• 제목/요약/키워드: new drugs

검색결과 968건 처리시간 0.031초

Pooled Analysis of Pomalidomide for Treating Patients with Multiple Myeloma

  • Sun, Jia-Jia;Zhang, Chi;Zhou, Jun;Yang, Hui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3163-3166
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    • 2015
  • Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is a new immunomodulatory drug with high in vitro potency. Immunomodulatory drugs are hypothesized to act through multiple mechanisms. Here we performed a systemic analysis to evaluate pomalidomide-based chemotherapy (pomalidomide in combination with low-dose dexamethasone) as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the efffectiveness of pomalidomide based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: For pomalidomide based regimens, 4 clinical studies which including 291 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 41.2% (120/291). Major adverse effects were hematologic toxicity, including grade 1 or 2 anemia, leucopenia and thrombocytopenia with pomalidomide based treatment. No treatment related death occurred. Conclusion: This pooled analysis suggests that pomalidomide in combination with low-dose dexamethasone is active with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Glial Mechanisms of Neuropathic Pain and Emerging Interventions

  • Jo, Daehyun;Chapman, C. Richard;Light, Alan R.
    • The Korean Journal of Pain
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    • 제22권1호
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    • pp.1-15
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    • 2009
  • Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

당뇨병-고지혈증 모델동물의 개발 (Development of Animal Model for Diabetes and Hyperlipidemia)

  • 오승현;노경진;박인선;민본홍;두호경;안세영;김용석;성제경
    • Environmental Analysis Health and Toxicology
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    • 제19권3호
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    • pp.287-294
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    • 2004
  • Diabetic complication is one of major risk factors leading to vascular disease such as atherosclerosis, stroke, coronary heart disease and etc. Several factors affecting the acceleration of diabetic vascular complication have been known such as hypertension, hyperlipidemia, immune complex and genetic factors. To screen and develop new therapeutics agents for diabetic vascular complication, it is strongly needed to develop animal models for diabetic complications. However in rodents models, diabetic complications is not well developed. Furthermore to assess the possibility of new therapeutics for diabetic vascular complications, diabetic animal models which have the risk factors of diabetic complications is needed. We aim to develop and establish an diabetic animal model which have diabetic complications with hyperlipidemia which is one of risk factors for diabetic complications. We induced insulin -dependent diabetes by intra. venous injection of streptozotocin (35 mg/kg/day) in RICO rats which is a spontaneous animal model for hyperlipidemia. Our models (STZ RICO) showed hyperglycemia, persistent high level of plasma cholesterol and triglyceridemia with severe diabetic renal changes until 28 weeks after induction of diabetes. STZ-RICO rats could be used for the evaluations of newly developed diabetic drugs.

Potential drug targets in the GPCR-$G{\alpha}_{12}/G{\alpha}_{13}$ signaling pathways

  • Kim, Sang-Geon
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2008년도 Proceedings of the Convention
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    • pp.89-99
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    • 2008
  • GPCRs are large families of cell surface receptors that transmit signals through conformational changes upon ligand activation and an interaction with the heterotrimeric G-proteins. GPCRs regulate the cell-signaling pathways and participate in the regulation of physiological processes through the G-proteins defined by their ${\alpha}$ subunits. A family of 20 G protein-coupled receptors (GPCRs) that provide a large class of tractable drug targets for new anti-inflammatory drugs and, in certain instances, for the treatment of the inflammatory indications such as atherosclerosis, rhinitis, asthma, pulmonary disease and arthritis. In view of the important findings showing that $G{\alpha}_{12}/G{\alpha}_{13}$ regulate the various cellular processes such as actin-stress fiber formation, neurite retraction, platelet aggregation, gene induction, and apoptosis, we became interested in whether, after coupling to the activated GPCRs, the G-proteins and their downstream molecules might be involved in the pathologic processes of chronic inflammatory diseases (e.g., liver fibrosis). In this symposium, the possible link of the G-proteins with the pathophysiology will be discussed with the aim of finding potential new drug targets.

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Poly(trimethylene carbonate-co-caprolactone): An emerging drug delivery nanosystem in pharmaceutics

  • Hossain, Md. Sanower;Mohamed, Farahidah;Shafri, Mohd Affendi Mohd
    • Biomaterials and Biomechanics in Bioengineering
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    • 제5권1호
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    • pp.65-86
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    • 2020
  • As conventional drug delivery system is being improved rapidly by target-based drug delivery system, finding suitable Drug Delivery System (DDS) for new drugs remains a challenge. Although there are many drug delivery vehicles in existence, a significant improvement is required to some DDS such as for local, implant-based treatments used for musculoskeletal infections. Many polymers have been considered for providing the improvement in DDS. Synthetic polymer, for example, has gained popularity for broad-spectrum physicochemical and mechanical properties. This article reviews the biomedical applications of Poly(TriMethylene Carbonate-co-Caprolactone) (PTMCC), which has attracted attention due to its biocompatibility, biodegradability and rubber-like properties. Its synthesis, physical properties, and degradation are also discussed here. Although it is relatively new in biomedical applications, it is readily usable for the fabrication of differing format of DDS of superior mechanical strength and degradation properties. The use of PTMCC is expected to increase in coming years as more is revealed about its potentials.

