• Archives of Pharmacal Research
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• 제20권6호
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• pp.560-565
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• 1997

The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-.betha.-cyclodextrin $(2-HP{\beta}CD)$ vehicles were characterized. MT was endothermally decomposed as determined by differential scanning calorimetry (DSC). Melting point and heat of fusion obtained were $116.9{\pm}0.24^{\circ}C $.and $7249{\pm}217 cal/mol$., respectively. MT as received from a manufacture was very pure, at least 99.9%. The solubility of MT in PG solution increased slowly until reaching 40% PG and then steeply increased. Solubility of MT increased linearly as concentration of $2-HP{\beta}CD$ without PG INCREASED$(R^2=0.993)$. MT solubility in the mixtures of pg and $2-HP{\beta}CD$ also increased linearly but was less than the sum of its solubility in $2-HP{\beta}CD$ and PG individually. The MT solubility was low in water, simulated gastric or intestinal fluid but the highest in the mixture of PG(40v/v%) and $2-HP{\beta}CD$ (30w/v%) although efficiency of MT solubilization in $2-HP{\beta}CD$ decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics $(r^2>0.90)$. MT was unstable in strong acidic solution (HCl-NaCl buffer, pH 1.4) but relatively stable in other pH values of 4-10 at $70^{\circ}C$. In HCl-NaCl buffer, MT in 10% PG was more quickly degraded and then slowed dpwm at a higher concentration. However, the degradation rate constant of MT in 2-HP.betha.CD was not changed significantly when compared to the water. The current studies can be applied to the dosage formulations for the purpose of enhancing percutaneous absorption or bioavailability of MT.

• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.237-242
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• 2007

The chemical formula of indapamide is 3-(aminosulfonyl)-4-chloro-N-(2,3-dihydro-2-methyl-1H-indol-l-yl)-benzamide, Indapamide is an oral antipertensive diuretic agent indicated for the treatment of hypertensive and edema. Indapamide inhibits carbonic anhydrase enzyme. Transdermal drug delivery systems, as compared to their corresponding classical oral or injectable dosage form counterparts, offer many advantages. The most important advantages are improved systemic bioavailability of the pharmaceutical active ingredients (PAI), because the first-pass metabolism by the liver and digestive system are avoided; and the controlled, constant drug delivery profile (that is, controlled zero-order absorption). Also of importance is the reduced dose frequency compared to the conventional oral dosage forms (that is, once-a-day, twice-a-week or once-a-week). Other benefits include longer duration of therapeutic action from a single application, and reversible action. For example, patches can be removed to reverse any adverse effects that may be caused by overdosing. In order to evaluate the effects of vehicles and penetration enhancers on skin permeation of Indapamide, the skin permeation rates of Indapamide from vehicles of different composition were determined using Franz cells fitted with excised hairless skins. Solubility of Indapamide in various solvents was investigated to select a vehicle suitable for the percutaneous absorption of Indapamide, The solvents used were Tween80, Tween20, Labrasol, Lauroglycol90 (LG90) and Peceol. Lauroglycol90 increase the permeability of indapamide approximately 3.75-fold compared with the control. Tween80, Tween20, Labrasol, Lauroglycol90 (LG90) and Peceol showed flux of $0.06ug/cm^2/hr,\;0.4ug/cm^2/hr,\;0.21ug/cm^2/hr,\;0.72ug/cm^2/hr,\;0.29ug/cm^2/hr$, respectively.

• Archives of Pharmacal Research
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• 제19권2호
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• pp.116-121
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• 1996

Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choi et al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-.betha. mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-.betha., in wounded skin. PS-ODN were evaluated in vitro for skin penetration using normal and tape-stripped damaged rat skin. The in vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was $0.234{\pm}0.041{\mu}g/cm^2$ and that of tape-stripped damaged rat skin was $1.077{\pm}0.301{\mu}g/cm^2$ over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was $0.340{\pm}0.296{\mu}g/cm^2$ over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PSODN (25S) at 8hrs across damaged rat skin were $134.63{\pm}37.67{\mu}g/cm^2$ h, and $42.50{\pm}36.95ng/cm^2$ h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.

