Preparation and in Vitro Release of Melatonin-Loaded Multivalent Cationic Alginate Beads

Lee, Beom-Jin,Min, Geun-Hong,Kim, Tae-Wan The Pharmaceutical Society of Korea 1996 Archives of Pharmacal Research Vol.19 No.4

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$. The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$</TEx> induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++}<Zn^{++}<Ca^{++}.iden.Ba^{++}. \;In\; case\; of\; Al^{+++}$ the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.

Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice -Effect of Agarwood on Histamine Release and Scratching Behavior-

Inoue, Eiji,Shimizu, Yasuharu,Masui, Ryo,Tsubonoya, Tomoe,Hayakawa, Tomomi,Sudoh, Keiichi KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.3

Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

In Vitro/in Vivo Relationship of Gabapentin from a Sustained-Release Tablet Formulation: A Pharmacokinetic Study in The Beagle Dog

Rhee, Yun-Seok,Park, Seok,Lee, Tae-Won,Park, Chun-Woong,Nam, Tae-Young,Oh, Tack-Oon,Jeon, Ji-Woong,Han, Sang-Beom,Lee, Dong-Soo,Park, Eun-Seok 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

The aim of this study was to examine the in vitro/in vivo relationship of the drug release behavior of a sustained-release formulation of gabapentin. The immediate-release formulation was used as the reference formulation. The dissolution test was employed using pH 1.2, 4.0, or 6.8 buffer solution, or water, to determine the in vitro release behaviors of gabapentin tablets. Gabapentin was released completely within 1 h from the immediate-release tablet and released for 12 h from the sustained-release tablet. A single dose (600 mg) of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. Although the sustained-release tablet did not disintegrate and had slow drug release characteristics, it showed similar pharmacokinetic parameters to the immediate-release tablet, which rapidly disintegrated and showed fast drug release. Thus, the in vivo release of gabapentin did not correlate with in vitro release of drug.

[$Ca^{2+}-induced$ $Ca^{2+}$ Release from Sarcoplasmic Reticulum Negatively Regulates Myocytic ANP Release in Beating Rabbit Atria

Li, Dan,Quan, He Xiu,Wen, Jin-Fu,Jin, Jing-Yu,Park, Sung-Hun,Kim, Sun-Young,Kim, Sung-Zoo,Cho, Kyung-Woo The Korean Society of Pharmacology 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.2

It is not clear whether $Ca^{2+}-induced$ $Ca^{2+}$ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that $Ca^{2+}$ entry via voltage-gated L-type $Ca^{2+}$ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR $Ca^{2+}$ release in the regulation of ANP release and whether $Ca^{2+}$ entry via L-type $Ca^{2+}$ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR $Ca^{2+}$ release, increased atrial myocytic ANP release ($8.69{\pm}3.05$, $19.55{\pm}1.09$, $27.31{\pm}3.51$, and $18.91{\pm}4.76$% for 1, 2, 3, and $6{\mu}M$ ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR $Ca^{2+}$ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type $Ca^{2+}$ channel with nifedipine abolished ryanodine-induced increase in ANP release ($0.69{\pm}5.58$% vs. $27.31{\pm}3.51$%; P<0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that $Ca^{2+}$-induced $Ca^{2+}$ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

In Vitro/in Vivo Relationship of Gabapentin from a Sustained- Release Tablet Formulation: A Pharmacokinetic Study in The Beagle Dog

이윤석,박천웅,남태영,오택운,전지웅,한상범,박은석,박세옥,이태원,이동수 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

The aim of this study was to examine the in vitro/in vivo relationship of the drug release behavior of a sustained-release formulation of gabapentin. The immediate-release formulation was used as the reference formulation. The dissolution test was employed using pH 1.2, 4.0, or 6.8 buffer solution, or water, to determine the in vitro release behaviors of gabapentin tablets. Gabapentin was released completely within 1 h from the immediate-release tablet and released for 12 h from the sustained-release tablet. A single dose (600 mg) of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. Although the sustained-release tablet did not disintegrate and had slow drug release characteristics, it showed similar pharmacokinetic parameters to the immediate-release tablet, which rapidly disintegrated and showed fast drug release. Thus, the in vivo release of gabapentin did not correlate with in vitro release of drug.

