• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.173-179
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• 2002

Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm $({\Delta}H)$ of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas ${\Delta}H$ of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.

• 대한치과교정학회지
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• 제35권4호
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• pp.275-285
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• 2005

본 연구는 ipriflavone(isopropoxysioflavone)의 투여가 백서 두개관세포의 증식과 골조직 개조에 미치는 영향을 알아보고자 시도되었다. 태령 20-21일째의 백서 두개관세포를 분리 배양한 후, $10^{-9}M$부터 $10^{-5}M$까지 농도의 ipriflavone을 투여하고 1일째와 3일째에 MTT분석을 시행하여 흡광도를 평가한 결과, 모든 농도에서 백서 두개관세포의 증식을 보이지 않았다. 한편 골조직 개조에 미치는 영향을 알아보기 위하여 14일째에 alizarin red 염색을 시행하여, 형성된 석회화 결절 면적을 측정하였을 때, $10^{-8}M,\;10^{-7}M,\;10^-6}M$농도를 투여한 경우 석회화 결절 형성이 유의하게 증가하였다 골아세포의 분화에 미치는 영향을 알아보기 위하여 ipriflavone을 투여하고 7일째와 14일째에 추출한 RNA를 역전사 중합효소 연쇄반응(RT-PCR)을 시켜 bone sialoprotein(BSP), type I collagen(COL I) osteocalcin (OCN) 유전자 발현을 관찰한 결과 BSP와 COL I 유전자는 배양 7일째 높은 발현을 보였고, OCN 유전자는 배양 14일째 높은 발현을 보였다. 이상의 연구결과 ipriflavone이 백서 두개관세포에서 석회화를 촉진시키고 골아세포의 분화에 관여하는 BSP, COL I 및 OCN 유전자 발현을 증가시켜 골조직의 개조를 빠르게 할 수 있음을 시사하였다.

• 대한치과교정학회지
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• 제38권5호
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• pp.347-357
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• 2008

본 연구는 치아이동 후 ipriflavone 투여가 치주조직의 재형성, 나아가 치아회귀 억제에 미치는 영향을 알아보기 위하여 시행되었다 웅성 백서 72마리를 대상으로 상악 좌우측 제1, 2구치 사이에 교정용 고무밴드를 끼워 제1, 2구치를 3주간 이동시킨 다음, 교정용 고무밴드 제거 1일 전부터 매일 체중 kg당 50 mg 또는 400 mg의 ipriflavone을 투여한 실험군과 ipriflavone을 투여하지 않은 대조군으로 구분하였다. 교정용 고무밴드를 제거함으로써 회귀가 나타나기 시작한 날로부터 5일 간격으로 15일까지 각각 실험동물을 희생시켜가며 치아회귀 거리를 계측하는 한편 치주조직 재형성 소견을 관찰하였다. Ipriflavone을 투여하고 치아회귀를 관찰한 결과 용량에 관계없이 대조군에 비하여 적은 양의 회귀를 나타내었으며 시간 간격에 따른 치아회귀를 관찰한 결과 대부분의 회귀가 5일째 나타난 대조군과 달리, 늦게 그리고 점진적으로 나타나는 양상을 보였다. Iprinavone을 투여하고 조직소견을 관찰한 결과 대조군에 비하여 치조골연이 매끄러운 양상을 보였으며 시간 간격에 따른 조직소견을 관찰한 결과 대조군에 비하여 치주인대 재배열이 빠르게 나타나는 양상을 보였다. 이상의 결과는 ipriflavone의 투여가 치주조직의 재형성을 통하여 회귀를 억제함으로 교정적 치아이동 후 보정에 도움이 될 수 있음을 시사하였다.

• Journal of Pharmaceutical Investigation
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• 제35권1호
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• pp.1-5
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• 2005

ABSTRACT -Ipriflavone is a synthetic flavonoid derivate that improves osteoblast cell activity inhibiting bone resorption. In order to improve the bioavailability, solid dispersions of ipriflavone with PVP (poly-N-vinylpyrrolidone, MW=40,000 g/mole) were prepared by a spray-drying method. During the manufacturing of solid dispersion, various solvents [ethanol (EtOH), acetonitrile, methylene chloride and cosolvent-EtOH:acetone=1:1] were used to dissolve the ipriflavone and PVP. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to evaluate the physicochemical interaction between ipriflavone and PVP. Particle size, crystallinity and the area of the endotherm $({\Delta}H)$ of solid dispersed ipriflavone using the acetonitrile as solvent were much smaller than those of the other preparation types. Bioavailability of ipriflavone in vivo was changed by solvents. When considering the result of in vivo test, solid dispersion of ipriflavone using the acetonitrile as solvent showed the best choice.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제19권4호
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• pp.395-398
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• 1997

