• Title/Summary/Keyword: Administration and dosage

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Development of Luteinizing Hormone Releasing Hormone (LHRH) Delivery Systems for Vaginal Mucosal Route

  • Han, Kun;Park, Jeong-Sook;Youn, Bok-Chung;Nam, Joo-Jeong;Park, Hee-Beom;Joseph-R. Robinson
    • Archives of Pharmacal Research
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    • v.18 no.5
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    • pp.325-331
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    • 1995
  • The objective of this study was to find a rational dosage form for vaginal mucosal delivery of LHRH. Vaginal absorption of LHRH was estimated by measuring its ovulation inducting effect in rat and in vitro vaginal membrane permeation study in rabbit. THe effects of different hydrogel bases, such as Polycarbophil and Pemulen compared with solutions on vaginal membrane permeation of LHRH were investigated. Sodium laurate, disodium ethylenediamine brane permeaiton of LHRH were investigated. Sodium ethylenediamine tetraacetate (EDTA) and sodium tauro-24, 25-dihydrofusidate (STDHF), which are effective peptidase inhibitors were chosen as additives to a LHRH hydrogel delivery system and LHRH solutions. A Polycarbophil compared with a solution formulation 3.4 times increase in LHRH vaginal membrane permeability compared with a solution formulation. Vaginal membrane permeability from the Polycarbophil was greater than that from Pemulen hydrogels. This may be due to the larger bioadhesive values. LHRH solution with EDTA(2%), STDHF(1%) and sodlaurate(0.5%) showed 4.1 times, 4.8 times and 6.0 times of ovulation inducing activity compared with control. These results suggest that enzyme inhibition effect of EDTA, STDHF and sod, laurate may be result in substantial enhancement of vaginal absorption. By administraiton of Polycarbophil hydrogels containing LHRH the ovulation inducing activity was 3.3 times greater than the solutions. This result indicates the bioadhesive hydrogels as well as peptidase in hibition significantly improved absorption of LHRH. By coadministration with these inhibitors the ovulation inducing activity of Polycarbophi hydrogel containing LHRH was comparable with subcutaneous administration in ovulation inducing activity.

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Preliminary study on the effects of pergolide on left ventricular function in the horses with pituitary pars intermedia dysfunction

  • Gehlen, Heidrun;Fisch, Judith;Merle, Roswitha;Trachsel, Dagmar S.
    • Journal of Veterinary Science
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    • v.22 no.5
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    • pp.64.1-64.12
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    • 2021
  • Background: Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. Objectives: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. Methods: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group. Results: Twenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups. Conclusions: No changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.

An In sight into Novel Drug Delivery System: In Situ Gels

  • Bashir, Rabiah;Maqbool, Mudasir;Ara, Irfat;Zehravi, Mehrukh
    • CELLMED
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    • v.11 no.1
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    • pp.6.1-6.7
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    • 2021
  • In situ gelling devices, as they enter the body, are dosage forms in the shape of the sol but turn into gel types under physiological circumstances. Transition from sol to gel is contingent on one or a mixture of diverse stimuli, such as transition of pH control of temperature, irradiation by UV, by the occurrence of certain ions or molecules. Such characteristic features may be commonly employed in drug delivery systems for the production of bioactive molecules for continuous delivery vehicles. The technique of in situ gelling has been shown to be impactful in enhancing the potency of local or systemic drugs supplied by non-parenteral pathways, increasing their period of residence at the absorption site. Formulation efficacy is further improved with the use of mucoadhesive agents or the use of polymers with both in situ gelling properties and the ability to bind with the mucosa/mucus. The most popular and common approach in recent years has provided by the use of polymers with different in situ gelation mechanisms for synergistic action between polymers in the same formulation. In situ gelling medicine systems in recent decades have received considerable interest. Until administration, it is in a sol-zone and is able to form gels in response to various endogenous factors, for e.g elevated temperature, pH changes and ions. Such systems can be used in various ways for local or systemic supply of drugs and successfully also as vehicles for drug-induced nano- and micro-particles. In this review we will discuss about various aspects about use of these in situ gels as novel drug delivery systems.

