• 폴리머
• /
• 제37권4호
• /
• pp.442-448
• /
• 2013

본 연구에서는 분무건조방법을 이용하여 고혈압 치료제로 사용되고 있는 난용성 약물인 에프로살탄의 고체분산체 제형을 다양한 조성 하에서 제조 및 평가하고, 효과적인 약물의 용해도 향상을 위한 제조 조건을 최적화하였다. 친수성 고분자 기제로 hydroxylpropylcellulose(HPC)와 poly(vinyl pyrrolidone)(PVP)를 사용하였고, 고분자 계면활성제로 poloxamer 407을 첨가하여 약물과 고분자의 다양한 조성비를 갖는 고체분산체를 제조한 후, 물리화학적 특성을 비교 평가하였다. 친수성 고분자의 조성비 증가와 함께 약물 결정성이 감소되었으며, HPC보다는 PVP가 약물과의 우수한 상용성을 바탕으로 결정화도 감소와 용출거동 개선 효과가 상대적으로 우수하였다. 친수성 고분자로 PVP를 사용한 경우 약물의 결정성이 대부분 사라져 고체분산체 내 대부분의 약물 분자들이 무정형으로 분산되어 있으며 약물의 용출률이 에프로살탄 대비 3~7배 이상 향상되었다.

• 약학회지
• /
• 제51권1호
• /
• pp.56-62
• /
• 2007

Twelve epoxy and hydroxydiosgenin derivatives (DI-1${\sim}$DI-12) were synthesized from diosgenin (25(R)-5-spirosten-3${\beta}$-ol). Diosgenin was epoxidized with m-chloroperoxybenzoic acid (mCPBA) to oxidize 25(R)-4${\alpha}$,5${\alpha}$-epoxyspirostane (DI-1). Diosgenin was reacted with DDQ to form 25(R)-1,4,6-spirostatrien-3-one (DI-2), which was treated with 30% H$_2$O$_2$ to give 25(R)-1${\alpha}$,2${\alpha}$-epoxy-4,6-spirostadien-3-one (DI-3) and treated with mCPBA to form 25(R)-6${\alpha}$,7${\alpha}$-epoxy-1,4-spirostadien-3-one (DI-7), respectively. DI-3 was reduced with NaBH$_4$ to afford 25(R) -1${\alpha}$,2 ${\alpha}$-epoxy-4,6-spirostadien-3${\beta}$-ol(DI-4) and reacted with Li metal in absolute ethanol to form 25(R)-2-ethoxy-1,4,6-spirostatrien-3-one (DI-5). DI-7 was reduced with NaBH$_4$ to produce 25(R)-3${\beta}$,7${\alpha}$-dihydroxy-4-spirostene (DI-8) and treated with Li metal in liquid ammonia to produce 25(R)-7${\alpha}$-hydroxy-4-spirosten-3-one (DI-9). DI-2 was reduced with NaBH$_4$ to form 25(R) -4,6-spirestadien-3${\beta}$-ol(DI-10), which was stirred with 30% H$_2$O$_2$ to synthesize 25(R)-4,6-spirostadien-3-one (DI-11) and reacted with mCPBA to give 25(R)-4${\beta}$,5${\beta}$ -epoxy-6-spirosten-3${\beta}$-ol (DI-12), respectively. The antinociceptive effects of synthesiz ed compounds were measured by hot plate method and compound DI-7 signifcantly exhibited antinociceptive effect. DI-2 decreased the serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.