Ipriflavone(IP)은 골흡수 억제효과에 골형성 촉진효과를 지니는 약물로 보고되어 왔다. 이러한 IP의 특성때문에 골의 치유를 촉진시키기 위한 약물로서 구강외과 영역에서 쓰일 수도 있으리라 생각되었다. 이에 저자는 그동안 보고되어온 IP의 골 형성 촉진효과가 실제로 나타나는지를 확인하고 또한 어떤 농도에서 나타나는지를 알아보기위해 IP를 서로다른 농도로 하여 골세포주(MC3T3-El cell line)의 배지에 넣은후, 골 형성의 지표로 쓰일수있는 collagen합성정도를 보고자 하였으며 이 자료를 앞으로서 in vivo 동물실험 연구의 기초자료로 사용코자 하였다. 본 연구에서 IP의 골형성 촉진효과를 collagen 합성정도를 측정을 통해 확인하였고, 특히 IP이 $10^{-7}M$농도일때 현저한 collagen합성의 증가를 관찰 하였으며 앞으로의 동물실험등을 통해 구강외과 영역에서의 사용가능성에 대해 좀더 연구해 보고자 한다.

• 한국동물위생학회지
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• 제23권3호
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• pp.235-245
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• 2000

This study was peformed to elucidate the effects of antler, red ginseng, safflower seed, ipriflavone and estrogen on ovariectomized rats. The rats were fed with Ca and P deficient diet for five weeks to induce osteoporosis. After this period, these animals were fed with normal for and treated every other day with antler(600mg/kg, PO), red ginseng(200mg/kg, PO), safflower(200mg/kg, PO), ipriflavone(80mg/kg, PO) and estrogene(400$\mu\textrm{g}$/kg, IM) for S weeks. During the treatment, the rats were examined for body, organ, femur and femur ash weights. And electron-microscopical examinations were also performed on femora. The results are summarized as follows : 1. The body weights of the antler, red ginseng, safflower, ipriflavone and estrogen-treated groups after five weeks of treatment, were 303.0$\pm$3.0g, 273.3$\pm$4.4g, 288.3$\pm$5.1g, 300.5$\pm$5.2g, 320.5$\pm$4.2g, respectively. They, except the red ginseng-treated group, were significantly higher than 278.4$\pm$2.7g of normal control group(P<0.05). And the body weight of non-treatment group was 29it.2$\pm$5.5g which was higher than that of control group, too. 2. The weights of left femur after five weeks of treatment were showed 0.83$\pm$0.2g by antler, 0.89$\pm$0.2g by red ginseng, 0.87$\pm$0.2g by safflower 0.83$\pm$0.1g by ipriflavone and 0.78$\pm$0.1g by estrogen-treated group. They were a little lower than 0.97$\pm$0.1g of normal control group. Non-treatment group showed 0.83$\pm$0.1g which was lower than that of control group but not significant. 3. The weights of ashed left femora after five weeks of treatment were showed 0.36$\pm$0.01g by antler, 0.40$\pm$0.01g by red ginseng, 0.41$\pm$0.01g by safflower, 0.36$\pm$0.01g by ipriflavone and 0.35$\pm$0.01g by estrogen-treated group. Those results were significantly lower than 0.43$\pm$0.01g of normal control group. And non-treatment group showed 0.29$\pm$0.01g of femoral ash which was significantly lower than that showed by control group(p<0.05). 4. The femoral Ca contents of the antler, red ginseng, safflower, ipriflavone and estrogen-treated rats were 19.6$\pm$0.7%, 17.8$\pm$1.1%, 18.8$\pm$0.9%, 18.0$\pm$1.1%, 15.3$\pm$1.1%, respectively, after five weeks of treatment. The femoral Ca contents of antler and safflower-treated groups were higher than that of control group which showed 18.2$\pm$0.9% of Ca The non-treatment group, showing 15.3$\pm$0.7%, had significantly lower content of Ca than normal group(p<0.05). 5. The weights of liver, spleen, and kidney in the osteoporosis-induced rats during the treatment with antler, red ginseng, safflower, jpriflavone and estrogen showed not significant changes. 6. The connections among the trabeculae of control group were maintained well, showing no bone loss. However, the connections among the trabeculae of non-treatment group were thinner than those of control group and were almost disconnected and the lacunae were found to be broadened. Antler and safflower-treated group showed only slight changes. The recovery rates were prominent in antler, safflower, estrogen-treated groups but they were insignificant in red ginseng and ipriflavone-treated groups.

