• Title/Summary/Keyword: oral delivery system

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Improvement of Bioavailability for Lovastatin using Self-microemulsifying Drug Delivery System (미세유화약물송달시스템을 이용한 로바스타틴의 생체이용률 향상)

  • Yoon, Bok-Young;Kang, Bok-Ki;Jeung, Sang-Young;Lee, Young-Won;Lee, Si-Beum;Hwang, Sung-Joo;Yuk, Soon-Hong;Khang, Gil-Son;Lee, Hai-Bang;Cho, Sun-Hang
    • Journal of Pharmaceutical Investigation
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    • v.32 no.4
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    • pp.267-275
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    • 2002
  • A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.

Characterization of alginate/carboxymethyl scleroglucan hydrogels as a delivery system for protein drug

  • Lee, Chang-Moon;Park, Jeong-Eun;Kim, Dong-Woon;Rhee, Joon-Haeng;Kim, Gwang-Yun;Lee, Ki-Young
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.580-583
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    • 2005
  • The aim of this study was to prepare a hydrogels composed of alginate blended with a carboxymethyl scleroglucan (CMSC) and evaluate the feasibility of the hydrogels as a drug delivery system for a protein. The main advantage of the alginate/CMSC hydrogels is to improve a restricted drug release from alginate hydrogels. The CMSC was chemically synthesized with chloroacetic acid and confirmed using a FT-IR. The alginate/CMSC hydrogels were prepared at distinct compositions by crosslinking with calcium ions. The swelling ratios of these hydrogels increased significantly with increasing the content of CMSC. At pH 7.4, the swelling ratios of the hydrogels increased remarkably as compared to those at pH 1.2. In ovalbumin (OVA) release test, the amount of OVA released from the hydrogels showed higher as compared to those released at pH 1.2. In addition, the release of OVA was improved with increasing the content of CMSC. Thus, the alginate/CMSC hydrogels may be used as a potential system for oral delivery of protein drugs.

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Improvement of Solubility of Atorvastatin Calcium Using Self-Microemulsion Drug Delivery System(SMEDDS) (자가미세유화를 통한 아토르바스타틴 칼슘의 난용성 개선)

  • Lee, Jun-Hee;Choi, Myoung-Kyu;Kim, Yun-Tae;Kim, Myoung-Jin;Oh, Jae-Min;Park, Jung-Soo;Mo, Jong-Hyun;Kim, Moon-Suk;Khang, Gil-Son;Lee, Hai-Bang
    • Journal of Pharmaceutical Investigation
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    • v.37 no.6
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    • pp.339-347
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    • 2007
  • SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

Preparation of Mucoadhesive Chitosan-Poly(Acrylic acid) Microspheres by Interpolymer Complexation and Solvent Evaporation Method II

  • Cho, Sang-Min;Choi, Hoo-Kyun
    • Archives of Pharmacal Research
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    • v.28 no.5
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    • pp.612-618
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    • 2005
  • A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric resid ence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

Inducing apoptosis by the inhibition of c-myb in oral squamous carcinoma cell line, KB cell

  • Lee, Jung-Chang;Moon, Hyun-Ju;Lee, Young-Hee;Jung, Ji-Eun;Sharma, Manju;Jhee, Eun-Jung;Yi, Ho-Keun
    • International Journal of Oral Biology
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    • v.32 no.4
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    • pp.127-133
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    • 2007
  • Oral squamous cell carcinoma (OSCC) is the most common malignancy and is a major cause of worldwide cancer mortality. The proto-oncogene c-myb plays an important role in regulation of cell growth and differentiation, and it is expressed at high levels in hematopoietic cells and many other types of cancers. However, the function of c-myb is not well known in OSCC. The present study aimed to reveal the function of c-myb and to test the alternation of cell growth and signaling by c-myb in OSCC. In this study, c-myb and dominant-negatibe myb(DNmyb) were expressed in an adenovirus-mediated gene delivery system to KB cells. The over-expressed c-myb brought increased cellular proliferation compared with control cells. However, DN-myb infected KB cells showed significant reduction of cell growth and enhanced induction of apoptosis to activate PARP and caspase 9. c-myb induced increase of IGF-I, -II and IGF-IR expressions while DN-myb down-regulated these expression. Activation of ERK and Akt/PKB pathway was shown only in c-myb transduced cells. These findings suggest that the role of c-myb in cell growth of oral cancer cells is partially mediated through the modulation of IGFs, ERK and Akt/PKB. From this results, DN-myb is strongly recommended as a curable gene for the treatment of c-myb dependent malignancies such as OSCC.