의약품 리베이트의 원인과 처방에 관한 신제도론적 해석 (A Study on Rebates in the Pharmaceutical Industry from the Perspective of New Institutionalism)

  • 이하영;권용진
    • 보건행정학회지
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    • 제21권1호
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    • pp.132-157
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    • 2011
  • The purpose of this article is to examine the cause of policy non-compliance in the case of pharmaceutical rebates from the perspective of rational choice institutionalism. In Korea, there have been rebates practices between pharmaceutical companies and hospitals since the introduction of the Actual Remuneration System for insured medicine in 1999. The government has chosen the policy means of punishment to eliminate pharmaceutical rebates but the illegal practices are still widespread. Institution in rational choice institutionalism usually reflects the incentives and preferences of actors, and the Actual Remuneration System has resulted in a the lack of procedures to ensure savings on drug expenditures. Pharmaceutical rebates are the product of the institutions which reflect their incentives: the Actual Remuneration System, the current pricing policy for generic drugs, the drug distribution system, and so on. In the end, the problem of the rebates is the consequence of policy non-compliance as actors' rational choice because their incentives lead to opportunistic behaviors. We should therefore understand the incentive structure of policy stakeholders, which is derived from the view of new institutionalism; also, the newly designed Korean drug pricing policy reform must be compatible with the incentive structure.

한약 및 한약제제 관리와 연구개발 정책방향에 관한 연구 (Study on the Direction of Policies to Manage and Develop Herbs and their Products)

  • 신현규
    • 대한한의학회지
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    • 제21권2호
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    • pp.14-24
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    • 2000
  • Objectives : To direct methods of management and development of herbs and their derived products, and at the end of this study to inform the process of making new herbal drug regulations in Korea. Methods : This study analyzed the regulations and laws of western medicine drugs. Results : We have got some herbal prescriptions which are not in the eleven books of oriental medicine now in use but which have proved effective. We need to establish standards for permissions to produce medical products through those prescriptions. Besides, we need the special permissions to produce herbal products through prescriptions, especially those which have been used to treat incurable diseases. And, we can contribute to globalization of oriental medicine and to well situating of herb products and medicinal acupunctures if we produce them according to international standards. It is thought that herbal medicine has no side effect in the medical society in Korea. But, it is getting popular to administer herbal medicine and western medicine together. Thus, the side effects of taking both medicines at the same time should be documented. Conclusions : Herbal medicines and herbal products should be under the control over the whole process of production, circulation, and sales. Now, it is time for herbal medicine to be known to all over the world. Therefore, herbal medicine must meet and adhere to the standards set by the western society and WHO.

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1,2-디아미노프로판을 배위자로 한 백금(II) 착체의 선택적 세포독성 (Selective Cytotoxicity of New Platinum (II) Complex Containing 1,2-Diaminopropane)

  • 노영수;이경태;장성구;정지창
    • 약학회지
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    • 제42권5호
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    • pp.494-499
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    • 1998
  • As part of a drug discovery program to discover more effective platinum-based anticancer drugs, a series of platinum complexes of 1,2-bis(diphenylphosphino)ethane(1,2-diaminopro pane)platinum(II)dinitrate (KHPC-070) has been evaluated in vitro against various tumor cell lines and normal kidney cells. The structure of this new compound was determined by elemental analysis, infrared spectroscopy (IR) and $^{13}carbon$ nuclear magnetic resonance (NMR). With the use of nine tumor cell lines, KHPC-070 exhibited a comparable cytotoxic to cisplatin. The cytotoxicity of KHPC-070 in normal cells was quite less than that of cisplatin using 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and [$^3H$]-thymidine uptake tests in rabbit renal proximal tubular cells and human renal cortical cells. Based on these results, KHPC-070 is considered to have more selective cytotoxicity toward cancer cells than normal human/rabbit kidney cells.

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Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease

  • Yoon, Sang-Sun;AhnJo, Sang-Mee
    • Biomolecules & Therapeutics
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    • 제20권3호
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    • pp.245-255
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    • 2012
  • Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • 제19권4호
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.