• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.27-31
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• 1975

1. The isolated strips of guinea-pig, fowl and reptiles (snake and tortoise) showed consistenly excitatory responses to $PGE_1\;and\;E_2$, which were dose-dependent. 2. Frog intestine revealed inhibitory responses to both $PGE_1\;and\;PGE_2$ except a small of $PGE_2$ (1-10 ng/ml) caused slight contraction. 3. The intestines of pieces showed inconsistent responses to $PGE_1\;and\;E_2$. In fresh-water fish(carp), $PGE_1$ produced relaxation under the dose of 50 ng/ml, and contraction by the large doses, but $PGE_2$ consistently caused contraction in dose-dependent manner. However, the strips of sea-water fish revealed the different responses to PGE compound: $PGE_1$ caused relaxation and $PGE_2$ conversly contraction even though in small degree. 4. These results that there are genera differences in the responses of the longitudinal strips of intestine to $PGE_1\;and\;PGE_2$ was assumed to be possibly correlated with evolutionally primitive function of gut.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.173-178
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• 2000

The purpose of this work is to develop a transurethral suppository containing prostaglandin $E_1\;(PGE_1)$, which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of $PGE_1.\;PGE_1$ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride $(Suppocire^{\circledR}\;AP,\;SAP)$, polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and $PGE_1$ release of the suppositories were investigated. Ocular irritation test was carried out after application of $PGE_1$ suppository to rabbit's eye. The intracavernous pressure (ICP), penile length and duration of erectile response were determined after transurethral administration of $PGE_1$ suppository and compared with those after intracavernosal injection of $PGE_1$ solution to cats. HCO-50 hardly affected the melting points and viscosities of $PGE_1$ suppositories. Additionally, $PGE_1$ transurethral suppositories, whose melting point ranges was $34-35^{\circ}C$, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of $PGE_1$ from the suppositories. Dissolution mechanism analysis showed the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppositories by Fickian diffusion. The release rate of $PGE_1$ from $PGE_1$ suppository [PGE1/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2 h. This $PGE_1$ suppository gave no significant irritation to the ocular tissue, expecting that it gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, $PGE_1$ in this suppository was stable at $4^{\circ}C$ for 2 years. This suppository increased the ICP and penile erection similar to those of injectable $PGE_1$ solution. However, it gave 2.5-fold increased duration of erectile response than injectable $PGE_1$ solution. Our results suggested that it gave more effective erectile response than injectable $PGE_1$ solution in cats. It is concluded that this $PGE_1$ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of $PGE_1$.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.375-381
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• 2005

A rapid and specific high-performance liquid chromatographic method was developed and validated for the simultaneous determination of prostaglandin $E_{1}\;(PGE_{1})$ and prostaglandin $E_{1}$ ethyl ester $(PGE_{1}-EE)$ in hairless mouse skin homogenate. The sample treatment procedure involved deproteination and precipitation by acetonitrile. $PGE_{1}$ and $PGE_{1}-EE$ in supernatant were separated in a reversed-phase C18 column without being interfered by other components present in hairless mouse skin homogenate. 9-Anthracenecarboxylic acid was used as an internal standard. The retention times of $PGE_{1}$, 9-anthracenecarboxylic acid and $PGE_{1}-EE$ were, 4.5, 9.5 and 18.0 min, respectively. The assay showed linearity from 1 to $40\;{\mu}g/ml$ for both $PGE_{1}$ and $PGE_{1}-EE$. Precision expressed as RSD ranged from 2.3 to 14.1 % for $PGE_{1}$ and 1.6 to 11.0% for $PGE_{1}-EE$. Accuracy ranged from 100.5 to 119.6 % for $PGE_{1}$ and from 98.0 to 103.7% for $PGE_{1}-EE$. This method was employed successfully to follow the time course of concentrations of $PGE_{1}$ and $PGE_{1}-EE$ in hairless mouse skin homogenate for stability study.

• Korean Journal of Materials Research
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• v.8 no.9
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• pp.797-801
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• 1998

The cure kinetics for diglycidyl ether of bisphenol A(DGEBA)/4, 4'-methylene dianiline(MDA) system with or without lOphr of phenyl glycidyl ether(PGE)-acetamide(AcAm) was studied by autocatalytic cure expression. On the dynamic DSC curves, the exothermic peak temperature and the onset temperature of reaction decreased with the addition of PGE-AcAm. Regardless of the addition of PGE-AcAm, the shape of the conversion curve showed sigmoid, and this meant that DGEBA/MDA and DGEBA/MDA/PGE-AcAm systems followed autocatalytic cure reaction. When PGE-AcAm was added to DGEBA/MDA system, the cure rate increased about 1.2~1.4 times due to the catalytic role of hydroxyl groups in PGE-AcAm.

