution of 1-cyclopent-3-enylmethyl-6(3,5-dimethyl-benzoyl)-5-ethyl-1H-pyrimidine-2,4-dione (CPD), a novel antivirus compound containing pirimidine structure. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants (Tween 80, Cremophor$^{(R)}$ RH40, Cremophor$^{(R)}$ EL, Poloxamer 407, Poloxamer 188) and a complexation agent [hydroxypropyl-${\beta}$-cyclodextrin (HPBCD)] , on the solubility of CPD in aqueous solution were evaluated. The solubility of CPD in water was under $1\;{\mu}g/ml$ at $20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of CPD at the $0{\sim}40\%$ concentration range. The solubility of CPD was significantly elevated by the addition of cosolvents over the $80\%$ concentration range. On the other hand, tween 80, Cremophor$^{(R)}$ L, Cremophor$^{(R)}$ RH40, and HPBCD showed enhanced effects on the solubility of CPD. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the CPD solubility were less pronounced compared with tween 80, Cremophor$^{(R)}$ L or Cremophor$^{(R)}$ RH40. As a results, tween 80 aqueous solution was selected as an optimum solvent system. The aqueous solutions containing $20\%$ tween 80 were formulated as a dosing solution containing CPD for its intraperitoneal and intrahypodermic administration, respectively, The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
• /
• v.34 no.5
• /
• pp.385-391
• /
• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 in water was under $1\;{\mu}g/ml\;at\;20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
• /
• v.35 no.3
• /
• pp.165-171
• /
• 2005

Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. However, it is difficult for itraconazloe to be delivered by topical system due to its poor aqueous solubility. First, niosomes containing drug were prepared with span 60, cholesterol. tocopherol and poloxamer 407 as vesicle forming agents in an effort to increase solubility of itraconazole. And then prepared niosomes were dispersed in O/W creams (containing xanthan gum, glycerin, vaseline, glyceryl monostearate and $Cerix^{\circledR}-5$) or gels (containing xanthan gum and poloxamer 407). Both creams and gels were evaluated with respect to their rheological properties, in vitro permeation through excised skin of hairless mouse. Creams or gels containing niosome showed pseudoplastic flow and hysteresis loop. For both creams and gels, viscosity was increased with increasing the content of glycerine or vaseline and the content of gel forming polymer, respectively. In creams, the permeability of drug to skin was decreased with increasing the viscosity of cream. The permeability of drug was affected by pH as well as viscosity of gel. In vitro permeation test results demonstrated that cream formulations showed better permeability than gels. In conclusion, these results suggest that creams formulation containing niosome can be useful for the topical delivery of intraconazole.

• KSBB Journal
• /
• v.31 no.4
• /
• pp.219-227
• /
• 2016

Valsartan, a drug for the treatment of cardiovascular disease, exhibited low bioavailability which was caused by, at least in part, limited solubility at low pH. Present investigation deals with the preparation and characterization of gastro-retentive drug delivery system (GRDDS) using valsartan solid dispersion. We prepared solid dispersion using surfactants (Poloxamer 407) and alkalizer ($Na_2CO_3$) which may to be useful for improving solubility of valsartan at low pH and evaluated by saturated solubility of valsartan in distilled water. Valsartan gastro-retentive (GR) tablets containing solid dispersion prepared and evaluated by weight variation, floating time and dissolution rate. Compression at lower pressures resulted in the tablets floating over simulated gastric fluid (pH 1.2) for more than 17 h. In vitro release of valsartan from GR tablet was dependent on the amount of poloxamer 407 and hydroxypropyl methylcellulose. On the basis of evaluation parameter, formulation E-3 was selected as a final formulation. Therefore, it can be concluded that the GR tablets containing solid dispersion may be exploited successfully for the delivery of poorly drug such as valsartan.