• Journal of Pharmaceutical Investigation
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• v.32 no.3
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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.

• The korean journal of orthodontics
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• v.35 no.4 s.111
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• pp.275-285
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• 2005

Ipriflavone (isoprofoxyisoflavone), a synthetic derivative from soy isoflavone diazein, has been shown to inhibit bone resorption and perhaps stimulate bone formation This study was performed to examine the effects of ipriflavone on the proliferation and bone remodeling in rat calvarial cells in vitro The rat calvarial cells were isolated from fetus aged 20 to 21 days and cultured In BGJb media The graded concentration of ipriflavone $(10^{-9}\;10^{-5}M)$ was administered into cultured cells. When the cell proliferation was estimated through the measurement of MTT assay, there was no increase in cellular proliferation of the rat calvarial cell at any ipriflavone concentration. The cellular activity was evaluated through the formation of mineralized nodules stained by alizarin red. The formation of mineralized nodules significantly increased at concentrations of $10^{-8}M,\;10^{-7}M\;and\;10^{-6}M$ ipriflavone. Reverse transcription-polymerase chain reaction analyses (RT-PCR) were done at 7 and 14 days after culture to detect the expression of Bone Sialoprotein (BSP), Type I Collagen (COL I) and Osteocalcin(OCN) As a result, the expressions of BSP and COL I increased on the 7th day of culture and the expression of OCN increased on the 14th day of culture. These results indicate that ipriflavone facilitates the bone remodeling process bvy promoting rat calvarial cell differentiation aid stimulating mineralization through increased expression of extracellular matrix genes. such as BSP. COL I and OCN.

• The korean journal of orthodontics
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• v.38 no.5
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• pp.347-357
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• 2008

Objective: The purpose of this study was to examine the effect of ipriflavone on periodontal reorganization and prevention of relapse following tooth movement. Methods: Orthodontic rubber bands were inserted between the first and second maxillary molars of 27 white male rats for 3 weeks for experimental tooth movement. From one day before the removal of orthodontic rubber band, ipriflavone was administered 50 or 400 mg/kg daily in each experimental group whereas carboxymethyl cellulose solution was administered in the control group. They were sacrificed at the 5, 10, and 15th day from the day of removal of orthodontic rubber bands. The amount of relapse was evaluated by measuring the interdental space, and the extent of periodontal reorganization was compared through histological examination. Results: In case of ipriflavone administration, the amount and velocity of relapse was less and slower compared to the control group. In addition, the ipriflavone group showed more rapid periodontal reorganization compared to the control group. Conclusions: The results of the present study suggest that ipriflavone administration can be used effectively in the prevention of relapse following orthodontic tooth movement through the acceleration of periodontal reorganization.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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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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• v.27 no.4
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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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• v.19 no.4
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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.

• Korean Journal of Veterinary Service
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• v.23 no.3
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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.

• Korean Journal of Veterinary Service
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• v.23 no.3
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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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• 2005.11a
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• pp.180-180
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• 2005

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.98.2-98.2
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• 2000