Adsorption Characteristics of Ammonia-Nitrogen by Zeolitic Materials Synthesized from Jeju Scoria (제주 스코리아로부터 합성한 제올라이트 물질에 의한 암모니아성 질소의 흡착 특성)

  • Lee, Chang-Han;Hyun, Sung-Su;Kam, Sang-Kyu
    • Journal of Environmental Science International
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    • v.29 no.12
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    • pp.1261-1274
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    • 2020
  • The characteristics of ammonia-nitrogen (NH4+-N) adsorption by a zeolitic material synthesized from Jeju scoria using the fusion and hydrothermal method was studied. The synthetic zeolitic material (Z-SA) was identified as a Na-A zeolite by X-ray diffraction, X-ray fluorescence analysis and scanning electron microscopy images. The adsorption of NH4+-N using Jeju scoria and different types of zeolite such as the Z-SA, natural zeolite, and commercial pure zeolite (Na-A zeolite, Z-CS) was compared. The equilibrium of NH4+-N adsorption was reached within 30 min for Z-SA and Z-CS, and after 60 min for Jeju scoria and natural zeolite. The adsorption capacity of NH4+-N increased with approaching to neutral when pH was in the range of 3-7, but decreased above 7. The removal efficiency of NH4+-N increased with increasing Z-SA dosage, however, its adsorption capacity decreased. For initial NH4+-N concentrations of 10-200 mg/L at pH 7, the adsorption rate of NH4+-N was well described by the pseudo second-order kinetic model than the pseudo first-order kinetic model. The adsorption isotherm was well fitted by the Langmuir model. The maximum uptake of NH4+-N obtained from the Langmuir model decreased in the order of Z-CS (46.8 mg/g) > Z-SA (31.3 mg/g) > natural zeolite (5.6 mg/g) > Jeju scoria (0.2 mg/g).

The Effect of KyungOcGogamibang on the Growth of the Rats (경옥고가미방(瓊玉膏加味方)이 흰쥐의 성장(成長)에 미치는 영향(影響))

  • Jung, Bong-Kyun;Yun, Hye-Jin;Lee, Yu-Jin;Kang, Mi-Sun;Baek, Jung-Han
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.1
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    • pp.141-158
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    • 2009
  • Objectives The purpose of this study is to find out the effect of KyungOcGogamibang(KOGE) on the growth of rats. Methods First of all, we divided male Sprague-Dawley rats into 4 groups(KOGE1, KOGE2, KOGE3 and control group). Then KOGE1, KOGE2 and KOGE3 groups were administered with KOGE water extracts once a day at a dosage of 250, 500, 1,000mg/kg respectively for 3 weeks. The control group was administered with normal saline in the same manner. We measured the rat's body weight, amount of body weight increased, length of femur, serum GH, serum IGF-Ⅰ, serum TSH and serum testosterone after each week of administration. Results 1. There were significant changes of the rat's body weight, the length of the femur, the level of GH, IGF-Ⅰand TSH in KOGE1 groups. 2. There were significant changes of the rat's body weight, the length of the femur, the level of IGF-Ⅰand TSH in KOGE2 groups. 3. There were significant changes of the rat's body weight, the length of the femur, the level of IGF-Ⅰand TSH in KOGE3 groups. Conclusions According to the results above, rat in KOGE group have been increased their body weight, length of femur, serum GH, serum IGF-1 compared to the control group. This study shows that groups of KOGE have an effect on promoting the growth, thus it is expected to treat growth problems for children.

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The Effect of Recombinant Tissue Plasminogen Activator on the Intracerebral Hematomas in Experimental Cat Models

  • Jo, Kwang-Wook;Kim, Seong-Rim;You, Seung-Hoon;Kim, Sang-Don;Park, Ik-Seong;Baik, Min-Woo
    • Journal of Korean Neurosurgical Society
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    • v.37 no.4
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    • pp.287-292
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    • 2005
  • Objective: Recent clinical studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator(rt-PA) can facilitate the normal clearing of blood from the subarachnoid space. Urokinase, a first generation fibrinolytic agent, has been used to liquify such clots with some success. Therefore, recombinant tissue plasminogen activator, a second generation fibrinolytic drug that may be safer and more effective, is studied to evaluate its dosage to lyse clots in vitro and reactivity in the brain parenchyme. Methods: Intracerebral hematomas were created by stereotactically injecting 2ml of clotted autogenous blood into the brain parenchyme of total 28 anesthetized adult cats (weighting 3.8 to 4.1 kg). The control animals (group A) received 1 ml of normal saline injected into the clots and the experimental animals received each 0.1 mg of rt-PA (group B), 0.5mg of rt-PA (group C) and 1 mg of rt-PA (group D) at 6 hours after the clot injection. Results: 1. The amount of remained clots after lysing the hematomas were as follows: $1.80{\pm}0.17ml$ in group A, $1.65{\pm}0.23ml$ in group B, $0.61{\pm}0.37ml$ in group C and $0.52{\pm}0.34$ in group D. The result indicated that hematomas in rt-PA treated groups (C & D) were lysed better than the control group. 2. At least 0.5mg of rt-PA should be required for the lysis of 2ml of hematomas. 3. Light microscopic examination revealed no histological evidence of hemorrhage in tissue sections from each brain. Conclusion: Recombinant tissue plasminogen activator may be safely and effectively employed for the lysis of intracerebral hematomas in animal model.