• Archives of Pharmacal Research
• /
• 제29권10호
• /
• pp.928-933
• /
• 2006

Percutaneous delivery of NSAIDs has advantages of avoiding hepatic first pass effect and delivering the drug for extended period of time at a sustained, concentrated level at the inflammation site that mainly acts at the joint and the related regions. To develop the new topical formulations of pranoprofen that have suitable bioadhesion, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer 407. The effects of temperature on drug release was performed at $32^{\circ}C$, $37^{\circ}C$ and $42^{\circ}C$ according to drug concentration of 0.04%, 0.08%, 0.12%, 0.16%, and 0.2% (w/w) using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. The increase of temperature showed the increased drug release. The activation energy (Ea), which were calculated from the slope of lop P versus 1000/T plots was 11.22 kcal/ mol for 0.04%, 10.79 kcal/mol for 0.08%, 10.41 kcal/mol for 0.12% and 8.88 kcal/mol for 0.16% loading dose from the pranoprofen gel. To increase the drug permeation, some kinds of penetration enhancers such as the ethylene glycols, the propylene glycols, the glycerides, the non-ionic surfactants and the fatty acids were incorporated in the gel formulation. Among the various enhancers used, propylene glycol mono laurate showed the highest enhancing effects with the enhancement factor of 2.74. The results of this study suggest that development of topical gel formulation of pranoprofen containing an enhancer is feasible.

• Journal of Pharmaceutical Investigation
• /
• 제39권4호
• /
• pp.249-255
• /
• 2009

The main object of this study was to prepare of w/o emulsion including glyceryl monooleate(GMO) and to evaluate its stability by using the recently developed $Turbiscan^{(R)}LAB$. GMO is the polar oily surfactant with the low HLB value, and it forms the gel phase of cubic structures after dissolves in aqueous media. Phosphate buffer solution (PBS) of pH 7.4 was prepared as the water phase and Marcol 52(mineral oil) was used as the oil phase in this study. GMO was used as the surfactant of W/O emulsion. W/O emulsion using GMO alone as a surfactant was very unstable. But the emulsion using both GMO and poloxamer 407 was more stable. The stability of W/O emulsions was evaluated after centrifuging the emulsions. But it was difficult with naked eye because an opaque and concentrated system like W/O emulsion was very turbid. So $Turbiscan^{(R)}LAB$ was used to detect the destabilization phenomena in non-diluted emulsion. As a result, the W/O emulsion using the proper amounts of GMO and poloxamer 407 was more stable among them using GMO of various amounts. But it seems that the other element for the stability of W/O emulsion including GMO was required. Furthermore, the $Turbiscan^{(R)}LAB$ was a very efficient analyzer for evaluating the physical stability of emulsion.

• 한국식품영양과학회지
• /
• 제37권6호
• /
• pp.708-713
• /
• 2008

명일엽 및 울금의 혼합사용이 고지혈증 개선에 효과가 있는 지를 규명하기 위하여 고콜레스테롤식이를 이용한 고콜레스테롤혈증과 poloxamer 407(P-407)의 복강투여로 유도한 고중성지질혈증에서 명일엽과 울금 추출물의 단독 또는 혼합투여 시 혈중 지질에 미치는 효과를 비교 분석하였다. 고콜레스테롤식이로 유도한 고콜레스테롤혈증 쥐에서 총 콜레스테롤 농도는 음성대조군에 비하여 명일엽군은 6.8%, 울금군은 22.1%, 복합조성물군은 28.2%의 감소효과를 보였다(p<0.001). HDL-콜레스테롤 농도는 실험군 간에 유의적인 차이를 보이지 않았다. LDL-콜레스테롤 농도는 음성대조군에 비교하여 명일엽군은 9.8%, 울금군은 28.8%, 복합조성물군은 35.6%의 감소효과를 보였다(p<0.001). 동맥경화지수(AI)와 심혈관 위험지수(CRF)는 음성대조군에 비하여 울금군 및 복합조성물군에서 유의적으로 감소하였다(각p<0.001). 간기능을 나타내는 GOT의 활성은 음성대조군에 비하여 울금군과 복합조성물군이 유의적으로 감소하였고, 특히 울금군의 감소폭이 커 정상대조군 수준까지 저하되었다(p<0.001). P-407로 유도한 고중성지방혈증 쥐에서 혈청 중성지방농도는 음성대조군에 비하여 명일엽 추출물의 경우 17.2%, 울금 추출물의 경우 19.7%가, 복합조성물 48.3%의 감소효과를 나타내었다. 이상의 결과를 요약할 때 명일엽과 울금의 복합추출물은 식이로 유도한 고콜레스테롤혈증 쥐에서 총 콜레스테롤, LDL-콜레스테롤, AI, CRF의 감소효과를 보였고, P-407을 이용하여 유도한 고중성지방혈증 동물모델에서도 중성지방의 유의적인 감소효과를 보였다. 이러한 효과는 울금과 명일엽의 단독투여에 비하여 감소폭이 더 큰 것으로 나타나 이들을 조합한 새로운 기능성식품의 개발의 기초자료로 활용될 수 있을 것으로 사료된다. 그러나 본 연구는 복합추출물의 단일농도 투여에 의한 혈중지질의 개선효과를 확인하는데 그쳤으므로, 향후 이들의 효과적인 투여농도와 작용기전을 밝힐 수 있는 계속적인 연구가 이루어져야 할 것으로 생각된다.