Is Pancapsular Release More Effective than Selective Capsular Release for the Treatment of Adhesive Capsulitis?

Nam Hoon Moon,Seung-Jun Lee,Won Chul Shin,Sang Min Lee,Kuen Tak Suh 대한견주관절의학회 2015 대한견주관절학회지 Vol.18 No.1

Background: We assessed the effectiveness of arthroscopic capsular release for the treatment of adhesive capsulitis. Further, we tried to ascertain the clinical benefits, if any, of pancapsular release over selective capsular release, where the two differ by performing or not performing a posterior capsular release, respectively. Methods: Thirty-five consecutive patients with either primary or secondary adhesive capsulitis who failed conservative treatment for more than 6 months were enrolled in the study. A total of 16 patients allocated in group 1 received a pancapsular release that comprises the release of the rotator interval, anteroinferior capsular, and the posterior capsular release, whereas 19 patients in group 2 received a selective capsular release that comprises only the release of the rotator interval release and anteroinferior capsular release. The clinical outcomes, visual analogue scale (VAS) score, Constant score, and range of motion, were assessed preoperative and postoperatively. Results: In both groups, the preoperative VAS score, Constant score, and ROM showed a significant improvement by the 6-month follow-up. We found that the immediate postoperative internal rotation was significantly higher in group 1 than group 2. Despite significant differences seen between the two groups at the initial postoperative period, there were no significant differences in Constant score, VAS score, and the ROM at all the subsequent follow-ups between the two groups. Conclusions: Arthroscopic capsular release for the treatment of adhesive capsulitis is very effective. However, pancapsular release did not show any advantage over selective capsular release in terms of overall clinical outcome.

Ca<SUP>2⁢</SUP>-induced Ca<SUP>2⁢</SUP> Release from Sarcoplasmic Reticulum Negatively Regulates Myocytic ANP Release in Beating Rabbit Atria

Dan Li,He Xiu Quan,Jin Fu Wen,Jing Yu Jin,Sung Hun Park,Sun Young Kim,Sung Zoo Kim,Kyung Woo Cho 대한생리학회-대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.2

It is not clear whether Ca<SUP>2⁢</SUP>-induced Ca<SUP>2⁢</SUP> release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that Ca<SUP>2⁢</SUP> entry via voltage-gated L-type Ca<SUP>2⁢</SUP> channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR Ca<SUP>2⁢</SUP> release in the regulation of ANP release and whether Ca<SUP>2⁢</SUP> entry via L-type Ca<SUP>2⁢</SUP> channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR Ca<SUP>2⁢</SUP> release, increased atrial myocytic ANP release (8.69⁑3.05, 19.55⁑1.09, 27.31⁑3.51, and 18.91⁑4.76% for 1, 2, 3, and 6μM ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR Ca<SUP>2⁢</SUP> pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type Ca<SUP>2⁢</SUP> channel with nifedipine abolished ryanodine-induced increase in ANP release (0.69⁑5.58% vs. 27.31⁑3.51%; P<0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that Ca<SUP>2⁢</SUP>-induced Ca<SUP>2⁢</SUP> release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

Effects of NMDA, AMPA and Kainate on the Release of Acetylcholine in Rat Hippocampal and Striatal Slices

Kim, Do Kyung,Lee, Se-Oul,Jung, Kyu-Yong,Kim, Jong-Keun,Choi, Bong-Kyu The Korean Society of Pharmacology 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.6

