지속성 진통작용 물질인 Capsaicinoid 의 흰쥐 척수내 Substance P 함량 및 생합성에 미치는 영향

김해영,손여원,이상섭,이승기 ( Hai Young Kim,Yeo Won Sohn,Sang Sup Lee,Seung Ki Lee,Seung Ki Lee ) 생화학분자생물학회 1990 BMB Reports Vol.23 No.2

We aimed in this study to evaluate the effects of capsaicinoids on the cellular concentration of substance P(SP) and substance P-mRNA in rat spinal cord. This study was based on the fact that longlasting analgesic, capsaicin caused depletion of SP from primary afferent neurons in dorsal root ganglia. After administration of 6-paradol (80, 500, 1000 ㎎/㎏) or capsaicin (80 ㎎/㎏) in rats, the cellular concentration of SP and its mRNA in spinal cord were analyzed by radioimmunoassay and slot blot hybridization analysis respectively. 6-Paradol, like capsaicin, reduced in dose-dependent manner the content of SP in rat spinal cord. Additionaliv, SP-mRNA concentration was also reduced to 61% of the control level at 3 h after capsaicin administration and was restored to the control level after 1 day. In 6-paradol treated group, substance P-mRNA concentration was not detectably reduced at 3 hours but significantly reduced to 49% of the control level at 1 day after 6-paradol treatment. These results support for the previous notion suggesting that the action mechanism of capsaicinoid analgesia may be primarily based on the depletion of SP from primary afferent neurons. These results also suggest that capsaicinoid analgesics may play a role at the transcription level of SP synthesis in rat spinal neurons.

재조합 사람성장호르몬(소바트로핀)의 KFDA표준품(KS 98/674) 설정연구

신원(Won Shin),정지원(Jee Won Joung),진재호(Jae Ho Jin),Adrian F. Bristow,손여원(Yeo Won Sohn) 대한약학회 2001 약학회지 Vol.45 No.2

The complexity and variability of both the biologicals and the bioassays used to test them led to the use of the reference standard- a sample of the product of defined purity and potency, against which all preparations of that product must be calibrated. In order to prepare and establish KFDA reference standard for recombinant human growth hormone(somatropin), somatropin substance was filled in ampoules in National Institute for Biological Standards and Control(NIBSC). The candidate KFDA reference standard for somatropin(designated as 98/674) was evaluated to determine the suitability of serving as a KFDA reference standard for somatropin by the collaborative study, in which 10 laboratories participated. Physicochemical analysis and in vivo bioassay were performed by direct comparison with the international somatropin standard 88/624. 98/674 was identified as somatropin by SDS-PAGE, IEF, peptide mapping, and HPLC. Determination of somatropin content by SE-HPLC yielded a mean estimate of 2.01mg somatropin per ampoule. Data from the study also yielded mean values of 0.39+/-0.26% for high molecular weight impurities by SE-HPLC and mean values of 2.13 +/- 1.29 % for somatropin related proteins by RP-HPLC. Estimates of relative potency by weight gain bioassay in the hypophysectomised rats showed that relative potency of KS 98/674 was 1.07 against IS 88/624. Based on the results of the collaborative study, the candidate reference standard for somatropin is suitable to serve as a KFDA reference standard for somatropin.

지속성 진통작용 물질인 Capsaicinoids의 흰쥐 척수내 Substance P 함량 및 생합성에 미치는 영향

김해영,손여원,이상섭,이승기,Kim, Hai-Young,Sohn, Yeo-Won,Lee, Sang-Sup,Lee, Seung-Ki 생화학분자생물학회 1990 한국생화학회지 Vol.23 No.2

