• Journal of Pharmaceutical Investigation
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• 제41권1호
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• pp.9-17
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• 2011

The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.91-100
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• 2010

The objective of this work is to study transdermal delivery of donepezil hydrochloride (DH) using iontophoresis and to evaluate various factors which affect the transdermal transport. After the flux study using 4 kinds of hydrogel, hydrogel containing 8% poly(ethylene oxide) (PEO) was chosen as the hydrogel for further studies. Under experimental condition, DH was stable. We have studied the effect of polarity, current density, drug concentration and current profile on transdermal flux and compared the results. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. DH is positively charged at pH 7.4, and anodal delivery was much larger than cathodal and passive delivery at all current densities studied (0.2, 0.4 and 0.6 mA/$cm^2$). Cathodal delivery showed higher flux than passive flux. Flux increased as the concentration of DH in hydrogel increased. Pulsatile application of current showed smaller flux value than the application of continuous current. Based on these results, we have evaluated the possibility of delivering enough amount of DH to reach the therapeutic level. The maximum cumulative amount of DH transported for 12 hours was 455 ${\mu}g/cm^2{\cdot}hr$ when the amount of DH in the hydrogel was 3 mg/mL and the current density was 0.4 mA/$cm^2$. If the patch size is 10 $cm^2$, then we can deliver 4.6 mg for 12 hours. Because the daily dosage of DH is 5 mg, it seems possible to deliver clinically effective amount of DH using iontophoresis. This study also provides some information about the role of electrorepulsion and electroosmosis during the transport through skin.

• 대한정형외과학회지
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• 제54권5호
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• pp.411-417
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• 2019

목적: 슬관절 인공관절 전치환술(total knee arthroplasty, TKA) 시행 후 일회 주사 내전근관 차단술(single injection adductor canal block, SACB), 지속적 내전근관 차단술(continuous adductor canal block, CACB), 그리고 경피성 buprenorphine 병합 사용을 통한 임상결과를 비교하였다. 대상 및 방법: TKA 후 통증 조절을 시행한 125명의 환자들을 대상으로 SACB를 단독 시행한 I군(41명), SACB 및 경피성 buprenorphine 10 ㎍/h를 병합 사용한 II군(44명), CACB를 시행한 III군(40명)으로 분류하여 임상결과를 후향적으로 비교하였다. 통증 조절 지표로 visual analogue scale (VAS)을 사용하였으며, 술 후 12시간, 24시간, 48시간째 침상 안정 상태에서의 VAS (VAS-Rest)와 술 후 24시간 및 48시간째 continuous passive motion (CPM) 중 VAS (VAS-CPM), 그리고 술 후 48시간 동안 정맥주사 patient controlled analgesia (PCA)를 위한 약물(부토판, 트리돌, 케토락)의 사용량을 측정하였다. 기능 개선 지표로 술 후 48시간 동안 오심 및 구토 증상 횟수, 술 후 24시간 및 48시간째 최대 슬관절 굴곡 범위와 최대 자가 보행 거리, 그리고 총 재원 기간을 기록하여 비교하였다. 결과: VAS-Rest는 술 후 12시간째는 유의한 차이가 없었으나 술 후 24시간 및 48시간째와 VAS-CPM, PCA 총 사용량에서 II, III군이 I군보다 유의하게(p<0.05) 더 낮은 결과를 나타내었다. 그리고 오심 및 구토 증상 횟수, 최대 슬관절 굴곡 범위와 자가 보행 거리, 총 재원 기간은 세 군 간의 유의한 차이를 보이지 않았다. 결론: SACB 및 경피성 buprenorphine 병합 사용은 초기 통증 조절에 우수한 결과를 보였으며, 카테터로 인한 문제가 없고, 사용의 편의성 및 신 기능에 대한 안전성이 있기 때문에 TKA 후 유용한 통증 조절 방법이 될 수 있다.

• 생명과학회지
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• 제24권4호
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• pp.437-446
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• 2014

