Preparation of Thermo-Responsive and Injectable Hydrogels Based on Hyaluronic Acid and Poly(N-isopropylacrylamide) and Their Drug Release Behaviors

Ha Dong In,Lee Sang Bong,Chong Moo Sang,Lee Young Moo,Kim So Yeon,Park Young Hoon The Polymer Society of Korea 2006 Macromolecular Research Vol.14 No.1

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30$\∼$33$^{circ}C$. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA ($M_{w}$=6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA ($M_{w}$=13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35$^{circ}C$, thus allowing the gels to maintain their shape for 24 h after in vivo administration. From the in vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

Ultrasound-Triggered Drug Release of Hydroxyapatite Coated Liposomes

조성근,위태인,하정,조선행,한건,한희동,신병철,Cho, Sung Keun,Wee, Tae In,Ha, Jeung,Cho, Sun Hang,Han, Kun,Han, Hee Dong,Shin, Byung Cheol Korean Chemical Society 2013 대한화학회지 Vol.57 No.4

리포솜은 표적 약물을 봉입하여 병소에 안전하게 전달할 수 있는 약물전달체로서 연구되고 있다. 그러나 일반적인 리포솜은 표적부위에서 약물방출이 제한적인 문제점이 있다. 따라서 본 연구에서는 리포솜의 안정성을 향상시키고 표적부위에서 외부 초음파로부터 약물의 방출을 극대화시키기 위하여 하이드록시아파타이트(hydroxyapatite, HA)가 코팅된 리포솜을 개발하였다. 대조군 리포솜은 인지질과 콜레스테롤을 이용하여 제조하였고, 대조군 리포솜의 표면에 칼슘 아세테이트, 포스포릭에시드, 그리고 25% 암모니아용액을 이용하여 HA를 코팅하였다. 모델 약물로는 독소루비신을 사용하였다. HA코팅 리포솜의 크기는 120 nm 이었고, 약물봉입효율은 95% 이상이었다. 30% 혈장용액 내에서 HA코팅 리포솜의 입자크기는 일정한 상태를 유지하였으며, 대조군 리포솜은 크기가 1.4배 증가하였다. 외부 초음파 자극에 의한 리포솜으로부터 약물 방출을 유도한 후, 방출된 약물의 세포 이입율은 HA 코팅된 리포솜이 3배 이상 대조군 리포솜에 비하여 증가하였다. 본 연구에서는 외부 초음파 자극에 의하여 리포솜으로부터 약물의 방출을 극대화시키기 위한 초음파 민감형 리포솜을 개발하였고, 본 제형은 표적부위에서 약물의 방출을 효과적으로 제어하기 위한 분야에 활용이 가능할 것이다. Liposomes, which can deliver payload at target site, have been studied as drug carrier. However, conventional liposomes have limitation for drug release at target site. Therefore, we developed hydroxyapatite (HA) coated ultrasound sensitive liposomes to increase drug release at target site and to enhance stability in blood stream. Control liposome was prepared using hydrogenated soy phosphatidylcholine (HSPC) and cholesterol, and then we assessed HA coating on the surface of control liposomes using calcium acetate, phosphoric acid, and 25% ammonium solution. Doxorubicin was used as a model drug. Size of HA coated liposomes was 120 nm and encapsulation efficiency of doxorubicin in liposomes was up to 95%. Size of HA coated liposomes are not changed in 30% serum solution, however, the control liposomes was 1.4 fold increased. After ultrasound triggered drug release from liposomes, intracellular efficiency of drug released from HA coated liposomes was 3 fold increased compared to control liposomes. In this study, we developed ultrasound sensitive liposomes to enhance drug release, which will be applied in controlled drug release at disease site.