• 한국식품영양과학회지
• /
• 제40권4호
• /
• pp.531-537
• /
• 2011

본 연구는 일상에서 우리가 쉽게 접할 수 있는 꽁치로 동물실험을 통해 항고지혈증 및 항동맥경화증의 효과를 검증 하였다. 실험동물에게 1% cholesterol과 0.5% Na-cholic acid를 첨가하여 인위적으로 고지혈증을 유발시킨 후 꽁치의 전체, 육, 내장, 머리+꼬리+뼈의 4종류로 나눈 분획을 경구투여 하여 항고지혈증 및 항동맥경화증의 효과를 살펴본 결과, 정상군에 비해 poloxamer-407을 투여하여 고지혈증을 유발한 흰쥐의 중성지방의 함량이 현저하게 감소하였다. 또한 poloxamer-407에 의한 고지혈증의 경감효과를 재확인할 목적으로 Triton WR-1339를 투여한 결과도 역시 중성지방의 함량이 현저하게 감소하였다. 이러한 결과를 기초로 4종류의 분획 중 다른 시료보다 육분획에서 대조군에 비해 지방조직, 혈청 지질량, 혈청 콜레스테롤 함량, 동맥경화지수, 간조직중의 지질 및 콜레스테롤의 함량, 분변 중의 지질의 함량 등이 현저하게 감소하였다. 혈중 지질과산화와 활성산소의 양은 현저하게 감소하지 않았지만, 활성산소를 제거하는 SOD의 양은 32.5%만큼 현저하게 증가한 것으로 보아 꽁치 육분획에서 항고지혈증 및 항동맥경화증의 효과가 탁월함을 알 수 있었다. 이상의 결과로부터 꽁치육의 항고지혈증 및 항동맥경화증의 효과를 확인할 수 있었다. 하지만 구체적으로 꽁치육의 어떠한 성분이 항고지혈증 및 항동맥경화증의 효과를 나타내는 지에 대해서는 추가 실험을 해볼 필요가 있다.

• Journal of Pharmaceutical Investigation
• /
• 제30권3호
• /
• pp.167-172
• /
• 2000

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.