• Korean Journal of Materials Research
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• v.7 no.6
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• pp.460-463
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• 1997

에폭시 수지 계의 경화반응 속도를 증가시키고 기계적 물성을 향상시키기 위해 합성 pheny1 glycidy1 ether(PGE)-acetamide(AcAm)를 diglycidy1 ether of bispenol A(DGEBA)/4,4'-methylene dianiline(MDA)계에 도입하였다. PGE와 AcAm을 2:1의 몰비로 혼합한 후 18$0^{\circ}C$에서 1시간 반응시켜서 PGE-AcAm을 합성하였다. 5phr의 PGE-AcAm이 첨가되었을 때 인장강도가 15% 개선되었으며, 그 이후로는 PGE-AcAm을 합성하였다. 5phr의 PGE-AcAm이 첨가되었을 때 인장강도가 15% 개선되었으며, 그 이후로는 PGE-AcAm의 함량에 관계없이 거의 비슷한 값을 나타내었다. 반면에유리전이 온도(Tg)와 충격강도는 PGE-AcAm의 함량이 증가함에 따라 감소하였다. 파단면은 PGE-AcAm이 첨가됨으로써 더 복잡한 형상을 나타내었다.

• The Korean Journal of Pharmacology
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• v.10 no.1 s.15
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• pp.31-40
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• 1974

1. The authors investigated the effects of $PGE_1$ on the action of sympathomimetics in the vas deferens of guinea-pig, comparing with those in the rat vas deferens, and also the action of $PGE_1$ on the motility of nerve-free smooth muscle of chick amnion. 2. In the isolated guinea-pig vas deferens, the actions of phenylephrine and norepinephrine were much potentiated by pretreatment with $PGE_1$. Futher, in the isolated hypogastric nerve-vas deferens preparation of guinea-pig, effects of phenylephrine, norepinephrine and tyramine on the contractile response of vas to the hypogastric nerve stimulation and to the transmural stimulation were also augumented especially in tension by $PGE_1$-pretreatment. 3. In the isolated hypogastric nerve-vas preparation of rat, both contractile responses to hypogastric nerve and transmural stimulation were slowly reduced by treatment with $PGE_1$ and the potentiated effect of phenylephrine or norepinephrine was not observed in spite of pretreatment with $PGE_1$. 4. The actions of phenylephrine and norepinephrine on the denervated vas deferens of guinea-pig were also enhanced by $PGE_1$ as it were in the intact vas deferens, but there was no significant effect by $PGE_1$ on the action of norepinephrine in the denervated rat vas deferens. 5. $PGE_1$ in low concentration $(10^{-8}g/ml)$ did not affect the spontaneous motility of nerve-free smooth muscle of chick amnion ($9{\sim}11$ th day incubated chick), but in large concentration $(5{\times}10^{-8}g/ml)$ it caused irregular and slightly inhibitory movement. Pretreatment with $PGE_1$ on chick amnion did not exert any change on the action of phenylephrine applied. However, the stimulatory action of physostigmine on the chick amnion was a little antagonized by the low concentration of $PGE_1$. 6. It might be summarized that there is species difference between the actions of $PGE_1$ on the vas deferens of guinea-pig and that of rat, and the action of $PGE_1$ on the guinea-pig vas deferens might be mediated by the other mechanism rather than by direct action on the vas musculature.