연구논문 : 만성 바이러스간질환에서 간섬유화의 다양한 비침습 혈청표지자검사의 비교

김선민 ( Sun Min Kim ),손주현 ( Joo Hyun Sohn ),김태엽 ( Tae Yeob Kim ),노영욱 ( Young Wook Roh ),은창수 ( Chang Soo Eun ),전용철 ( Yong Cheol Jeon ),한동수 ( Dong Soo Han ),오영하 ( Young Ha Oh ) 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.4

목적: 만성 바이러스간질환에서 병의 경과와 예후를 평가하고 치료반응을 예측함에 있어 간섬유화의 진단은 중요하다. 최근 간섬유화 평가에 표준방법이지만 침습적 간생검을 대신하여 여러 가지 비침습적 진단법이 이용되고 있고, 또한 새로운 검사법들이 개발되고 있다. 저자들은 만성 B형 및 C형간염 환자를 대상으로 임상에서 광범위하게 흔히 시행하는 혈액검사와 임상 소견을 이용한 아래와 같은 진단법들만으로 간섬유화를 얼마나 정확하게 평가할 수 있는지 알아보고, 단일 검사로 간섬유화를 평가하는 데 유용하다고 알려져 있는 hyaluronic acid(HA)와 IV형 콜라겐 농도와 비교하여 그 임상적 유용성을 평가하였다. 대상과 방법: 2002년 3월부터 2007년 2월까지 만성 바이러스간 질환으로 간생검을 시행받은 225명의 환자(HBV 180명, HCV 43명, HBV+HCV 2명)를 대상으로 분석하였다. 간생검을 시행하는 날에 말초혈액검사, 혈액응고검사, 혈청생화학검사를 시행하고, 혈중 HA, IV형 콜라겐 농도를 측정하였다. 간섬유화의 정도는 F0(섬유화가 없음), F1(문맥역 섬유화), F2(문맥주변부 섬유화), F3(섬유성 격막) 및 F4(간경변증)의 4단계로 구분하였다. 대상 환자를 F0-1, F2-4 혹은 F0-2, F3-4의 두 집단으로 분류하여 두 집단을 구분하고자 할 때 AAR(AST/ALT ratio), API(age-platelet index), APRI(AST to platelet index), CDS(cirrhosis discriminant score), platelet count, HA, IV형 콜라겐의 예측능을 area under the receiver operating characteristic curve (AUROC)값을 이용하여 비교하였다. 결과: 대상환자의 섬유화의 단계는 F0 집단은 17명, F1 집단은 40명, F2 집단은 61명, F3 집단은 74명, F4 집단은 33명이었다. 의미 있는 간섬유화를 F2 이상으로 판단할 때, 의미 있는 섬유화의 예측에 대한 AUROC 값은 APRI=0.822, CDS=0.776, platelet count=0.773, API=0.756, HA=0.749, IV형 콜라겐=0.718, AAR=0.642 순이었고, F3 이상의 광범위한 섬유화 예측에 대한 AUROC값은 CDS=0.835, platelet count=0.795, API=0.794, HA=0.766, AAR=0.711, IV형 콜라겐=0.697, APRI=0.691 순으로 관찰되었다. 결론: 만성 바이러스간질환에서 간섬유화를 평가하는 데 임상 소견 및 혈액검사를 이용한 방법들이 비침습적 진단법 중 단독 검사로도 유용한 것으로 알려져 있는 혈중 HA와 IV형 콜라겐 농도와 비교하여 우월하거나 대등하였다. 특히 APRI는 다른 인자들에 비해 F2 이상의 의미 있는 섬유화를 예측하는 데 가장 유용하였고, CDS는 F3 이상의 광범위한 섬유화를 예측하는 데 가장 유용하였다. Background/Aims: The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. Methods: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. Results: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (≥F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (≥F3). Conclusions: Conclusions: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis. (Korean J Hepatol 2009;15:454-463)

Effect of Non-animal-Derived Nitrogen Sources on the Production of Hyaluronic Acid by Streptococcus sp. KL0188

Lee, Gil-Yong,Ha, Suk-Jin,Jung, Jong-Hyun,Seo, Dong-Ho,Park, Jong-Yul,Kim, Su-Rin,Park, Nam-Woo,Kweon, Dong-Keon,Park, Sang-Hoo,Park, Cheon-Seok The Korean Society for Applied Biological Chemistr 2009 Applied Biological Chemistry (Appl Biol Chem) Vol.52 No.3

