• 제목/요약/키워드: new drugs

검색결과 976건 처리시간 0.021초

교차계획 구간절단 생존자료의 비례위험모형을 이용한 분석 (Analysis of Interval-censored Survival Data from Crossover Trials with Proportional Hazards Model)

  • 김은영;송혜향
    • 응용통계연구
    • /
    • 제20권1호
    • /
    • pp.39-52
    • /
    • 2007
  • 협심증 치료의 신약에 대한 교차계획 임상시험(crossover clinical trials)에서 신약의 효능을 알아보는 운동테스트(treadmill exercise test) 결과는 중도절단 생존시간(censored survival times)으로 측정된다. 이 논문에서는 교차계획에서 수집된 중도절단 생존자료의 여러 가지 분석법에 대해 설명한다. 중도절단을 감안한 비모수적 방법들과 층화 Cox 비례위험모형 (stratified Cox proportional hazards model)에 근거한 분석법이 제시되었다. 한편, 교차계획의 두 시기에 걸쳐 수집된 생존시간의 차(difference)로부터 구간절단자료(interval censored data)가 생성되며 이에 근거한 분석법으로서 이 논문에서는 구간절단자료에 대한 Cox 비례위험모형 (proportional hazards model)의 가능성을 알아보며, 예제 자료로써 여러 방법들의 결과를 비교해 본다.

Pre-clinical QT Risk Assessment in Pharmaceutical Companies - Issues of Current QT Risk Assessment -

  • Takasuna, Kiyoshi; Katsuyoshi, Chiba;Manabe, Sunao
    • Biomolecules & Therapeutics
    • /
    • 제17권1호
    • /
    • pp.1-11
    • /
    • 2009
  • Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

Suppressive Actions of Astragali Radix (AR) Ethanol Extract and Isolated Astragaloside I on HCl/ethanol-Induced Gastric Lesions

  • Jeong, Jeong-Suk;Lee, Je-Hyuk;Lee, Sang-Hyup;Kang, Sam-Sik;Jeong, Choon-Sik
    • Biomolecules & Therapeutics
    • /
    • 제17권1호
    • /
    • pp.62-69
    • /
    • 2009
  • Roots of Astragalus membranaceus (A. membranaceus) (Astragali Radix, AR) has been used as a herbal medicine for gastrointestinal disorders in China, Korea, Japan, and other Asia countries. In this study we investigated the effects of the AR 70% ethanol extract and compounds isolated from AR on gastritis in rats and growth of human gastric cancer cells. AR 70% ethanol extract showed the potent acid-neutralizing capacities and partly cytotoxicity of Helicobacter pylori and human AGS gastric cancers cell. Astragaloside I and daucosterol, which were isolated from AR, significantly inhibited HCl/ethanol-induced gastric lesions. In addition, daucosterol increased the mucus content to almost the same as the positive control. The results of this study suggest that astragaloside I and daucosterol may be good candidates for the development of new drugs or neutraceuticals which can be used for the treatment or prevention of gastritis.

Gefitinib Inhibits the Growth of Toxoplasma gondii in HeLa Cells

  • Yang, Zhaoshou;Ahn, Hye-Jin;Nam, Ho-Woo
    • Parasites, Hosts and Diseases
    • /
    • 제52권4호
    • /
    • pp.439-441
    • /
    • 2014
  • Toxoplasma gondii is the causative agent of toxoplasmosis with symptoms of congenital neurological and ocular diseases and acquired lymphadenitis, retinochoroiditis, and meningoencephalitis. Small molecules which block the activity of protein kinases were tested in in vitro culture of T. gondii to find new therapeutic drugs of safer and more effective than the combined administration of pyrimethamine and sulfadoxine that sometimes provoke lethal Stevens-Johnson syndrome. Among them, Gefitinib and Crizotinib inhibited intracellular growth of T. gondii in HeLa cells by counting the number of T. gondii per parasitophorous vacuolar membrane whereas Sunitinib did not. Gefitinib inhibited the growth of T. gondii in a dose-dependent manner over $5{\mu}M$ up to the tolerable concentration of HeLa cells and halted the division of the parasite immediately from the time point of treatment. Gefitinib inhibition suggests that tyrosine kinases of EGFR family or other homologous kinases of the parasite itself may be the target to cause the block of T. gondii growth.

Hepatitis C Viral Infection in Children: Updated Review

  • El-Guindi, Mohamed A.
    • Pediatric Gastroenterology, Hepatology & Nutrition
    • /
    • 제19권2호
    • /
    • pp.83-95
    • /
    • 2016
  • Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

객혈과 공동 폐병변으로 폐결핵으로 오인된 폐흡충증 1예 (Pulmonary Paragonimiasis Misdiagnosed with Pulmonary Tuberculosis)

  • 박수은;송보경;황재연
    • Pediatric Infection and Vaccine
    • /
    • 제24권3호
    • /
    • pp.178-182
    • /
    • 2017
  • 우리나라에서 폐흡충증은 1960년대 까지만 해도 매우 흔하여 폐의 공동 병변을 일으키는 주요 감염 원인이었으나 현재는 매우 드문 감염병이 되었다. 16세 남자가 갑자기 열감, 기침, 객혈이 발생하여 가슴 X-선 영상검사를 실시하였고, 공기음영(air bubble)을 포함하고 있는 결절과 간유리 음영으로 세균학적으로 결핵균이 확인되지 않았으나 결핵으로 진단받고 항결핵제로 치료를 받았다. 항결핵제 치료 후에 더 이상 기침 등의 증상은 호소하지 않았으나 가슴 X-선 영상검사와 가슴 컴퓨터단층촬영검사에서 병변이 악화되어 비디오 흉강경 구역절제술을 실시 받았으며 조직검사에서 폐흡충란이 발견되어 폐흡충증으로 진단된 증례를 경험하여 보고하고자 한다.

