Size,shape,charge and“stealthy”surface:Carrier properties affect the drug circulation time in vivo

The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time.For most drugs,sufficient in vivo circulation time is the basis of high bioavailability.Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system,to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect.The physical and chemical properties of drug carriers,such as size,shape,surface charge and surface modification,would affect their in vivo circulation time,metabolic behavior and biodistribution.The final circulation time of carriers is determined by the balance between macrophage recognitions,blood vessel penetration and urine excretion.Therefore,when designing the drug delivery system,we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually.This article mainly reviews the effect of carrier size,size,surface charge and surface properties on its circulation time in vivo,and discusses the mechanism of these properties affecting circulation time.This review has reference significance for the research of long-circulation drug delivery system.

Inhalation properties of water-soluble drug loaded liposomes atomized by nebulizer

The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems,because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.

Application of Well-Known Antiviral Drugs in the Field Formed by the Unexplained Properties of Low-Level Laser Radiation in Therapy of Covid-19 and Chronic Viral Hepatitis

Low-level laser therapy (LLLT) or cold laser has been used in medicine for several decades. However, the method utilizes a direct contact of the light beam with a patient. Further research resulted in development of another method that enables remote transmission of the pharmacological properties of a medicament into a human body with the application of low-level laser radiation as the light source. 18 patients with different viral diseases were treated with the antiviral drugs placed into the field formed by the unexplained properties of low-level laser radiation of the “device for transfer of the pharmacological properties of a drug into the patient’s body”. This resulted in improvement of the patient’s condition, the absence of side effects and adverse reactions when using drugs in the proposed device and shortened therapy period for patients with chronic hepatitis C infection and Covid-19 patients. The long-term follow-up of the patients with chronic hepatitis B infection showed that hepatitis B virus remained at low replication levels under the influence of the therapy, which made it possible to avoid such formidable complications of the disease as cirrhosis of the liver and liver cancer.

THE PHYSICAL PROPERTIES OF POLY(2-HYDROXYETHYL METHACRYLATE)COPOLYMER HYDROGELS USED AS INTRAVAGINAL RINGS

Poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) [P(HEMA-co-SMA)]hydrogels with different compositions were prepared to be used as intravaginal rings,and their gelation time,water content,mechanical properties and morphology were investigated.The water content of PHEMA and P(HEMA-co-SMA) hydrogels decreased as the concentration of the monomer and the degree of crosslinking increased,while the water content significantly increased as the content of SMA,the hydrophilic monomer,increased.The increasing of the concentration of the crosslinking agent affected the tensile and flexural properties highly.The presence of a proper small amount of SMA also led the tensile and flexural modulus to move to a higher level.The results showed that P(HEMA-co-SMA) hydrogel with high drug load and good mechanical properties at optimum preparation conditions can be prepared for intravaginal rings to deliver nonhormonal contraceptives.These results may be applied to prepare better intravaginal drug delivery devices.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Compatible stability study of Xing NaoJing injection based on physical-chemical properties analysis

Objective:The clinical treatment of brain diseases is urgent. Xingnaojing (XNJ) injection is often used in combination with other injection drugs. Due to the possible interaction between the injections in vivo, the particle size, osmotic pressure, pH value change and component stability decrease, that is one of the important factors causing various adverse reactions. Based on the above situation, this study investigated the physical properties and chemical composition changes of XNJ injection and its compatibility solvent and 13 kinds of clinical injection, speculated the possible interactions between the drugs in vivo from the perspective of in vitro compatibility stability, find out the safety risks of adverse reactions and provide guidance for the safe and rational use of XNJ injection. Methods:According to the clinical application, XNJ injection was mixed with 13 combination injections based on 250 mL 5% glucose injection, and placed at room temperature for 6 h. Then, the clarity, particle size, pH, osmolality, and the contents of camphor, d-borneol, and muscone of the compatible solutions were detected at 0, 1, 2, 4, and 6 h, respectively. Results:The results showed that the physical-chemical properties of compatibility solution were slightly influenced when XNJ was combined with Alprostadil injection and Danhong injection. The change of particle size and the degradation of muscone content were the main factors affecting the compatibility stability of XNJ injection, indicating that there are some problems in compatibility stability, which may be one of the causes of clinical adverse reactions. Conclusion:This study suggests that XNJ injection in combination with other injections during intravenous administration should be performed cautiously.