• 한국융합학회논문지
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• 제8권1호
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• pp.35-42
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• 2017

보름달 물해파리 유래 펩타이드인 LVH는 주름개선에 효과가 있는 기능성 소재로서 보고되어 있다. 본 연구에서는 LVH의 피부 침투 효율을 증가시키기 위하여 LVH와 팔미트산을 이용하여 pal-LVH를 합성하였고, 합성된 pal-LVH의 기능성 소재로서의 효과를 조사하였다. 이를 위해서 우리는 두 펩타이드의 세포독성, 항노화, 주름 개선 그리고 피부 자극에 대한 효능을 비교 평가하였다. Pal-LVH는 LVH와 마찬가지로 세포독성은 보이지 않았다. 그리고 고농도에서는 LVH와 비슷한 우수한 상처 치유와 항노화 능력을 보였고, 주름개선 효과 또한 저농도에서는 LVH와 거의 유사하게 나타났다. 이들 결과는 pal-LVH 펩타이드는 피부 침투율을 증가시키면서, LVH 펩타이드가 가지고 있는 우수한 효능에는 영향을 주지 않는다는 것을 지시한다. 따라서 pal-LVH는 주름개선 효과 및 안티에이징 물질 등의 기능성 신소재로서 가능성을 제시하며, 다양한 융합 연구를 통하여 의약품 개발에 응용되어 질 수 있다.

• 한국응용과학기술학회지
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• 제34권2호
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• pp.225-235
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• 2017

본 연구에서는 피부미백제로 개발된 레조시놀다이펜틸에터[1,3-di(pentyloxyl)benzene]를 함유하여 조성 상전이 방법(Phase Inversion Composition, PIC)방법으로 제조된 RS-Nanoemulsion의 경피 흡수 및 피부 미백 효능효과에 대해서 연구하였다. 지표성분인 1,3-di(pentyloxyl)benzene를 mineral oil에 용해한 대조시료와 일반 O/W유화법으로 제조된 RS-emulsion시료를 비교 대상으로 인체 피부에 대한 경피 흡수시험을 수행하였다. 시험결과, RS-Nanoemulsion 시료는 지표성분인 1,3-di(pentyloxyl) benzene를 mineral oil에 용해한 대조시료와 RS-emulsion 시료에 비해 통계적으로 유의하게 높은 지표성분 경피 투과율을 나타내었다. RS-Nanoemulsion을 O/W크림에 함유하여 만든 크림 제형의 피부임상시험을 통하여 그 유효성을 평가하고자 하였으며, 상기 시험결과 시험제품과 대조제품 모두 8주간의 시험기간에 특별한 이상반응이 관찰되지 않아 안전한 제품으로 확인되었고, 사용 8주 후 평가에서 대조제품 사용에 비해 시험제품이 통계적으로 유의한 수준으로 피부미백에 도움을 주는 효과가 있는 것을 확인하였다.

• 대한화장품학회지
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• 제31권3호
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• pp.245-251
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• 2005