Hyaluronic acid (HA) is a linear high-molecular-weight polysaccharide with useful biomedical applications. Streptococcus zooepidemicus, a typical HA-producing bacterium, requires an animal-derived nitrogen source such as tryptone, peptone or sheep blood as a nutrient. Sixteen non-animal-derived (NAD) nitrogen sources were tested as a replacement for the expensive animal-derived nitrogen sources, which may have safety issues. Among the sixteen tested NAD nitrogen sources, a yeast-derived nitrogen source (YE 0251) showed the highest HA productivity, which was equivalent to the control HA production medium containing tryptone in a 5-L jar and in 3,000-L industrial fermentations. In the 3,000-L fermentation, YE 0251 increased cell mass (dry cell weight) and HA production by 11% and 8%, respectively, compared with the control HA production medium. The fmal specific volumetric productivity (0.41 g/L h) was improved by about 70% after reducing the fermentation time from 20 h to 12 h, compared to the conventional production medium.

혈우병 소견을 가진 뇌출혈 환자 치험(治驗) 1례(例)

정인태,서병관,이현종,하지영,강미경,홍장무,백용현,박동석,최도영,Jung, In-tae,Seo, Byung-kwan,Lee, Hyun-jong,Ha, Ji-young,Kang, Mi-kyeong,Hong, Jang-moo,Baek, Yong-hyeon,Park, Dong-suk,Choi, Do-young 대한침구의학회 2003 대한침구의학회지 Vol.20 No.4

Objective : Hemophilia, a genetically determined disorder, is characterized by abnormality of the coagulation mechanism due to functional deficiency of a specific factor, namely VIII or IX. In this study, the effect of Dong-Si acupuncture therapy on the cerebral hemorrhage patient with hemophilia was evaluated. Methods : We treated him with acupuncture by stimulating Dong-Si acupuncture point(Yuk Wan) and assessed the effect by using manual dynamic evaluation of MRC(Medical Research Council) and Modified Barthel Index. Results : After treatment, the bleeding tendency was grossly reduced and bleeding lesion was absorbed gradually. And manual dynamic evaluation of the upper extremity increased from 4 grade to 5 grade. Conclusions : This result suggest that Dong-Si acupuncture therapy on the cerebral hemorrhage patient with hemophilia was effective. And futher studies are required to concretely prove the effectiveness of Dong-Si acupuncture therapy for treating hemorrhagic diseases.

Current Status of Ginseng Cultivation and Soil Characteristics of Northeastern Three Provinces in China

Park, Yang Ho,Kim, Jang Uk,Kim, Dong Hwi,Sonn, Yeon Kyu,Yun, Jin Ha,Moon, Huhn Pal,Cho, Soo Yeon 한국토양비료학회 2016 한국토양비료학회지 Vol.49 No.6

This study was conducted to improve the continuous techniques for international competitiveness of ginseng industry to Korea-China FTA negotiation and conclusion, and provide the basic information for ginseng industry development of Korea. It was carried out the visiting of the northeastern three provinces (Jilin, Liaoling and Heilongjang) in China for 3-year from 2014 to 2016 and observed the farmers' fields of ginseng cultivation with soil environmental status. The types of ginseng cultivation could be observed in small scales of 0.5~3.0 ha, in middle scales of 4.0~10.0 ha and in large scales of 30~700 ha with the kinds of imhasam, Chinese ginseng, Korean ginseng and western ginseng. Also ginseng was cultivated in newly reclaimed land of forest in two types of direct seeding and transplanting of ginseng seedlings. The field beds of ginseng growing were covered with vinyl films in arch design of 100~130 cm height and vinyl was painted in spraying with blue, green and yellow colours for shading. It was investigated in status of the physico-chemical properties of soils. The physical information on the field soils were silt loam, loam and sandy loam in soil textures, and some plain in low slope, some alluvial fan or local valley in forest of land topography. Soil pH ranged within 5.0~5.2, soil EC was $0.93{\sim}3.78dS\;m^{-1}$, organic matter was $37{\sim}35g\;kg^{-1}$, nitrate nitrogen $63{\sim}490mg\;kg^{-1}$, available $P_2O_5$ $55{\sim}163mg\;kg^{-1}$, and in exchangeable cations, K was 0.30~0.98, Ca was 6.5~14.0, Mg was $1.1{\sim}5.3cmol_c\;kg^{-1}$ in ranges. Farmers used the fertilizer for ginseng cultivation in 10~11 t of compost, $200{\sim}400kg\;ha^{-1}$ of complex fertilizer and $750kg\;ha^{-1}$ of oil cakes. The northeastern three provinces of China can use the newly lands with large areas of ginseng cultivation in soil sickness by continuous cropping. and the soil basic fertility is batter than that of Korean in standard guide of ginseng cultivation soil.

