Jang S.W.,Dong A Pharmaceutical Co. |
Kang M.J.,Dankook University
International Journal of Pharmaceutics | Year: 2014
The aim of this study was to improve the physicochemical properties and oral absorption of poorly water-soluble everolimus via preparation of a solid dispersion (SD) system using a solvent wetting (SW) technique. The physicochemical properties, drug release profile, and bioavailability of SD prepared by SW process were also compared to SD prepared by the conventional co-precipitation method. Solid state characterizations using scanning electron microscopy, particle size analysis and X-ray powder diffraction indicated that drug homogeneously dispersed and existed in an amorphous state within the intact polymeric carrier. Whereas, a film-like mass was obtained by a co-precipitation method and further pulverization step was needed for tabletization. The drug release from the SD tablet prepared by SW process at a ratio of drug to hydroxypropyl methylcellulose of 1:15 was markedly higher than the drug alone and equivalent to the marketed product (Afinitor®, Novartis Pharmaceuticals), a SD tablet prepared by co-precipitation method, archiving over 75% the drug release after 30 min. At the accelerated (40 °C/75% R.H.) and stress (80 °C) stability tests, the novel formula was more stable than drug powder and provided comparable drug stability with the commercially available product, which contains a potentially risky antioxidant, butylated hydroxyl toluene. The pharmacokinetic parameters after single oral administration in beagles showed no significant difference (P > 0.01) between the novel SD-based tablet and the marketed product. The results of this study, therefore, suggest that the novel SD system prepared by the solvent wetting process may be a promising approach for improving the physicochemical stability and oral absorption of the sirolimus derivatives. © 2014 Elsevier B.V.
Zhao C.,Chonbuk National University |
Kim S.H.,Chonbuk National University |
Lee S.W.,Sungkyunkwan University |
Jeon J.-H.,Seoul National University |
And 3 more authors.
BJU International | Year: 2011
OBJECTIVE To evaluate the impact and distribution of a single phosphodiesterase type 5 inhibitor (PDE5 I) dose (udenafil or tadalafil) in prostate tissue and plasma in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Thirty BPH patients complaining of erectile dysfunction along with moderate-to-severe lower urinary tract symptoms (LUTS) who underwent transurethral resection of the prostate (TURP) were enrolled in the present study. The patients were randomly divided into the three groups: group 1, TURP without PDE5 Is; group 2, 200 mg of udenafil given 1 h before TURP; and group 3, 20 mg of tadalafil given 1 h before TURP. We evaluated the concentrations of PDE5-I, cAMP and cGMP in prostate tissues and plasma, and calculated the prostate tissue-to-plasma (T/P) ratio. RESULTS The concentration of udenafil in prostate tissue and plasma was 2028.6 ± 360.8 ng/g and 463.7 ± 39.1 ng/mL, respectively, and the resulting T/P ratio was 4.4. The tadalafil concentration in prostate tissue and plasma was 385.7 ± 83.8 ng/g and 305.8 ± 41.1 ng/mL, respectively, and the T/P ratio was 1.3. Udenafil and tadalafil significantly increased the cAMP and cGMP levels in plasma and prostate tissues. CONCLUSIONS Udenafil and tadalafil significantly increased cAMP and cGMP levels and were more highly distributed in the prostate than plasma. The T/P ratio of udenafil was higher than tadalafil. These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and erectile dysfunction. © 2010 BJU INTERNATIONAL.
Dong A Pharmaceutical Co. | Date: 2014-02-11
The present invention relates to a pharmaceutical composition for forming a film directly on a wound to accelerate wound healing, a use for the same, a treatment method using the same, and a method for preparing the same. The film-forming composition according to the present invention forms a film directly on the wound to increase the adhesion to the wound. The formed thin hydrophilic film protects the wound surface to prevent infection of the wound surface, retains the physiologically active substance useful for wound healing on the wound surface to promote the wound healing, and allow drugs to be continuously delivered to the wound surface. Therefore, the composition according to the present invention has excellent wound healing effect and has excellent usability as it is not absorbed into clothing, bandage, etc., thus effectively replacing conventional gel or ointment formations for delivering physiologically active substances.