Expression of Cholera Toxin B Subunit and Assembly as Functional Oligomers in Silkworm

  • Gong, Zhao-Hui;Jin, Hui-Qing;Jin, Yong-Feng;Zhang, Yao-Zhou
    • BMB Reports
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    • v.38 no.6
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    • pp.717-724
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    • 2005
  • The nontoxic B subunit of cholera toxin (CTB) can significantly increase the ability of proteins to induce immunological tolerance after oral administration, when it was conjugated to various proteins. Recombinant CTB offers great potential for treatment of autoimmune disease. Here we firstly investigated the feasibility of silkworm baculovirus expression vector system for the cost-effective production of CTB under the control of a strong polyhedrin promoter. Higher expression was achieved via introducing the partial non-coding and coding sequences (ATAAAT and ATGCCGAAT) of polyhedrin to the 5' end of the native CTB gene, with the maximal accumulation being approximately 54.4 mg/L of hemolymph. The silkworm bioreactor produced this protein vaccine as the glycoslated pentameric form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB. Further studies revealed that mixing with silkworm-derived CTB increases the tolerogenic potential of insulin. In the nonconjugated form, an insulin : CTB ratio of 100 : 1 was optimal for the prominent reduction in pancreatic islet inflammation. The data presented here demonstrate that the silkworm bioreactor is an ideal production and delivery system for an oral protein vaccine designed to develop immunological tolerance against autoimmune diabetes and CTB functions as an effective mucosal adjuvant for oral tolerance induction.

The Application of Customer Relationship Management for the Effective Prenatal Care (효과적인 산전관리를 위한 고객관계관리(CRM)의 도입)

  • Shin, Sook;Paik, Soo-Kyung;Kang, Sung-Hong;Kim, Yu-Mi
    • Korea Journal of Hospital Management
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    • v.10 no.1
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    • pp.93-114
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    • 2005
  • The prenatal care is the preventive medical service to help the pregnant mother deliver the healthy baby. It's regular examines give some chances to check-up the healthy conditions. This thesis concentrates on the CRM system to support an effective prenatal care system and prove the effectiveness of it. As CRM is the adapted management related to the customer's own information, it is important to develop the CRM model classified by the patients characteristics. A general hospital in Busan operated the CRM system to carry out the effective prenatal care and there is an analysis to ensure the effectiveness of CRM system for the pregnant women in our maternity ward. The results can be summarized as follows: 1) According to the comparisons with the CRM system, we can conclude the system is desirable. (1) Maternal Age : In the age distribution, the prenatal visit frequency, triple marker freqency, oral GTT and targeted ultrasonography in the experimental group in 30 to 34 years old is higher on the whole. For over 35 years old group, the higher frequency comes out in the oral GTT and targeted ultrasonography and for 25 to 29 years old group the different figure shows just in the targeted ultrasonography. (2) Area of residence: There is a clear difference in all the items in Busan and near area but no sign of difference in prenatal visits and oral GTT in other residencial area. Especially in the targeted ultrasonography the higher figure shows in the experimental group located in the both areas. The targeted ultrasonography is known as the specific examination which should be examined by the specialists, on the contrary the other examinations can be operated in the small clinic. So the public information and seminars related with ultrasonography increases the check-up frequency. The clinic requests some ultrasonographical examinations to the specialists in general hospital. (3) Parity: The clear difference shows that the CRM system causes the prenatal visit frequency to become higher in experimental group. The figure is 9.7 times and 8.6 times each. This is opposite that the past study said multiparity reduced the average prenatal visits. But the result of CRM is considered as the method to help the multiparity understand the importance of the prenatal care. (4) Obstetrical history: In the experimental group of the spontaneous delivery group, the figure is higher in the prenatal visit frequency, triple marker, oral GTT and targeted ultrasonography but the Caesarean section delivery group has higher figure in targeted ultrasonography. (5) In the first check-up, the rate of targeted ultrasonography in under 16 week pregnancy, in the 16 week pregnancy to 32 week pregnancy and the over 32 week pregnancy in the experimental group is upper than the compared one. For the oral GTT, there is a difference in under 16 week pregnancy but no difference in prenatal visits and triple marker. 2) The analysis of characteristics of prenatal care through the decision tree resulted in the fact that the most important variable is the residential area. After the delivery frequency is following, the obstetrical history and maternal age are in order. It is the same result in the triple marker and oral GTT. Consequently it is the same order of important variables in CRM system. The effectiveness of CRM system is proved in this study. The CRM system is a marketing method to control and lead the customers through the segmentation of customer data. It increases the new customer aquisition, maintenance of loyal customers, augmentation of customers value, activation of potential customers and creation of life time customers. So eventually it can enlarge the customers value. The medical institution should make efforts to establish the data base enforced by the customer's information on the underlying ordinary data system to carry out the CRM system effectively. In addition, it should develop the a variety of marketing strategy in order to set up one to one marketing satisfying the needs of individual patients.