강력한 지속적 진통 효과를 나타내는 것으로 알려진 capsaicin은 작용기전은 밝혀져 있지 않으나 dorsal spinal cord와 dorsal root ganglia에 작용하여 신경전달물질이라 생각되는 substance P(SP)를 선택적으로 감소시키므로 지속적인 진통효과를 나타낼 것이라고 제시된 바 있다. 따라서, 본 연구에서는 capsaicin과, 그 analogue로 capsaicin과는 달리 신경 독성이 거의 없는 6-paradol이 척수내 신경조직에 존재하는 SP 농도변화에 미치는 효과 및 SP-mRNA 생합성에 미치는 영향을 분석하여, 이들 capsaicinoids의 진통 효과와 SP-생합성에 미치는 영향과의 상관관계를 규명코자 하였다. 생후 6주된 Sprague-Dawley male rat에 6-paradol(80, 500, 1000 mg/kg) 또는 capsaicin(80 mg/kg)을 ether 마취상태에서 피하주사하고 3시간, 1일, 5일 후에 척수내 SP 함량을 radioimmunoassay 방법으로 측정한 결과, 3시간부터 vehicle 투여군에 비해 capsaicin과 6-paradol 투여군에서 용량 의존적으로 유의성 있는 SP 함량 감소를 보였고, 그 효과가 5일까지도 유지되었다. 또한 이들 약물의 SP-유전자 전사활성에 미치는 영향을 분석하기 위해 slot blot hybridization 방법으로 SP-mRNA의 농도를 측정한 결과, capsaicin 투여군에서는 SP-mRNA 농도가 3시간에 유의적으로 61%로 감소하였으나 1일 후에 90%로 회복되었다. 그러나 6-paradol(1000 mg/kg) 투여군에서는 3시간에는 유의적 감소를 보이지 않았고 1일 후에 49%로 감소하였다. 본 연구 결과는 capsaicinoids 투여 후 초기의 척수내 SP 함량의 감소는 신경조직으로부터의 SP 유리에 따른 것이고, 그 다음의 지속적인 SP의 신경세포내 감소현상은 감각신경에서의 SP 생합성과정 중 SP-mRNA 합성단계에서의 억제효과 때문이라는 가설을 뒷받침하는 결과로 판단된다. We aimed in this study to evaluate the effects of capsaicinoids on the cellular concentration of substance P(SP) and substance P-mRNA in rat spinal cord. This study was based on the fact that long-lasting analgesic, capsaicin caused depletion of SP from primary afferent neurons in dorsal root ganglia. After administration of 6-paradol (80, 500, 1000 mg/kg) or capsaicin (80 mg/kg) in rats, the cellular concentration of SP and its mRNA in spinal cord were analyzed by radioimmunoassay and slot blot hybridization analysis respectively. 6-Paradol, like capsaicin, reduced in dose-dependent manner the content of SP in rat spinal cord. Additionallv, SP-mRNA concentration was also reduced to 61% of the control level at 3 h after capsaicin administration and was restored to the control level after 1 day. In 6-paradol treated group, substance P-mRNA concentration was not detectably reduced at 3 hours but significantly reduced to 49% of the control level at 1 day after 6-paradol treatment. These results support for the previous notion suggesting that the action mechanism of capsaicinoid analgesia may be primarily based on the depletion of SP from primary afferent neurons. These results also suggest that capsaicinoid analgesics may play a role at the transcription level of SP synthesis in rat spinal neurons.

Polymerase Chain Reaction을 이용한 Yersinia pestis의 조기진단법 개발

오호정(Ho-Jung Oh),손여원(Yeo-Won Sohn),전정훈(Jeong-Hoon Chun),박한오(Han-Oh Park),민홍기(Hong-Ki Min) 大韓微生物學會 1999 大韓微生物學會誌 Vol.34 No.4

Nested Polymerase Chain Reaction을 이용한 병원성 Yersinia enterocolitica와 Yersinia pseudotuberculosis의 조기진단법 개발에 관한 연구

오호정(Ho-Jung Oh),손여원(Yeo-Won Sohn),홍성화(Seung-Hwa Hong),민홍기(Hong-Ki Min) 大韓微生物學會 1999 大韓微生物學會誌 Vol.34 No.2

수두생바이러스백신 국가표준품 (2차) 제조 및 확립에 관한 연구

김연희(Yeon Hee Kim),김도근(Dokeun Kim),손여원(Yeo Won Sohn),한의리(Euiri Han),김석환(Seok Hwan Kim),임종미(Jong-Mi Lim),원윤정(Yun Jung Won),윤희성(Heui Seong Yoon),조문희(Moon Hee Jo),김관수(Kwan Soo Kim),김재욱(Jaeok Kim) 한국생물공학회 2010 KSBB Journal Vol.25 No.6

수두 생바이러스 백신과 같은 생물의약품은 다양한 물질이 복합적으로 구성되어 있어 단순한 물리·화학적 분석방법만으로는 그 특성을 규명할 수 없다. 따라서 이러한 생물의약품의 품질을 평가하기 위해서는 표준품이 필수적이다. 2002년과 2003년에 제조 및 확립한 1차 국가표준품의 재고량 소진 및 역가 감소에 따라 식품의약품안전평가원에서는 수두 생바이러스 백신의 2차 국가표준품을 확립하기 위하여 2008년 용역연구사업을 통해 국내의 수두 생바이러스 백신 제조회사에서 표준품 후보물질을 제조하였으며, 국가표준품후보물질의 역가산정을 위하여 국내 제조사 및 식품의약품안전평가원에서 공동연구를 수행하였다. 국내제조사를 포함한 3개의 공동연구 시험소에서 7회 이상의 반복시험을 수행하여 얻은 공동연구 결과를 통계학적으로 분석한 결과 3곳의 공동연구 시험소의 통합역가에 대한 변이계수 (coefficient variation, CV)는 1.24%로 각 시험소간의 기하평균 (GMT) 변동 수준이 매우 낮음을 확인할 수 있었다. 또한, 수두 생바이러스 백신의 2차 국가표준품의 표시역가는 4.26 log10 PFU/0.5 mL로 산정하였다. Biological products, such as live varicella vaccine, are composed of biological substances derived from biological organisms. It is very difficult to identify these biologics’ characteristics by analysis of simple physical and chemical methods alone. So the reference material is essential in order to evaluate the quality of bilogics. The 1’st national standard for varicella live vaccine was manufactured, established in 2002 and 2003, and have been used for the manufacturer’s quality control and national lot release since then. As the lack of its availability and the decrease of its stability, this study was initiated by National Institute of Food and Drug Safety Evaluation (NiFDS) in 2008 to manufacture and establish the 2nd national standard for varicella live vaccine. The candidate material was manufactured from one of domestic manufacterers and the joint research of the NiFDS and manufacturers of varicella live vaccine was conducted to estimate of the reliable virus content. In the collaborative study, 3 laboratories including NiFDS performed the virus content test more than 7 times and all assay results were statistically analyzed. The mean coefficient of variation (CV) was 1.24%, and the geometric mean titre (GMT) variation range of each laboratory was low. On the basis of the results of this study, the candidate material of 2nd national standard for varicella live vaccine was assigned a potency of 4.26 log10 pfu/0.5 mL, when reconstituted in 0.7 mL.

