A Novel & Tailorable Drug Delivery Device for the Treatment of Periodontitis
一本小说
基本信息
- 批准号:7537768
- 负责人:
- 金额:$ 15.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-13 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAgonistAnaerobic BacteriaAnti-Inflammatory AgentsAnti-inflammatoryAntibioticsBindingBiodegradable microsphereBiological AssayBloodCalciumCardiovascular systemCathepsin GCeriumChargeChlorhexidineChronicClinical TrialsCombined Modality TherapyCommunicable DiseasesConsentCountryCysteine ProteaseDepthDevelopmentDevicesDiabetes MellitusDiseaseDoxycyclineDrug Delivery SystemsDrug FormulationsEconomicsEffectivenessElastasesEmulsionsEncapsulatedEndopeptidasesEnvironmentEnzymesEstersFamilyGelatinase AGingivitisHealedHealthcareHourHydrolysisIn VitroIndividualIntentionIon ExchangeIonsKineticsLiquid substanceLiver diseasesLungMatrix Metalloproteinase InhibitorMatrix MetalloproteinasesMicrospheresMolecularNIH Program AnnouncementsNeutrophil CollagenaseNucleotidesNumbersNutrientOilsOralOral AdministrationOral cavityOsteoclastsPGLAPSSO3Pancreatic ElastasePatientsPeptide AntibioticsPeptide HydrolasesPeptide antibodiesPeptidesPerformancePeriodontal DiseasesPeriodontal PocketPeriodontitisPharmaceutical PreparationsPhysiologicalPlayPolymersPorosityPorphyromonas gingivalisPotassiumPremature BirthProceduresPropertyProtease InhibitorPublic HealthRateReactive Oxygen SpeciesRoleSaltsScienceSerine ProteaseSiteSodium ChlorideSourceSystemSystemic diseaseTNF-alpha converting enzymeTechniquesTestingTherapeuticTherapeutic AgentsTissuesTooth DiseasesTooth structureTreatment ProtocolsUnited States Food and Drug AdministrationVertebral columnVirulenceWaterWorkantimicrobialarginyllysinebasebiomaterial compatibilitybone losscathepsin Kcontrolled releasecostcost effectivedaydesignfallshealinghyperkalemiainnovationneutrophilnovelpathogenreceptorscaling and root planingsmall moleculesocial
项目摘要
DESCRIPTION (provided by applicant): This application is directed toward the development of a therapeutic drug conjugates with the intention of providing a cost effective adjunct to scaling and root planing procedures for the reduction of pocket depth in patients with adult periodontitis. This proposed study falls under an existing program announcement (PA-06-085) focusing on the "development of novel delivery systems for rapid and/or sustained, on-demand release of therapeutic agents (e.g., antimicrobial, anti-inflammatory, antibodies, peptides, nucleotides, small molecule receptor agonists/antagonists) in the oral cavity". To this end, the objective of this application will be to formulate and test the ability of several novel derivatives of an existing therapeutic agent that has proven to be effective against neutrophil-derived proteases in early testing, against several known periodontal pathogens and proteases. The major Specific Aims of this work are: 1) to test the effectiveness of the formulations to inhibit facultative anaerobes associated with periodontal disease and 2) to test their effectiveness in inhibiting the activities of bacterial and host-derived proteases that are believed to play major roles in this disease. This innovative and rational design resulted from the idea that addressing multiple biomolecular targets within the periodontal pocket environment should result in a more favorable environment for healing. Thus, the development of a biodegradable, cost-effective microsphere-based treatment for periodontitis that modulates an array of proteases and addresses bacterial burden is the subject of a clinical investigation. Public Health Significance: Periodontal disease is the most common chronic infectious disease in the world. In the U.S., a country known for good oral healthcare, more than 50 percent of adults have gingivitis and 35 percent have periodontitis. Dental disease has both a significant social and economic impact in the U.S. and is estimated to cause 189 million missed hours of work each year and expenses attributed to the disease of more than $60 billion. When the growing evidence that tooth and periodontal disease contributes to other costly systemic diseases such as cardiovascular, pulmonary, digestive and liver diseases, and preterm births, and diabetes are considered, the costs are significantly higher.
描述(由申请人提供):此申请是针对治疗性药物缀合物的开发,目的是为成人牙周炎患者的口袋深度提供成本效益的缩放和根平行程序的辅助功能。这项拟议的研究属于现有的计划公告(PA-06-085),重点是“开发新型输送系统,用于快速和/或持续的,按需释放治疗剂(例如,抗菌,抗炎性,抗体,抗体,抗体,抗体,肽,肽,核苷酸,小分子受体受体/替代的为或抗体蛋白剂)为此,本应用的目的是制定和测试现有治疗剂的几种新型衍生物的能力,这些新型治疗剂在早期测试中已被证明对中性粒细胞衍生的蛋白酶有效,以针对几种已知的牙周病原体和蛋白酶。这项工作的主要具体目的是:1)测试配方抑制与牙周疾病相关的兼性厌氧的有效性,以及2)测试其在抑制细菌和宿主衍生的蛋白酶活性中的有效性,这些蛋白酶被认为在这种疾病中起主要作用。这种创新和理性的设计是源于这样的想法,即在牙周口袋环境中解决多个生物分子靶标应该会带来更有利的康复环境。因此,开发基于可生物降解的,具有成本效益的微球治疗牙周炎,该治疗可调节一系列蛋白酶并解决细菌负担,这是临床研究的主题。公共卫生意义:牙周疾病是世界上最常见的慢性传染病。在美国,一个以良好的口腔保健而闻名的国家,超过50%的成年人患有牙龈炎,35%的人患有牙周炎。牙齿疾病在美国既有社会和经济的重大影响,估计每年造成1.89亿个缺席工作时间,归因于超过600亿美元的疾病。当越来越多的证据表明牙齿和牙周疾病会导致其他昂贵的全身性疾病,例如心血管,肺部,消化和肝病,以及早产出生,以及糖尿病,成本却大大提高。
项目成果
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