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Development of adjuvant for effective oral vaccine application (경구백신의 효율적인 적용을 위한 면역 보조제 개발)

  • Kim, Sae-Hae;Seo, Ki-Weon;Kim, Ju;Jang, Yong-Suk
    • Journal of Plant Biotechnology
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    • v.37 no.3
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    • pp.283-291
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    • 2010
  • Vaccine is one of the best known and most successful applications of immunological theory to human health and it protects human life through inducing the immune response in systemic compartment. However, when we consider the fact that mucosal epithelium is exposed to diverse foreign materials including viruses, bacteria, and food antigens and protects body from entry of unwanted materials using layer of tightly joined epithelial cells, establishing the immunological barrier on the lining of mucosal surfaces is believed to be an effective strategy to protect body from unwanted antigens. Unfortunately, however, oral mucosal site, which is considered as the best target to induce mucosal immune response due to application convenience, is prone to induce immune tolerance rather than immune stimulation. Since intestinal epithelium is tightly organized, a prerequisite for successful mucosal vaccination is delivery of antigen to mucosal immune induction site including a complex system of highly specialized cells such as M cells. Consequently, development of efficient mucosal adjuvant capable of introducing antigens to mucosal immune induction site and overcome oral tolerance is an important subject in oral vaccine development. In this review, various approaches on the development of oral mucosal adjuvants being suggested for effective oral mucosal immune induction.

Predictors of the Utilization of Oral Health Services by Children of Low-income Families in the United States: Beliefs, Cost, or Provider?

  • Kim Young Ok Rhee;Telleen Sharon
    • Journal of Korean Academy of Nursing
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    • v.34 no.8
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    • pp.1460-1467
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    • 2004
  • Purpose. This study examined the predictive factors enabling access to children's oral health care at the level of financial barriers, beliefs, and the provider. Methods. In-depth interviews were conducted with 320 immigrant mothers of low-income families regarding their use of oral health services for children aged four to eight years old. Access to oral health care was measured with frequency of planned dental visits, continuity of care, and age at first visit to dentist. Results. The mother took her child to the dentist at a younger age if she received referrals to a dentist from pediatrician. Regular dental visits were significantly related to household income, provider availability on week-ends, and insurance coverage. The extended clinic hours in the evenings, and the belief in the importance of the child's regular dentist visits increased the likelihood of continuing care. The mothers perceiving a cost burden for the child's dental care were also less likely to return to the dentist. Conclusion. The available care delivery system, coordinated medical care, and health beliefs were among important predictors of the health service use. The study findings suggest need for culturally competent dental health interventions to enhance access to oral health care among particularly vulnerable populations such as low-income children in Korean communities.

Methods on improvements of the poor oral bioavailability of ginsenosides: Pre-processing, structural modification, drug combination, and micro- or nano- delivery system

  • Qi-rui Hu;Huan Hong;Zhi-hong Zhang;Hua Feng;Ting Luo;Jing Li;Ze-yuan Deng;Fang Chen
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.694-705
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    • 2023
  • Panax ginseng Meyer is a traditional Chinese medicine that is widely used as tonic in Asia. The main pharmacologically active components of ginseng are the dammarane-type ginsenosides, which have been shown to have anti-cancer, anti-inflammatory, immunoregulatory, neuroprotective, and metabolic regulatory activities. Moreover, some of ginsenosides (eg, Rh2 and Rg3) have been developed into nutraceuticals. However, the utilization of ginsenosides in clinic is restrictive due to poor permeability in cells and low bioavailability in human body. Obviously, the dammarane skeleton and glycosyls of ginsenosides are responsible for these limitations. Therefore, improving the oral bioavailability of ginsenosides has become a pressing issue. Here, based on the structures of ginsenosides, we summarized the understanding of the factors affecting the oral bioavailability of ginsenosides, introduced the methods to enhance the oral bioavailability and proposed the future perspectives on improving the oral bioavailability of ginsenosides.