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABAA Receptor Cl- Channel Activation

  • Ma, Yuan;Ma, Hong;Jo, Young-Jun;Kim, Dong-Seon;Woo, Sung-Sick;Li, Rihua;Hong, Jin-Tae;Moon, Dong-Cheul;Oh, Ki-Wan;Eun, Jae-Soon
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.328-335
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    • 2008
  • This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through $\gamma$-aminobutyric acid (GABA) receptor $Cl^-$ channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and $Cl^-$ sensitive fluorescence probe were used to detect the expression of $GABA_A$ receptor subunits and $Cl^-$ influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 ${\mu}M$) increased $Cl^-$ influx in primary cultured cerebellar granule cells, and selectively increased the $GABA_A$ receptor $\alpha$-subunit expression, but had no effect on the abundance of $\beta$ or $\gamma$-subunits. Chronic treatment with 20 ${\mu}M$ honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through $GABA_A$ receptor $Cl^-$ channel activation.

The Effect of Hwangryunhaedoktang on the Toxicity of Dried Mylabris phalerata Extract (황련해독탕(黃蓮解毒湯)이 반묘(斑猫)의 독성에 미치는 영향)

  • Kim, Seong-Mo;Choi, Hong-Sik;Seo, Bu-Il
    • The Korea Journal of Herbology
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    • v.25 no.2
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    • pp.41-54
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    • 2010
  • Objectives : This study was carried out to investigate the anti-toxicity effect of Hwangryunhaedoktang on the dried Mylabris phalerata extract containing cantharidin in ICR mouse. Methods : Dried Mylabris phalerata extracts were orally administered at dosage level 2000, 1000, 500, 250 and 125mg/kg, respectively with and/or without administration of Hwangryunhaedoktang 200mg/kg. During 2 weeks, the changes of body weight, mortality, $LD_{50}$, macroscopic changes of gastrointestinal tract and liver, changes of serum gastrin and somatostatin levels were observed. Results : Decrease of body weight gains was observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Increase of mortality rates was observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. The $LD_{50}$ of dried Mylabris phalerata extract in male mice significantly increased in a case of concomitant used of Hwangryunhaedoktang 268.86 vs 662.05mg/kg. Clinical signs were observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging after dosaging. Increase of number of hemorrhagic and/or erythematous spots in the gastrointestinal tracts, enlargement and congestion in the liver were observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Increase of serum gastrin level was observed in dried Mylarbis phalerata extract-dosing groups, these state of abnormal increase was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Decrease of serum somatostatin level was observed in dried Mylabris phalerata extract-dosing groups, these state of abnormal decrease was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Conclusions : We could conclude that the Hwangryunhaedoktang has anti-toxicity effect on the dried Mylabris phalerata extract containing cantharidin.

Multiple Shoot Induction from Ex Vitro and In Vitro Derived Stein Node Culture of Populus alba L.$\times$P.grandidentata Michx. (줄기 절간조직 배양에 의한 교잡종 사시나무의 대량증식)