• 한국동물위생학회지
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• 제23권3호
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• pp.247-254
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• 2000

This study was performed to elucidate the effects of antler, red ginseng, safflower seed, ipriflavone and estrogen on ovariectomized rats. The rats were fed with Ca and P deficient diet for five weeks to induce osteoporosis. After this period, these animals were fed with normal feed and treated every other day with antler(600 mg/kg, p.o), red ginseng(200 mg/kg, p.o), safflower(200 mg/kg, p.o), ipriflavone(80 mg/kg, p.o) and estrogene(400$\mu\textrm{g}$/kg, i.m) for 5 weeks. During the treatment, the rats were examined for serum concentrations of estradiol, calcitonin, Ca, p and alkaline phosphatase(ALP) activities. The results are summarized as follows 1. The levels of serum 17 $\beta$-estradiol after five weeks of treatment were showed 39.6$\pm$3.0 pg/ml by antler, 33.2$\pm$2.5pg/ml by red ginseng, 34.9$\pm$2.4pg/ml by safflower, 28.1$\pm$3.1 pg/ml by ipriflavone and 40.6$\pm$3.0pg/ml by estrogen-treated group. They were lower than 50.8$\pm$3.1pg/ml of normal control group which had not received ovariectomy. They, however, were significantly higher than 26.8$\pm$1.8pg/ml of ovariectomized non-treatment group(p<0.05). 2. The levels of serum calcitonin after five weeks of treatment were showed 0.60$\pm$0.02 ng/ml by antler, 0.55$\pm$0.04ng/ml by red ginseng, 0.59$\pm$0.02ng/ml by safflower, 0.56$\pm$0.04ng/ml by ipriflavone and 0.62$\pm$0.02ng/ml by estrogen-treated group. They were lower than 0.67$\pm$0.03pg/ml of normal control group. However, they were significantly higher than 0.45$\pm$0.05ng/ml of ovariectomized non-treatment group(p<0.05). 3. The levels of serum Ca of the rats after five weeks of treatment with antler, red ginseng, safflower, ipriflavone and estrogen were 23.51$\pm$2.19$\mu\textrm{g}$/$m\ell$, 25.22$\pm$3.44$\mu\textrm{g}$/$m\ell$, 23.20$\pm$0.02$\mu\textrm{g}$/$m\ell$, 24.76$\pm$3.57$\mu\textrm{g}$/$m\ell$, 23.07$\pm$3.66$\mu\textrm{g}$/$m\ell$, respectively. They were a bit higher than 21.43$\pm$2.22$\mu\textrm{g}$/$m\ell$ of normal control group. And non-treatment group showed 26.12$\pm$0.29$\mu\textrm{g}$/$m\ell$ which was significantly higher than that of control group(P<0.05). 4. The serum P concentraions after five weeks of treatment were showed 12.11$\pm$2.14$\mu\textrm{g}$/$m\ell$ by antler, 13.18$\pm$1.64u91m4 by red ginseng, 12.67 $\pm$2.31$\mu\textrm{g}$/$m\ell$ by safflower, 12.38$\pm$2.07$\mu\textrm{g}$/$m\ell$ by ipriflavone, 11.86$\pm$1.93$\mu\textrm{g}$/$m\ell$ by estrogen-treated group. They were a bit higher than 11.29$\pm$1.23$\mu\textrm{g}$/$m\ell$ of normal control group. And non-treatment group showed 13.42$\pm$1.87$\mu\textrm{g}$/$m\ell$ which was higher than that of control group but not significant. 5. The levels of serum ALP after five weeks of treatment were showed 164.8$\pm$3.8IU/ml by antler, 277.7$\pm$4.8IU/ml by red ginseng, 288.5$\pm$4.5IU/ml by safflower, 214.7$\pm$5.7IU/ml by ipriflavone and 159.4$\pm$5.4IU/ml by estrogen-treated group. They were significantly higher than 144.1$\pm$3.5IU/ml of normal control group(p<0.05). However, they were significantly lower than 336.9 $\pm$12.7IU/ml of ovariectomized non-treatment group(p<0.05). Antler and safflower elevated serum estradiol and calcitonin, and decreased serum ALP significantly. Therefore they were thought to have therapeutic effect on osteoposis by making inhibitory effect on osteoclasts rather than activating osteoblasts.

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 2005년도 제45회 종합학술대회 연제초록
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• pp.180-180
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• 2005

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.98.2-98.2
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• 2000