화장품은 의약품과 달리 남녀노소를 불문하고 거의 평생에 걸쳐 사용하는 제품이므로 피부 및 인체의 안전성 확보는 중요한 문제라고 할 수 있다. 화장품의 안전성 평가는 화장품법에 식품의약품안전청장이 고시하도록 되어있어 현재 식약청고시 '기능성화장품등의 심사에 관한 규정'에서 정하고 있다. 자외선에 의한 피부독성은 피부노화, 피부홍반, 피부손상, 피부암 유발 면역계장애 등이 있으며, IARC (International agency for research on cancer)에서는 자외선을 사람에게 암을 유발하는 물질로 분류하고 있다. 자외선 노출에 의하여 설치류에 대한 피부암 유발보고는 많이 있고, 현재 전 세계적으로 자외선에 의한 피부 암화 과정에 대하여 활발한 연구가 진행되고 있다. 화장품이 광에 의한 영향을 평가하는 시험은 광독성시험으로, 국내에서 광독성에 대한 규정은 자외선에서 흡수가 없음을 증명하는 흡광도 시험자료를 제출하는 경우는 면제이고 그 외의 경우는 상기 고시에 의한 광독성 시험과 광감작성 시험을 실시하도록 되어 있다. 이 시험은 일반적으로 기니픽 또는 토끼를 포함한 적절한 동물로 실시하도록 규정되어 있다. 화장품 안전성 평가에 있어서 동물대체시험법의 요구는 3R (replacement, refinement, reduction) 운동으로 유럽을 중심으로 시작하여 이제는 전세계로 확대되어 있으며, 화장품 안전성심사에 있어 중요한 이슈로 대두되고 있다 화장품의 광독성 평가에 대한 대체시험법으로 3T3 NRU(neutral red uptake) 광독성시험이 2004년 4월 OECD 독성시험 기준으로 채택되었다. In vitro 광독성 시험법은 마우스 유래의 섬유아세포인 3T3 cell을 이용하여 광조사한 것과 광조사하지 않은 세포와의 세포독성을 NRU 시험을 이용하여 그 정도를 비교하여 그 차이(PIF, photoirritation factor)가 5배 이상이 되면 광독성 물질로 분류하는 평가방법이다.

• 약학회지
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• 제60권1호
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• pp.36-45
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• 2016

This study was aimed to enhance the percutaneous absorption of tizanidine hydrochloride (TZ) across Strat-M$^{TM}$ artificial membrane and excised hairless mouse skin using various vehicles and chemical permeation enhancers. Solubility studies were performed using hydrophilic and lipophilic vehicles. To initially evaluate vehicle effects on skin permeation, Strat-M$^{TM}$ membrane was adopted using Franz-type diffusion cells loaded with 0.4 mg donor dose. Effects of fatty acids on the permeation of TZ from PG and PGMC were compared, and the effects of various hydrophilic vehicles in the presence of linoleic acid were studied using excised hairless mouse skin specimens. The mean solubility (mg/ml) of TZ in hydrophilic vehicles was higher: water > PG > DMSO > ethanol > PEG 200 > NMP > PEG 300 > PEG 400 > DGME, and solubilities in lipophilic vehicles such as PGMC, PGMC, IPM, Captex 200 and Captex 300 were much less than 1.0 mg/ml. Permeation rates through StratTM membrane from pure vehicles were in the rank order: PGMC ${\geq}$ LBF > DMSO ${\geq}$ NMP ${\geq}$ PGML ${\geq}$ PG ${\geq}$ PEG 200 ${\geq}$ DGME ${\geq}$ EtOH. However, permeation rates of TZ through hairless mouse skin from pure vehicles were very low, although PG showed the highest flux ($1.66{\pm}0.28{\mu}g/cm^2{\cdot}hr$). Therefore, PG was selected in further studies. Addition of enhancers (3 v/v%) into PG markedly increased the flux (${\mu}g/cm^2{\cdot}hr$): oleyl alcohol ($14.9{\pm}3.1$) ${\geq}$ oleic acid ($14.5{\pm}1.6$) ${\geq}$ linoleic acid ($13.7{\pm}1.3$) > capric acid ($4.4{\pm}0.6$) > caprylic acid ($2.1{\pm}0.4$). Among hydrophilic vehicles with linoleic acid, PG and DMSO revealed relatively higher permeation for TZ. Increase of donor dose in PG resulted in dose-dependent permeation fluxes. These results suggest that permeation properties of TZ from nonaqueous solutions are markedly different between Strat-$M^{TM}$ membrane and excised hairless mouse skin, and transdermal delivery of TZ would be feasible with a combination of PG and enhancers.