트립탄 계열의 약물을 경구 복용 시에 트립탄은 소화 시스템에 의하여 생물학적 이용도가 감소되며, 혈중 약물 농도가 시간의 경과에 따라 급격히 감소되고, 위장 장애의 가능성 등이 있다는 문제들을 나타낸다. 일반 겔 패치의 부작용을 개선하기 위하여 패치는 하이드로겔 형태로 제조하였다. 하이드로겔 패치의 주가 되는 메트릭스의 고분자는 PVA를 사용하였고, PEG는 PVA의 분자 간/분자 내 수소결합을 유도하기 위해 첨가물로서 사용되었고 알모트립탄 약물이 부가되었다. 또한 PVA 체인간의 미세 상분리를 가속하기 위해 매우 낮은 온도에서 액체질소가 사용되었다. FT-IR 분석에서 PVA, PEG 그리고 알모트립탄의 흡수 밴드를 확인하였다. PEG 함량이 증가함에 따라 결정화도, 수분흡수력과 인장강도들은 증가하였다. 약물방출 실험에서 약물 방출량은 PEG의 함량이 높은 하이드로겔이 약물 방출 시에 팽윤이 더 잘 이루어져 증가하였다. 본 실험에서 10 wt%의 PEG를 첨가하여 제조된 하이드로겔의 약물 방출량이 가장 좋았다. 또한 10 wt%의 PEG가 함유된 하이드로겔은 2시간째까지 전체 약물의 약 60%가 방출됨을 확인하였고, 24시간째까지도 방출이 계속되었다. 따라서 제조된 하이드로겔은 triptan의 1차 투여 이후 24시간 이내에 재발하는 편두통 환자들을 대상으로 한 트립탄의 2차 투여를 위한 경피흡수형 패치로서 적합하다.

• The Korean Journal of Pain
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• 제6권2호
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• pp.231-236
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• 1993

Clonidine, a centrally-acting antihypertensive agent known to reduce central sympathetic outflow and modulate presynaptic transmitter's release, has shown to suppress central noradrenergic hyperactivity induced by immobilization stress in animals, by decreasing the MAC of halothane and the dose of narcotics required to prevent reflex cardiovascular response to noxious stimuli, and to have potent analgesic properties in humans. These characteristics suggest that clonidine might be a useful adjunct to the anesthetic management of patients with preexisting hypertension. Accordingly, we determined the clinical efficacy and safety on analgesia, sedation and hemodynamic stability in the perioperative period. Thirty patients(ASA physical status II-III) with a history of arterial hypertension, scheduled for elective orthopedic surgery were randomly assigned to two groups. We applied CPA-clonidine patch($6.9\;mg/cm^2$, 0.2 mg delivered daily) or placebo patch to each groups, 48 hours prior to induction of anesthesia. Antihypertensive medication was continued until the morning of the scheduled surgery. All patients received premedication of atropine and lorazepam, and induced anesthesia with thiopental and succinylcholine, and maintained with enflurane and 50% nitrous oxide, while sustaining the BP and pulse rate at acceptable range. For the relief of pain postoperatively, diclofenac and fentanyl were administered intramuscularly on demand. The results were as follows: 1) The change of hemodynamic responses in clonidine group was less compared to the placebo group. 2) Intraoperative anesthetic requirement for enflurane in clonidine group were significantly lower than placebo group. 3) Postoperative analgetic requirement in clonidine group were significantly lower than placebo group. In clonidine group, 5 cases out of 15 cases were required no analgetics, and the incidence of administration of additional fentanyl was decreased to 5 cases, comparing with 10 cases in placebo group.

• The Korean Journal of Pain
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• 제22권2호
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• pp.130-134
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• 2009

Background: The advances in surgical technology, anesthesia and perioperative care have made it possible to perform laparoscopic cholecystectomy on an outpatient basis. This study was conducted to assess the analgesic effect and the adverse events of different dosing methods when using transdermal fentanyl patches (TDFPs) after laparoscopic cholecystectomy. Methods: Sixty patients who were to undergo laparoscopic cholecystectomy under general anesthesia were divided into two groups. Group 1: 2 TDFPs that released $12{\mu}g/h$ were applied after the induction of anesthesia and these 2 patches were removed after 24 hours. Group 2: 2 TDFPs that released $12{\mu}g/h$ were applied after the induction of anesthesia and one patch was removed after 7 hours and the other patch was removed after 24 hours. The intensity of the postoperative pain was assessed by using a visual analogue scale (VAS) and assessing the adverse events, including dizziness, pruritus and nausea/vomiting, were recorded for 48 hours postoperatively. Results: The VAS score of postoperative pain was not significantly different between the two groups at all times. The incidence of dizziness in groups I and II was 10 and 3, respectively, and the incidence of nausea/vomiting in group I and II was 4 and 0, respectively. The incidences of dizziness and nausea/vomiting in group II were significantly lower than those of group I (P<0.05). Conclusions: A dosing method that removes half of the TDFPs ($24{\mu}g/h$) after 7 hours of application caused a lower incidence of dizziness and nausea/vomiting without any significant difference of postoperative analgesic efficacy, as compared to leaving on both the TDFPs (24$\mu$g/h) for 24 hours after laparoscopic cholecystectomy.