유전자재조합 인터페론 알파의 HPLC-PDA에 의한 함량분석

김지현,박지은,백승권,김춘미,홍성화,이화정,손여원,Kim, Gi-Hyun,Park, Ji-Eun,Paek, Seung-Kwan,Kim, Choon-Mi,Hong, Seung-Hwa,Lee, Hwa-Joung,Sohn, Yeo-Won 대한약학회 2009 약학회지 Vol.53 No.3

Recombinant interferon alpha-2a is an active formula for the treatment of various cancer cells like malignant melanoma and a variety of virus infection diseases like acute or chronic hepatitis. The bioassay system based on the measurement of virus inhibitory activity by interferon has been used for interferon analysis with low repeatability. Here, we developed the HPLC assay to measure reproducibly interferon alpha-2a protein content which is replaceable to the reported bioassay. This method separated interferon alpha-2a from its oxidized forms and human serum albumin used as excipients. The regression coefficient using interferon alpha-2a EP CRS is more than 0.9 in the range from 5 ${\mu}g/ml$ to 200 ${\mu}g/ml$. The recovery result in the range from 15 ${\mu}g/ml$ to 60 ${\mu}g/ml$ is $97{\sim}104%$ and the precision is $0.2{\sim}1.7%$. The interferon alpha contents of 5 products are about 30 ${\mu}g/ml$.

우황과 사향의 간세포 보호효과

최영주(Young Ju Choi),이미경(Mi Kyeong Lee),손여원(Yeo Won Sohn),이흠숙(Heum Sook Lee),김영중(Young Choong KIm),민홍기(Hong Ki Min) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.3

The antihepatotoxic activity of Bezoar Bovis and Moschus was investigated by in vitro assay method using galactosamine and carbon tetrachloride-induced cytotoxicity in primary-cultured rat hepatocytes. The antihepatotoxic activity was evaluated by measuring the level of glutamate pyruvate transaminase and sorbitol dehydrogenase which were released from the necrotic hepatocytes to the culture medium. In galactosamine-intoxicated hepatocytes, the chloroform fraction of Bezoar Bovis reduced the level of glutamate pyruvate transaminase and sorbitol dehydrogenase resulting in 65% and 59% protection, respectively. The n-Hexane fraction of Moschus resulted in 45% and 40% protection, respectively in this system. In the case of carbon tetrachloride-intoxicated rat hepatocytes, Bezoar Bovis did not have significant effect and only the aqueous fraction of Moschus showed 42% and 40% protection, respectively.

염산비퀴딜 캡슐 및 알리벤돌 정의 용출시험에 관한 연구

황정분(Joungboon Hwang),구은주(Eun Joo Koo),고서연(Seu Youn Go),조경철(Kyung Chul Cho),문현주(Hyun-Ju Moon),조수열(Soo Yeul Cho),강찬순(Chan Soon Kang),손여원(Yeo Won Shon),김영옥(Young Ok Kim),손경희(Kyung Hee Sohn),조대현(Dae Hyun 대한약학회 2010 약학회지 Vol.54 No.5

The dissolution test method and an analytical procedure by HPLC were developed and validated for viquidil hydrochloride capsules and alibendol tablets. These drugs were not yet characterized by the dissolution specifications in Korean Pharmaceutical Codex. So, with each reference and test drugs, we did the preliminary and standard experiments based on the Korean Pharmacopeia Guideline of dissolution testing for solid oral dosage forms. The dissolution test for viquidil hydrochloride capsules was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 50 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 30 min in this method. Also the dissolution test for alibendol tablets was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 100 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 45 min in this method. The dissolution samples were analyzed with a precise and accurate HPLC method. The developed dissolution test showed specificity, linearity, precision and accuracy within the acceptable range. The dissolution testing method described above was adequate for the purpose and may be proposed as a pharmacopeial standard to assess the performance of viquidil hydrochloride capsules and alibendol tablets.