可吸收载药手术缝合线制备技术研究进展

可吸收载药手术缝合线已在医学缝合领域得到广泛应用,在业界展现了巨大的实践价值,并呈现出巨大潜力与广阔前景。回顾了可吸收缝合线的发展历程,详细介绍了可吸收载药手术缝合线的原材料、制备方法和载药方式。研究表明,可吸收载药手术缝合线是未来手术缝合线的发展方向,它们具有一定的强度并能递送药物,兼具可降解的特性,虽然可吸收载药缝合线性能优良,但仍需要在材料、工艺上改进以获得更好的发展。

武汉地区住院患者克罗诺杆菌感染及其临床分离株分子特征与耐药性研究

目的:研究武汉地区住院患者克罗诺杆菌感染及其临床分离株分子特征与耐药性。方法:选取2021年6月~2022年5月在武汉市第一医院就诊的克罗诺杆菌感染住院患者137例为研究对象,对患者克罗诺杆菌分离株行血清型分型鉴定、脉冲场凝胶电泳(PFGE)分子分型分析、克隆群结构特征分析与耐药性检验。结果:483例患者检出克罗诺杆菌感染137例,总检出率28.36%。男、女检出率差异无统计学意义(P>0.05),年龄分布以低龄(0~6岁)检出率最高,科室分布以儿科检出率最高,感染后易发疾病类型为脑膜炎(P<0.05);血清型分型鉴定以O 1为主要血清型分型,占比36.50%(50/137),ST型分布以ST4、ST1为主,分别占比40.15%(55/137)和31.38%(43/137),CC结构特征以CC4、CC7为主,分别占比32.85%(45/137)和40.15%(55/137);经内切酶Xba I和Spe I酶切后,分成14个PFGE图谱类型,其中BQ9、BQ11和BQ12相似系数较高(98.0%);耐药性检验结果提示,氨苄西林的耐药性较强(67.15%),对测定的其他抗生素全部敏感,未发现多重耐药菌株。结论:武汉地区住院患者克罗诺杆菌感染血清型分型以O 1型为主,PFGE分子分型具有多样性,其中氨苄西林的耐药性较强。

脂质体的制备方法及应用的研究进展

目的综述脂质体的制备方法及应用的研究进展,旨在为脂质体的进一步研究与开发新功能提供思路。方法查阅近年来国内外关于脂质体研究的相关文献,并对其进行整理、归纳与总结。结果脂质体作为近几十年发现的一种高效载体,可由人工合成的磷脂化合物来制备,且制备方法日益完善,可根据药物的不同特性对脂质体进行结构修饰,在医药、基因工程、食品、化妆品等领域起着越来越重要的作用。结论脂质体在药物治疗及生活中有着重要的研究意义与应用前景。

张锡纯运用牛膝探析

张锡纯溯源《神农本草经》,在继承前人认识的基础上,通过多年临床与思考,不断深化对牛膝的认识,在著作《医学衷中参西录》中对牛膝的用法用量、主治范围及药物配伍做出了详细精当、独具匠心的论述,并创制了许多牛膝新方。张锡纯不为功效所拘,而是以药性为主导,重视牛膝沉降之作用趋势及善下行之性,常用量在11~37 g不等,临床以引血下行为核心,用其通降上逆之气、火、水液,并载药下行,广泛用于心脑血管、头面五官、下肢、妇科、泌尿、消化等疾病中。同时,张锡纯也十分重视牛膝的配伍,如镇逆之牛膝配赭石,温通之牛膝配黄芪,引经之牛膝配桂枝。张锡纯应用牛膝的经验打破了常规思路,在继承的基础上勇于创新并留下了大量医案,为后世医家提供了用药方法与思路。