Current Status of Ginseng Cultivation and Soil Characteristics of Northeastern Three Provinces in China

Yang Ho Park,Jang Uk Kim,Dong Hwi Kim,Yeon Kyu Sonn,Jin Ha Yun,Huhn Pal Moon,Soo Yeon Cho 한국토양비료학회 2016 한국토양비료학회지 Vol.49 No.6

This study was conducted to improve the continuous techniques for international competitiveness of ginseng industry to Korea-China FTA negotiation and conclusion, and provide the basic information for ginseng industry development of Korea. It was carried out the visiting of the northeastern three provinces (Jilin, Liaoling and Heilongjang) in China for 3-year from 2014 to 2016 and observed the farmers’ fields of ginseng cultivation with soil environmental status. The types of ginseng cultivation could be observed in small scales of 0.5∼3.0 ha, in middle scales of 4.0∼10.0 ha and in large scales of 30∼700 ha with the kinds of imhasam, Chinese ginseng, Korean ginseng and western ginseng. Also ginseng was cultivated in newly reclaimed land of forest in two types of direct seeding and transplanting of ginseng seedlings. The field beds of ginseng growing were covered with vinyl films in arch design of 100∼130 cm height and vinyl was painted in spraying with blue, green and yellow colours for shading. It was investigated in status of the physico-chemical properties of soils. The physical information on the field soils were silt loam, loam and sandy loam in soil textures, and some plain in low slope, some alluvial fan or local valley in forest of land topography. Soil pH ranged within 5.0∼5.2, soil EC was 0.93∼3.78 dS m<SUP>-1</SUP>, organic matter was 37∼35 g kg<SUP>-1</SUP>, nitrate nitrogen 63∼490 mg kg<SUP>-1</SUP>, available P2O5 55∼163 mg kg-1, and in exchangeable cations, K was 0.30∼0.98, Ca was 6.5∼14.0, Mg was 1.1∼5.3 cmolc kg<SUP>-1</SUP> in ranges. Farmers used the fertilizer for ginseng cultivation in 10∼11 t of compost, 200∼400 kg ha<SUP>-</SUP>1 of complex fertilizer and 750 kg ha<SUP>-1</SUP> of oil cakes. The northeastern three provinces of China can use the newly lands with large areas of ginseng cultivation in soil sickness by continuous cropping. and the soil basic fertility is batter than that of Korean in standard guide of ginseng cultivation soil.

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

Kim, Dae Hwan,Lee, Nam,Shin, Dong Ah,Yi, Seong,Kim, Keung Nyun,Ha, Yoon The Korean Neurosurgical Society 2016 Journal of Korean neurosurgical society Vol.59 No.4

Objective : To compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome. Methods : From January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Results : We reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group). Conclusion : The fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might induce non-union after surgery with hydroxyapatite DBM.

남산의 소나무림, 신갈나무림, 아까시나무림의 낙엽생산과 토양유기탄소 동태

정헌모 ( Heon Mo Jeong ),김해란 ( Hae Ran Kim ),신동훈 ( Dong Hoon Shin ),이경미 ( Kyoung Mi Lee ),이승혁 ( Seung Hyuk Lee ),한영섭 ( Young Sub Han ),장래하 ( Rae Ha Jang ),이상경 ( Sang Kyeong Lee ),김태규 ( Tae Kyu Kim ),유영한 한국환경생물학회 2013 환경생물 : 환경생물학회지 Vol.31 No.2