• Archives of Reconstructive Microsurgery
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• v.6 no.1
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• pp.1-8
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• 1997

Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilation of the peripheral vessels and platelet disaggreation. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated cutaneous microcirculatory changes in the rabbit ear chamber(REC) with an intravital microscope following intravenous administration of $PGE_1$. The results obtained in this study indicate that $PGE_1$ administered intravenously at a rate of 200ng/kg/min might act directly on the vessels and cause dilatation of metarterioles and capillaries without affecting vasomotion and systemic blood pressure. Clinically in order to evaluate the effect of an intravenous administration of $PGE_1$ on the cutaneous microcirculation, cutaneous blood flow, skin temperature and transcutaneous $Po_2$ in the pedicle or free flap of operated patients were evaluated by the combination of several measurements following the administration of $PGE_1$. The present study suggests that improvement of cutaneous microcirculation by $PGE_1$ may enhance the survival rate of flap or replantation. Both vessel arterial ischemia and venous congestion are main factors of tissue necrosis in the flap surgery. Vasodilatory or antithrombotic agents have been used in salvage of flap necrosis. However, the therapeutic effects of those drugs are still not well elucidated. Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilatation of the peripheral vessels and platelet disaggregation[1-3]. Emerson and sykes[4] have obtained significant improvement in the flap survival in the rat using $PGI_2$. Suzuki et al.[5] have reported prolonged flap survival length by using $PGE_1$ in the rabbit and concluded that $PGE_1$ improved the microcircuration in the flap. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated microcirculatory changes in the rabbit ear chamber[6,7] with an intravital microscope following intravenous administration of $PGE_1$.

• Journal of Biomedical Engineering Research
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• v.28 no.4
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• pp.484-493
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• 2007

Two polymeric prodrugs of PGE1 (prodrugs IVg and PNg) were newly synthesized. The drug conjugation proceeded in quantitative yield without decomposition of PGE1 to PGA1. With two types conjugates, PEG-PGE1 and PN-PGE1 with different spacer groups, we first discovered a possibility of slow release of PGE1 in blood circulatory system. PGE1 is conjugated with PEG and PN through the long alkylene spacers, and their availability as polymeric prodrugs is evaluated. Their drug-releasing behavior was examined both in phosphate buffer (pH=7.4) and rat plasma. Each prodrug was known to be highly stabile in the buffer solution. The drug-releasing rate became much faster in rat plasma than in the buffer solution due to the acceleration by the plasma enzymes. The drug-release was found to reach a plateau in rat plasma because the released PGE1 or its derivatives may be captured or decomposed by the plasma proteins. The slower drug-releasing rate of pro drug PNg in rat plasma is reasonably attributed to the molecular aggregation due to the hydrophobic bonding between the PGE1 moieties and spacers.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.223-229
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• 2006

[ $PGE_1$ ]-ethyl ester intraurethral solutions were prepared in ethanol/propylene glycol mixture with penetration enhancer and viscosity-enhancing agent. The stability of $PGE_1$-ethyl ester in intraurethral solution was investigated at various temperature. Simultaneous determination of $PGE_1$-ethyl ester and $PGE_1$ was performed using a validated HPLC technique. In pentobarbital anesthetized cats, increase in intracavernous pressure(ICP), increase in penile length and duration of erectile response were determined after intraurethral application of $PGE_1$-ethyl ester solutions. $PGE_1$-ethyl ester solutions, when instilled into the eyes of rabbits, produces no noticeable irritation, or slight transient conjunctival irritation. From these results, ocular irritation of this solutions was judged as practically non-irritating. The stability study indicates that the therapeutically effective content in solution is well maintained for 46 weeks or longer when they are stored at $4^{\circ}C$. After intraurethral application of $PGE_1$-ethyl ester, ICP was increased and penile erection was induced. $PGE_1$-ethyl ester intraurethral solutions for erectile dysfunction could be developed and evaluated by employing feline erection model.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.260-267
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• 2005

[ $PGE_1$ ] is an endogenous substance of potent vasodialator as well as inhibitor of platelet aggregation. It has been used therapeutically in peripheral arterial occlusive disease and impotence. Intracavernous injection of $PGE_1$ for erectile dysfunction has been established for several years as a treatment option for erectile dysfunction of diverse etiologies, but this mode of administration is limited by penile discomfort, pain at the injection site, inconvenience and noncompliance. As the matter of worse, the $\beta-hydroxy$ moiety of $PGE_1$ is extremely susceptible to dehydration in solution to give inactive $PGA_1$ and $PGB_1$. For the improvement of stability, rapid absorption at action site and the convenience of application, $PGE_1$ was formulated as urethral suppositories of three types of formulations, such as PEG, witepsol, and the mixture of PEG and witepsol. The stability test of $PGE_1$ and the release test in urinary suppositories were performed. Futhermore, the effect of enhancers and vehicle composition on the penetration of $PGE_1$ through excised rat skin was evaluated by permeability coefficient and enhancement ratio.