pH响应型抗菌水凝胶伤口敷料的制备及促愈合性能

文中利用衣康酸(IA)、丙烯酰胺(AM)和烯丙基三甲基氯化铵(TAAC)为原料发生进行交联,负载抗菌药物聚六亚甲基盐酸胍(PHMG),一锅法制备了pH敏感性抗菌水凝胶IA/AM/TAAC@PHMG。对水凝胶的力学性能、溶胀性能、释药性能、抗菌性能、生物相容性及促感染伤口愈合性能进行了研究。结果表明,TAAC能增加水凝胶的柔韧性,使水凝胶的断裂伸长率提高了88%;水凝胶具有pH响应性,能积极响应伤口pH,控制和延长PHMG的释放,PHMG在碱性条件下(pH 8.2)的释放率(60.65%)优于酸性条件(pH 3.2)下的释放率(14.97%);IA/AM/TAAC@PHMG对大肠杆菌和金黄色葡萄球菌的抑菌率大于99.98%;水凝胶组(320μg/mL)的细胞相对存活率高于75.08%,细胞溶血率小于4%,抗菌水凝胶具有良好的生物相容性;组织学分析证明IA/AM/TAAC@PHMG载药水凝胶能通过创造湿润低氧利于肉芽生长的环境和优异的抗菌性能,使炎性因子减少,促进胶原和皮肤再生,加速伤口愈合。

一株具有多种毒力基因的粪肠球菌噬菌体的研究分析

以之前分离出的奶牛乳房炎源粪肠球菌SL22为宿主菌,从临床型乳房炎乳样中分离纯化噬菌体,对其进行生物学特性分析、小鼠治疗试验及毒力基因与耐药基因检测。结果分离到1株噬菌体,该噬菌体形成的噬菌斑如针尖状,电镜下发现该噬菌体无尾,头部呈对称多面体,直径约66 nm,将其命名为vB_Eco T_PSL22(简称PSL22);只裂解其宿主菌,核酸类型为dsDNA;最佳感染复数为0.1,裂解量约为52 PFU/cell;在p H4.0~12.0时活性稳定,能耐受60℃左右高温。对小鼠治愈率为33.33%(2/6),含有2个耐药基因(Acc和aac(3)-Ⅳ)和4种毒力基因(gelE、cylA、ace和efaA)。通过本次试验,可为临床型乳房炎奶牛乳房中噬菌体的多样性研究提供参考,也可为研究奶牛乳房中的微生态系统提供依据。

PCL/ASA药物控释系统结构拓扑优化及瞬态释药性能

以聚己内酯(PCL)为载体材料,阿司匹林(ASA)为待释放药物,提出一种PCL/ASA药物控释系统,以实现医工结合背景下药物控释系统的个性化定制及释药量的参数化调节。首先,基于菲克扩散定律建立了PCL/ASA药物控释系统的释药模型,以设计域平均浓度与目标浓度之差的最小值作为优化目标,采用拓扑优化方法对PCL/ASA药物控释系统的结构进行拓扑优化设计。其次,对所获得的拓扑优化结构进行几何重构,得到清晰的流道结构,并研究了不同药物储库形状和流道结构对瞬态释药性能的影响。最后,制备PCL/ASA药物控释系统并进行体外药物释放实验,验证了优化方法和模型的合理性。结果表明,几何重构方法可以很好地保留拓扑优化的流道结构,具备较高的可靠性。拓扑优化方法所获得的流道结构展现出较好的药物控释性能,药物释放趋势趋于零级释放。基于拓扑优化设计的PCL/ASA药物控释系统可以在35.03~43.86 mol/m3范围内实现ASA浓度的参数化调节,呈现出较好的释药量调节能力。该研究为医工结合背景下优化药物控释系统结构、实现按需给药提供了一种新的手段。

壳聚糖治疗牙周病的研究进展

壳聚糖是迄今为止发现的唯一天然存在的阳离子多糖,因具有良好的生物相容性、生物降解性、抗菌、抗炎、抗癌、组织修复活性和巨大载药能力等优点,在组织工程中逐渐受到重视。作为一种炎症破坏性疾病,牙周病发病率高且对口腔健康乃至全身健康都有重大影响。本文总结了壳聚糖在牙周治疗中的再生支架、药物递送、抗菌作用、抗炎和促进血管生成作用等,分析了目前存在的问题,指出了未来可能的发展方向,旨在为牙周病的治疗提供新思路。

常见毒品检测方法研究进展

当前毒品滥用问题在世界范围内仍持续蔓延,制毒的方式不断更新,贩毒的手段日益隐蔽,毒品类型的隐蔽性和迷惑性不断增强,毒品进入人体后导致机体功能障碍甚至死亡,严重危害人类健康和社会公共安全。为了进一步打击毒品犯罪、开展禁毒工作、追溯毒品来源,必须提升毒品检测的分析能力,积极研发准确、高效、快速和安全的分析检测技术,为毒品案件的侦查提供线索,为案件的侦破提供有力的证据。鉴于此对常见毒品的危害、理化性质、毒理作用和检验方法等方面的研究进展进行综述。