남산의 소나무림, 신갈나무림 그리고 아까시나무림에서 2008년 1월부터 2009년 12월까지의 월별 낙엽생산량과 토양의 유기탄소량을 조사하였다. 소나무림은 2008년과 2009년 모두 10월에 낙엽생산량이 가장 많았으며, 2008년 1월과 2009년 12월에 낙엽생산량이 가장 적었다. 신갈나무림은 2008년과 2009년 모두 11월에 낙엽생산량이 가장 많았으며, 2월에 낙엽생산량이 가장 적었다. 아까시나무림은 2008년 11월과 2009년 10월에 낙엽생산량이 가장 많았으며, 2008년 1월과 2009년 12월에 낙엽생산량이 가장 적었다. 이것은 한반도 중부에서 상록성의 소나무림이 낙엽성의 참나무숲 보다 더 일찍 낙엽이 진다는 것을 의미한다. 소나무림과 신갈나무림, 아까시나무림의 2년 평균의 낙엽생산량은 7.07, 6.36, 5.02 ton ha-1로 소나무가 가장 많았다. 소나무림과 신갈나무림, 아까시나무림의 2년 평균의 토양유기탄소량은 76.2, 68.6, 72.5 ton C ha-1로 소나무림에서 가장 많았다. 이처럼 소나무숲에서 높게 나타난 것은 남산에서 신갈나무나 아까시나무를 벌목하여 임목밀도가 줄었기 때문이다. The objective of this study was to estimate dynamics of litter production and soil organic carbon of Pinus densiflora forest, Quercus mongolica forest, and Rhobina pseudo-acasia forest at Mt. Nam as a part of Korea National Long-Term Ecological Research (KNLTER) from 2008 to 2009. Litter production of P. densiflora forest was the highest in October 2008, 2009 and the lowest in January 2008 and December 2009. Litter production of Q. mongolica forest was the highest in November and the lowest in February in 2008 and 2009. Litter production of R. pseudo-acacia forest was the highest in November in 2008 and October in 2009 and the lowest in January in 2008 and December in 2009. It means that leaves of P. densiflora forest shed earlier than deciduous oak forests in Korean central region. An average of litter production for 2 years was 7.07, 6.36, 4.66 ton ha-1 in P. densiflora forest, Q. mongolica forest, R. psuedo-acacia forest, respectively. An average of soil organic carbon matter for 2 years was 88.3, 76.5, 84.2 ton ha-1 in P. densiflora forest, Q. mongolica forest, R. psuedo-acacia forest, respectively.

Trophic importance of meiofauna to polychaetes in a seagrass (Zostera marina) bed as traced by stable isotopes

Ha, Sun-Yong,Min, Won-Ki,Kim, Dong-Sung,Shin, Kyung-Hoon Cambridge University Press [etc.] 2014 Journal of the Marine Biological Association of th Vol.94 No.1

<P> Stable carbon and nitrogen isotope ratios of benthic invertebrates and their potential food sources, such as suspended particulate organic matter (POM), benthic microalgae, attached algae and seagrass, were identified in Dong-dae Bay during the winter. The carbon stable isotope ratios demonstrate that filter feeders, such as oysters (?19.5 ± 1.0‰), use benthic microalgae (?21.2 ± 0.2‰) as a major food, and polychaetes such as Glycera spp. (?14.0 ± 0.6 ‰) preferentially use meiofauna, such as nematodes (?14.0 ± 0.4‰) and copepods (?13.3 ± 1.0‰). These meiofauna may feed on mixed resources (including bacteria) with the isotope ratios between benthic microalgae (?21.2 ± 0.2‰) and seagrass (?9.3 ± 01.0‰). These findings are consistent with the trophic enrichment in the nitrogen isotope ratios (by 3?4‰) between consumers and food sources. Moreover, the results of the MixSIR model based on the observed isotope ratios suggest a large seagrass contribution to the food sources of benthic organisms such as meiofauna (~53.7?62.6%) and macrobenthos (~41.1?68%) through the food web. This model additionally suggests a relatively large contribution of benthic microalgae to the food sources of filter feeders (i.e. 26.4% for oysters). </P>