This study examined the effects of N-methyl-D-aspartate (NMDA), ${\alpha}-amino$-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate on basal and electrically-evoked release of acetylcholine (ACh) from the rat hippocampal and striatal slices which were preincubated with $[^3H]choline$. Unexpectedly, the basal and evoked ACh release were not affected at all by the treatment with NMDA $(3{\sim}100{\mu}M)$, AMPA $(1{\sim}100{\mu}M)$ or kainate $(1{\sim}100{\mu}M)$ in hippocampal slices. However, in striatal slices, under the $Mg^{2+}-free$ medium, $30{\mu}M$ NMDA increased the basal ACh release with significant decrease of the electrically-evoked releases. The treatment with $1{\mu}M MK-801 not only reversed the $30{\mu}M$ NMDA-induced decrease of the evoked ACh release, but also attenuated the facilitatory effect of $30\;{\mu}M$ NMDA on the basal ACh release. The treatment with either $30\;{\mu}M$ AMPA or $100\;{\mu}M$ kainate increased the basal ACh release without any effects on the evoked release. The treatment with $10{\mu}M$ NBQX abolished the AMPA- or kainate-induced increase of the basal ACh release. Interestingly, NBQX significantly attenuated the evoked release when it was treated with AMPA, although it did not affect the evoked release alone without AMPA. These observations demonstrate that in hippocampal slices, ionotropic glutamate receptors do not modulate the ACh release in cholinergic terminals, whereas in striatal slices, activations of ionotropic glutamate receptors increase the basal ACh release though NMDA may decrease the electrically-evoked ACh release.

마찰저항이 연속누출과 순간누출을 가지는 액체 풀의 확산에미치는 영향에 대한 해석적 연구

김태훈,최병일,김명배,도규형,한용식 한국수소및신에너지학회 2013 한국수소 및 신에너지학회논문집 Vol.24 No.6

In this study, solutions for a liquid pool spreading model with continuous and instantaneous release are discussed based on the model used in the FERC's report. The effects of the release time on the liquid pool volume and radius are investigated for the continuous release. For the continuous release with the frictional resistance force in the liquid pool spreading model, the vaporization time decreases as the release time increases. On the other hand, for the continuous release without the frictional resistance force in the liquid pool spreading model, the vaporization time increases as the release time increases. These phenomena are deeply related to the pool radius. In addition, the effects of the initial pool radius for the instantaneous release in the liquid pool spreading model are discussed. For the case with the frictional resistance force in the liquid pool spreading model, as reducing release time in the model with the frictional resistance force for the continuous release, the solution for a continuous release approaches to that for an instantaneous release. On the contrary to this, the pool volume and radius for the instantaneous release without the frictional resistance force are totally different from those for the continuous release without the frictional resistance force.

인간 대뇌피질에서 고칼륨에 의한 [^3H] Norepinephrine 유리의 특성

양동호,조규박,김형근 의과학연구소 1998 全北醫大論文集 Vol.22 No.2

It has been reported that norepinephrine(NE) and Υ-aminobutyric acid(GABA) play important roles in epileptic seizure. IN human central nervous system, however, characteristics of NE release and the influe-nce of GABA have not been elucidated yet. In this study, the mechanism of autoregulation [^3H]NE release evoked by high-potassium and the influence of GABAergic drugs were investigated in epileptic human ce-rebral cortex slices. Potassium stimulated [^3H]NE release in a dose-dependent manner. High potassium(15mM)-evoked release of [^3H]NE was abolished by removal of calcium from incubation media. Tetrodotoxin(TTX), also, profoundly inhibited [^3H]NE release. Clonidine and oxymetazoline, agonists for α_2-adrenocep-tor, inhibited the potassium-evoked release of [^3H]NE in a dose-dependent manner, respectively. Yohim-bine, an antagonist for α_2-adrenoceptor, potentiated [^3H]NE release in a dose-dependent manner. The inhi-bitory effect of clonidine on [^3H]NE release was antagonized by 0.1 μM of yohimibine. however, phenyle-phrine and methoxamine, agonists for α_1-adrenoceptor, did not inhibit the potassium-stmulaed release of [^3H]NE Desipramine, a NE transporter blocker, potentiated [^3H]NE release in a dose-dependent manner. Baclofen, a GABA_B agonist, inhibited the potassium-stimulated [^3H]NE release. The inhibitory effect of bac-lofen was antagonized by 5-aminovaleric acid(5-AV), a GABA_B antagonist. Neither, muscimol, a GABA_A ago-nist, nor bicuculline, a GABA_A antagonist, influenced on the potassium-stimulaed [^3H]NE release. These results suggest that high potassium-stimulated release of NE is autoregulated by α_2-adrenoceptor, and released NE is removed by Ne transporter from synaptic cleft, that the potassium-stimulated release of NE can be regulated by GABA receptors, not GABA_A but GABA_B, in human cerebral cortex. (KEy words : Human Cerebral cortex, norepinephrine release, opioid receptor)