• Toxicological Research
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• 제29권2호
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• pp.87-90
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• 2013

The potential role of topical valproate (VPA) in hair regrowth has been recently suggested. However, safety reports of VPA as a topical formulation are lacking. Therefore, in the present study, we investigated whether VPA causes skin irritation in humans. We first performed a cell viability test and showed that VPA did not exhibit toxicity toward HaCaT keratinocytes, fibroblasts, and RBL-3H mast cells. We then performed clinical patch test and skin irritation test through transdermal drug delivery with the help of microneedle rollers. No significant findings were obtained in the clinical patch test. In the skin irritation test, only 1 patient showed erythema at 1 hr, but the irritation reaction faded away within a few hours. Erythema and edema were not observed at 24 hr. We concluded that VPA has minimal potential to elicit skin irritation. Therefore, we consider that VPA can safely be applied to human skin.

• Child Health Nursing Research
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• 제26권4호
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• pp.434-444
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• 2020

Purpose: The aim of this retrospective study was to analyze the characteristics of peripheral arterial ischemia and tissue necrosis in premature babies, as well as the effects of nitroglycerin. Methods: In total, 513 newborns were enrolled who were admitted to the neonatal intensive care unit with a gestational age of 34 weeks or younger. Data were collected on general personal and clinical information, peripheral arterial ischemia, and nitroglycerin patch application in the premature infants. The collected data were analyzed using the χ² test, t-test, Mann-Whitney U test, logistic regression. Results: Thirty-six (7.0%) infants had peripheral arterial ischemia, while 477 (93.0%) infants did not. Lower gestational age (χ²=35.97, p<.001), lower birth weight (χ²=29.40, p<.001), lower blood pressure (χ²=23.10, p<.001), and insertion of an umbilical artery catheter (p<.001) were significantly associated with the occurrence of peripheral arterial ischemia. Among the preterm infants in whom nitroglycerin patches were applied, 30 (83.3%) premature infants without necrosis improved without complications, 4 (11.1%) showed hypotension, and 2 (5.6%) showed skin damage. Conclusion: Based on a review of our experiences with nitroglycerin patches, we recommend closely observing skin color and using nitroglycerin patches on the skin to help improve flow in premature infants with peripheral arterial ischemia.

• 대한수의학회지
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• 제48권4호
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• pp.481-487
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• 2008

A 17-month-old intact male Cocker Spaniel was presented with primary complaints of severe ascites, exercise intolerance, and diarrhea. Diagnostic studies revealed tricuspid and pulmonic regurgitation on phonocardiogram, right ventricular enlargement on the electrocardiogram, typical right cardiac enlargement signs on the thoracic radiography and tricuspid valve malformation and marked enlargement of the right atrium and right ventricle on the echocardiography and tricuspid and pulmonary regurgitation on the color spectral echocardiography, suggesting tricuspid valve dysplasia and pulmonary hypertension. Using angiography and cardiac catheterization, pulmonary hypertension was ruled out. Further echocardiographic study revealed membranous valvular structures cranial to pulmonary annulus causing pulmonary regurgitation. Based on these findings on the diagnostic investigation, the case was diagnosed as tricuspid valve dysplasia complicated with pulmonic regurgitation. The dog was medically managed with furosemide, enalapril, nitroglycerine transdermal patch and pimobendan after the ascitic fluid removal.

• 대한화장품학회지
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• 제33권1호
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• pp.23-28
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• 2007

비타민 C는 강력한 환원제로서 멜라닌 색소의 합성을 저해하는 것으로 알려져 있다. 그러나 일반적인 화장품 제형에서는 낮은 안정성과 경피 흡수의 문제점으로 만족할 만한 효과를 나타내지 못한다. 본 연구에서는 안정성이 개선된 비타민 C의 유도체인 ascorbyl glucoside (AsAG)을 유효성분으로 하여 경피흡수를 증가시키고자 하였다. 본 실험에서는 유연하면서도 박막 형태의 배터리를 장착한 패치 화장품을 제조하고 안정성과 경피흡수성을 평가하였다. 피부에 낮은 전류를 증가하는 이온토포레시스를 활용하여 피부에 적용하는 전류의 세기를 증가시키면 물질의 경피흡수는 증가한다. 그러나 전류의 세기를 증가시키면 피부 부작용이 증가하기 때문에 본 연구에서는 한국인의 피부에 맞는 적절한 전류를 선택하여 피부 부작용을 최소화하였다. 이런 결과들을 바탕으로 유연하면서도 가벼운 박막 배터리를 개발하였으며, 2%의 AsAG을 함유한 이온토포레시스 패치의 안전성, 경피흡수정도, 미백효과 등을 검토한 결과 피부에 가하는 최적의 전류는 1.5 V의 배터리를 사용하여 피부 부작용과 경피흡수를 고려하여 평균 0.1 mA이었다. 또한 패치의 임상실험 결과 유의한 수준의 미백효과를 보였으며 피부 자극도도 통상의 화장품 수준을 나타냈다.