한약엑스제의 확인시험법에 관한 연구 (Studies on the Identification Test of Herbal Medicines and its Preparations)

  • 김혜진;서용택;이종필;조정희;장영표
    • 생약학회지
    • /
    • 제40권2호
    • /
    • pp.155-160
    • /
    • 2009
  • The reference herbal extracts and their identification methods by Korean Pharmacopoeia IX were established based on the organic solvent extracts to detect their marker compounds. However, most of herbal medicine decoctions in the market are prepared with water as extracting solvent. As the reference herbal extracts and their identification methods are not appropriate for the practical test, new preparation of alternative reference herbal extracts and their identification test methods are essential for the correction of test methods and identification of herbal drugs. Three novel identification test methods were developed for Evodiae Fructus, Cimicifugae Rhizoma and Aurantii Fructus Immaturus. Total 10 reference herbal extracts and their identification methods were optimized for Ephedrae Herba, Schisandrae Fructus, Curcuma longae Rhizoma, Citri Unshius Pericarpium, Puerariae Radix, Corni Fructus, and Cinnamomi Cortex.

아토피피부염 치료를 위한 지식기반의 생약 데이터베이스 (Knowledge-based Herbal Database for the Treatment of Atopic Dermatitis)

  • 신지영;배현수;홍무창;신민규;김양석
    • 동의생리병리학회지
    • /
    • 제24권6호
    • /
    • pp.1129-1133
    • /
    • 2010
  • The treatment of Atopic dermatitis and its untapped herbal elements are recognized as possible solutions to incurable diseases stemming from overdosage of chemical drugs. Synthesizing clinical results from the Oriental medicine with scientific results from the field of Molecular biology is in the mainstream. The main goal of this research is, by objectifying the methodology of abstracting information into a compendium, to establish knowledge-based database on natural materials mingling every single related information from both Oriental and Western medicine. The constructed system, ATODERM, is the first database system about the medical herb for the treatment of Atopic Dermatitis which bearing the integrated information on Oriental medicine and Western medicine. The construction of this database renders new ways of treatment and prescriptions for researchers in the field of the Oriental medicine. Using the database that has been intensively accumulated, the possibility of creating the plausible cure for the disease can be anticipated.

High-performance liquid chromatographic assay and oral pharmacokinetics of new anti-HIV uracil derivatives, KR-V analogues, in rats

  • Lee, Youngmi;Heeok Shim;Seoungryong Yu;Hochul Shin;Moonkoo Chung;Jungkoo Roh
    • 한국응용약물학회:학술대회논문집
    • /
    • 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
    • /
    • pp.123-123
    • /
    • 1998
  • A number of uracil derivatives have been developed as anti-AIDS drugs having a mechanism of inhibiting cellular reverse transcriptase. A simple and rapid assay technique for recently synthesized KR-V analogues was developed using a high-performance liquid chromatography, and oral pharmacokinetics was examined for assessing their oral bioavailabilites. Plasma samples were analyzed by reversed-phase HPLC using an ODS column with an ultraviolet detection system. All the analogues were eluted within 12 min and the LOQ was 15-30 ng/$m\ell$. The extraction recoveries were higher than 85%, except KR-V1039, 1068 and 1720 having ester group. This chromatic method was well applied to the kinetic studies for KR-V analogues. Among 16 analogues tested in the present work, the 6 compounds including KR-V1123, 1122, 1784, 1783, 1736 and 1700 were found to be bioavailable for oral administration to rats.

  • PDF

F1064m: New Inhibitor of Cholesteryl Ester Transfer Protein (CETP), Isolated from Gliocladium virens F1064

  • Kwon, Byoung-Mog;Cho, Joung-Suk;Jeong, Tae-Sook;Kim, Sung-Uk;Son, Kwang-Hee;Kim, Young-Kook;Nam, Ji-Youn;Han, Kyu-Hoon;Bok, Song-Hae
    • 한국응용약물학회:학술대회논문집
    • /
    • 한국응용약물학회 1995년도 춘계학술대회
    • /
    • pp.65-65
    • /
    • 1995
  • Cholesteryl Ester Transfer Protein(CETP), a hydrophobic glycoprotein with molecular mass 74KDa, is a lipid transfer protein found in plasma which mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other lipoproteins, therefore, it might influence HDL levels. The lipoprotein profile associated with human CETP deficiency (that are two Japanese families, high HDL and low LDL) has low atherogenic potential, raising the possibility that CETP inhibitors can be used as antiatherosclerotic drugs.

  • PDF