Lee T.H.,Dong A Pharmaceutical Co. |
Kim K.H.,Sungkyunkwan University |
Lee S.O.,Sungkyunkwan University |
Lee K.R.,Sungkyunkwan University |
And 2 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2011
Because delayed gastric emptying and impaired gastric accommodation are regarded as pathophysiological mechanisms underlying functional dyspepsia (FD), prokinetics and fundic relaxants have been suggested as a new treatment for FD. We isolated tetrahydroberberine (THB), an isoquinoline alkaloid (5,8,13,13atetrahydro-9,10-dimethoxy-6H-benzo[g]-1,3-benzodioxolo[5,6-a] quinolizine) from Corydalis tuber, and found that it has micromolar affinity for dopamine D2 (pKi = 6.08) and 5-HT1A (pK i = 5.38) receptors but moderate to no affinity for other relevant serotonin receptors (i.e., 5-HT1B, 5-HT1D, 5-HT 3, and 5-HT4; pKi < 5.00). Oral administration of THB not only resulted in significantly accelerated gastric emptying of normal rats in a bell-shaped relationship, with a maximal efficacy at a dose of 30 μg/kg, but also restored the delayed gastric emptying caused by apomorphine, which might be mediated by an antidopaminergic effect. Data from electromyography indicated enhanced motor function of the upper gastrointestinal tract by THB, which occurred through strengthening contractility and shortening the contraction interval. Furthermore, in rats stressed by repeated restraint, a significantly higher shift in the pressure-volume curve by THB (10 μg/kg, p < 0.05), which was inhibited by [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635), a 5-HT1A antagonist, and Nω-nitro-L-arginine methyl ester, a nitric-oxide synthase inhibitor but not a vasoactive intestinal peptide antagonist, was observed. Oral administration of THB resulted in a drastic increase of gastric accommodation in Beagle dogs. Area under the volume versus time curve was increased significantly by THB (30 μg/kg, p < 0.01) and comparable with that of sumatriptan (3 mg/kg), a potent fundic relaxant. Taken together, our data suggested that THB, with D2 receptor antagonist and 5-HT1A receptor agonist properties, has significant potential as a therapeutic for treatment of FD. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
Choi J.S.,Kangwon National University |
Choi S.H.,Dong A Pharmaceutical Co. |
Yoo H.S.,Kangwon National University
Journal of Materials Chemistry | Year: 2011
Two different growth factors were physically and chemically loaded into a single nanofibrous matrix to increase wound healing efficacy and to obtain bi-phasic release profiles of the loaded growth factors. Amine-functionalized block copolymers composed of PCL and PEG were synthesized and subsequently co-electrospun with a bFGF solution to prepare coaxial nanofibrous meshes. The nanofibrous meshes were chemically modified with an EGF by conjugating surface-exposed amine groups of nanofibers to carboxylate groups of EGF. The characterization of a core-encapsulated bFGF and a surface-immobilized EGF by X-ray photoelectron spectroscopy revealed distinctive peaks of nitrogen atoms, which confirm the presence of a surface-immobilized EGF on the nanofiber. The release profiles of the bFGF and the EGF clearly demonstrated binary release profiles of each protein: the bFGF showed a high initial burst in 24 h, whereas the EGF showed no negligible release in 7 days. Human primary keratinocyte and fibroblast cells cultivated on the nanofibrous meshes showed the highest cellular proliferation on mesh composed of the bFGF and the EGF. In an animal study, the wound closure rates of diabetic ulcers were significantly increased in 7 days when bFGF/EGF nanofibrous meshes were administered to dorsal wound sites. The expression levels of keratinocyte-specific markers were examined by RT-PCR, and keratin 14, 5, 1 have higher expression levels than the control groups. This outcome strongly suggests that bi-phasic release of bFGF and EGF greatly supported tissue recovery with the similar phenotypes as the original keratinized tissues. A histological examination of the recovered tissue also confirms that bFGF/EGF nanofibrous meshes increase the accumulation of both collagen and a cemented matrix of keratin. Thus, the nanofibrous matrix is a promising wound dressing material that can increase wound healing rates while reducing scar formation. © 2011 The Royal Society of Chemistry.