  • Sung Ho SON;Richard B. HALL
    • Korean Journal of Plant Tissue Culture
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    • v.22 no.3
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    • pp.131-135
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    • 1995
  • Physiologically modified stem nodes derived from ex vitro and in vivo explants of hybrid aspen (Populus alba L.X P.grandidentata Michx. 'Crandon') were tested for their multiple shoot regeneration capacity using a broad spectrum dosage of cytokinins. Ex vitro derived stem nodes with excised axillary buds at the time of culture produced 11 to 13 multiple shoots on 20 to 30 $\mu$M zeatin containing Woody Plant Medium (WPM) after 6 weeks. Excision of axillary bud sprouts after 2 weeks of culture and culture of the remaining stem nodes on WPM with 1.0 to 2.0 $\mu$M BA or 10 to 30 $\mu$M zeatin produced 13 to 15 and 7 to 8 shoots per explant, respectively, Multiple tiny shoots were produced when in vivo derived stem nodes (on which all leaves were removed) were cultured on WPM with 30 to 50 $\mu$M 2iP or 20 to 50 $\mu$M zeatin. The greatest number of multiple tiny shoot proliferation (32 to 50 shoots per explant) were obtained when the explants were cultured on media containing 20 $\mu$M zeatin. Successful transplanting of these multiple shoots into the greenhouse and/or nursery was achieved.

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Anti-Obestic Effects of Artemisiae Capillaris Herba, Artemisia Capillaris Stem Aqueous Extracts on the High Fat Diet Supplied Mice (고지방 사료 급여 마우스에서 인진쑥 추출물의 항비만 효과)

  • Kim, Hong-Tae;Kim, Dae-Dong;Ku, Sae-Kwang;Kim, Ju-Wan;Jang, Kwang-Ho;Oh, Tae-Ho;Lee, Keun-Woo
    • Journal of Veterinary Clinics
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    • v.27 no.4
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    • pp.348-365
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    • 2010
  • Artemisia capillaries THUNB is a perennial herb that belongs to the family compositae spp. and the most common plant among the various herbal folk remedies used in treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. The object of this study is to observe the dosage-dependent anti-obestic effects of an aqueous extracts of dried aqueous extracts of stems of Artemisia capillaris Thunberg. [Artemisiae capillaris Herba, In-Jin in Korean, INJ] on 45%/Kcal high fat diet (HFD) supplied mice. 45%/Kcal rodent HFD are supplied to ICR mice from 1 week before initiation of INJ administration throughout the 12 weeks, and after the end of 12 weeks of 62.5, 125 and 250 mg/kg/day of INJ administration, the efficacy was divided into five categories 1) hypoglycemic, 2) hepato-protective, 3) nephroprotective, 4) hypolipemic, and 5) anti- obesity effects. The effects were compared to those of simvastatin (for hypolipemic activity), silymarin (for hepatoprotective and free radical scavenger effects) and metformin (for hypoglycemic and related anti-obesity effects). 7 animals per group (8 groups; total 56adapted mice on HFD were selected base on the body weight at 6 days after initiation of HFD supply) were used in this experiment. INJ and all three different reference drugs were directly suspended or dissolved in distilled water, and administered at a volume of 10 mL/kg, once a day for 84 days from 1 week after HFD supply. As results of 91 days of continuous HFD supply, mice showed marked obese states, hyperglycemia, hyperlipemia, liver damages and kidney damages. These mean the obesity, diabetes, diabetic hepatopathies, nephropathies and hyperlipemia were induced by HFD supply. After end of 84 days of continuous treatment of three different dosages of INJ, all diabetes related complications were inhibited; relatively favorable anti-obesity, hypolipemic, hepatoprotective, hypoglycemic and nephroprotective effects. These favorable effects showed relatively good dose-relations between all three different dosages of INJ treated, and INJ 250 mg/kg showed enough favorable effects on diabetes and related four complications tested as compared with one of each three different references. Otherwise, the efficacy of 62.5 and 125 mg/kg of INJ was somewhat slighter than those of all three reference drugs. Therefore, the suitable effective dosage of INJ is considered as 250 mg/kg/day in the present study. The overall anti-obesity effects of INJ 250 mg/kg-treated group was similar or more favorable than those of metformin 250 mg/kg-treated group, and INJ 250 mg/kg showed slighter hypoglycemic effects with silymarin 100 mg/kg and metformin 250 mg/kg, similar hypolipemic effects with simvastatin 10 mg/kg, and similar hepatoprotective effects with silymarin 100 mg/kg, and similar nephroprotective effects with that of silymarin 100 mg/kg and metformin 250 mg/kg, respectively. Obese, hyperglycemia, hyperlipemia, steatohepatitis and related nephropathies induced by HFD supply were dramatically inhibited by 84 days of continuous treatment of all three different dosages of INJ. It is, therefore expected that INJ extracts will be a favorable alternative agent for diet-related diabetes and complications.