• Biomolecules & Therapeutics
• /
• 제6권2호
• /
• pp.213-218
• /
• 1998

A novel in situ-gelling and mucoadhesive acetaminophen liquid suppository was developed to improve the patient compliance of conventional solid suppository. In this study, acetaminophen liquid suppository, Likipe $n_{R}$, ［aminophen/Poloxamer 407/Poloxamer 188/so4ium alginate (5/15/19/0.6%)] with relation temperature at 30-36 "C and suitable gel strength and bioadhesive force, dissolution pattern similar to conventional solid type suppository, Suspe $n_{R}$, was developed. Furthermore, the bioequivalence of two acetaminophen products was evaluated in 16 normal male volunteers (age 22-27 yr, body weight 56-72 kg) following sidle rectal administration. Test product was Likipe $n_{R}$ suppository (Dong-Wha Pharm. Corp., Korea)and reference product was Suspe $n_{R}$204-212 suppository (Hanmi Pharm. Corp., Korea). Both products contain 125 mg of acetaminophen. Four Suppositories of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of acetaminophen was accomplished using HPLC. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{-2}$4h/) (30.14$\pm$8.64 vs 27.98$\pm$ 6.53 $\mu$g .h/ml), maximum plasma concentration ( $C_{max}$) (3.29$\pm$0.87 vs 3.60$\pm$0.66 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.91 $\pm$0.55 vs 2.69$\pm$0.60 h). The differences of mean AUCo $_{24h}$, C-a. and T-between the two products (7.18%, 9.58% and 7.53%, respectively) were less than 20%. The power (1-7) and treatment difference ($\Delta$) for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ were more than 0.8 and less than 0.2, respectively at $\alpha$=0.1. The confidence limits for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ (-0.81 ~13.55%, -1.56~ 17.60 and -3.81 ~18.87%, respectively) were less than $\pm$ 20% at $\alpha$=0.1. These results suggest that the bioavailability of Likipe $n_{R}$ suppository is not significantly different from that of Suspe $n_{R}$ suppsitory. Therefore, two products are bio-equivalent based on the current results.results.lts.sults.results.lts.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2005년도 춘계 학술발표대회
• /
• pp.5-16
• /
• 2005

The herb of Allium victorialis var. platyphyllum (Liliaceae) has been used as an edible wild herb and to treat heart failure and gastritis. We have already reported antihyperlipidemic anti-tumor effects of this plant. To enlarge the commercial availability of this food, it was investigated whether the extracts of A. victorialis var.platyphyllum reduce hyperlipidemia and obesity or not. The plants tested in this experiment were collected from two eco-types of IS. Ullung and Mt. Odae cultivated at Pyongchang. Extracts were prepared by extracting the fresh leaves and those dried at $36^{\circ}C$ and $90^{\circ}C$, respectively. Pretreatment with the ethanolic extracts for two weeks (p.o.) reduced serum triglyceride-, total cholesterol- and LDL-cholesterol contents in rats induced by Triton WR-1339, respectively. Furthermore, oral administration of the extracts also inhibited the hyperlipidemia induced with oral diet of 30% corn oil. In the other attempt to find to alleviate the obesity, the model rats with obesity were induced by the high fat-diet for six weeks. Post-treatment with the extracts for two weeks significantly reduced the hyperlipidemia. Retroperitoneal-, epidymal- and total abdominal fat pad weights were considerably reduced at 100 mg/kg oral administration of the extracts. Increased feces lipid contents were also found in the rat treated with the extracts. The extract of Mt. Odae eco-type showed more potent activity than that of Is. Ullung one. These results suggest that use of the fresh leaves may lead to the higher activity in treatment of hyperlipidemia and obesity than of the dried one.

• 생약학회지
• /
• 제37권3호
• /
• pp.190-195
• /
• 2006

Obesity is associated with a number of pathological disorders such as non-insulin-dependent diabetes, hypertension, hyperlipidemia, and cardiovascular diseases. Bangpoongtongsungsankamibang (BTSK) has been widely used in the oriental medicine for the treatment of several diseases associated with inflammatory abnormalities in cardiovascular and nervous system. The BTSK is the modified prescription of Bangpoongtongsungsankamibang in which sea tangle (Laminaria japonica) were added. This study was carried out to detemine the anti-obestic effects of BTSK. Pretreatment with the BTSK at daily dose of 100 or 200 mg/kg (p.o.) far 4 weeks reduced serum triglyceride, total cholesterol contents in rat induced by Poloxamer-407 or Triton WR-1339, respectively. Furthermore, post-treatment with BTSK far four weeks also inhibited body weight gain, adipose tissue mass and hyperlipidemia induced by the high fat diet for six weeks. The BTSK shifted serum total-, HDL- and LDL-cholesterol levels toward the values of normal group, suggesting that BTSK has hypolipldemlc effects. The rats fed BTSK reduced lipid peroxide and hydroxy radical in the rat blood and increased superoxide dismutase (SOD) activity compared to the control group. Taken together, these results superoxide that BTSK improve hyperlidemia and obesity via the upregulation of anti-oxidative mechanism.