Astragalus membranaceus(Fisch.)Bge.administered by dissolving microneedles achieves systemic therapeutic effects at low doses Author links open overlay panel

Objective:To determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo efficacy,and to analyze drug diffusion using dissolving microneedle(DMN)technology in vivo.Methods: Respectively,AIV-and AP-loaded DMNs comprising chitosan(CTS)and polyvinyl alcohol(PVA)were prepared via dual-mold forming.Their morphology,mechanical properties,in vivo solubility,and skin irritation characteristics were tested.In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice,in vivo diffusion of AIV and AP by DMNs and conventional methods was compared,and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured.Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles(MNs)at low doses(50%–17%of intraperitoneal AIV injection and 12%–4%of intravenous AP injection)reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models,increased the thymus index,and achieved equivalent or better systemic therapeutic effects.Compared with injections,AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs,resulting in highly localized aggregation within 48 h,reducing the initial explosive effect of the drug,and achieving stable and slow drug release.Conclusion: The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine(TCM)perspective,thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.

喹啉酮类BRD4抑制剂的3D-QSAR研究

使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮类抑制剂。结果表明,建立的CoMFA(q^(2)=0.926,r^(2)=0.997,r^(2)_(pred)=0.744)和CoMSIA(q^(2)=0.939,r^(2)=0.991,r^(2)_(pred)=0.786)模型具有较好的预测能力,基于这些模型设计的7个新喹啉酮类BRD4抑制剂具有高活性,并对其进行ADMET性质评价和类药性分析。以上研究结果有助于改造和开发更加有效的喹啉酮类BRD4抑制剂。

药品相关专利挖掘方法的探讨和分析

国内药物开发受自身技术实力及研发投入影响,进入的时间较发达国家的医药龙头企业晚很多,多以仿制药为主。近年来,随着我国国家知识产权强国战略的逐步推进,医药企业由仿制向自主创新的模式转变已成为大势所趋,知识产权的重要性日渐凸显,知识产权,特别是专利逐渐成为企业提高国内外与国际市场核心竞争力的重要资产。本文从专利挖掘的角度进行分析,讨论小分子化药的专利申请思路,为医药企业和科研单位提供参考。

屎肠球菌Ef026的体外益生特性研究

本试验旨在探究屎肠球菌Ef026的体外益生特性,挖掘其开发成饲用微生物制剂的潜力。通过对菌株的耐受性、细胞表面特性、抑菌作用、抗氧化作用及药敏试验,全面评价了其体外益生特性。结果显示:屎肠球菌Ef026在pH 3.0及0.3%的胆盐浓度下具有良好的耐受性;能够耐受70℃高温;具有极高的黏附性,其黏附指数为(38.00±1.67)%;对多种畜禽和水产养殖中常见病原菌具有一定的抑制作用;菌株完整细胞能够耐受2.0 mM H_(2)O_(2),同时还具有还原能力、DPPH·清除力、·O_(2)^(-)清除力和抗脂质过氧化能力;对常用抗生素具有不同程度的敏感性。屎肠球菌Ef026具有优良的体外益生特性,具有开发成饲用微生物制剂的价值。

多基原藏药噶吾尔的本草考证

噶吾尔是藏医临床治疗热性疾病的基础药之一。通过查阅藏医药古籍文献资料,结合地方标准,对其不同基原的用药标准、名称、别名、基原、炮制、药性、化学成分、药理作用等进行研究,并对用药混乱现象等进行梳理分析。研究发现,噶吾尔最早记载于《月王药诊》,后逐渐以标准名噶吾尔记载于《四部医典》及各类以四部医典注释为主的藏医药学著作中。经本草考证,11世纪前的古籍文献中未见噶吾尔的优劣之分,12世纪起被分为3类,即布玛拉树(■)树脂叫芒噶吾尔,甘赞树(■)树脂叫达色噶吾尔,沧岗树(■)树脂叫谢噶吾尔。查阅资料得知,来源与产物、时间及季节分为9种,强下品为冰片Borneol campho-ra,弱下品为艾片Camphor、龙脑香Dryobalanops aromatica Gaertn.f、艾脑香(艾纳香)Blumea blsamifera(L.)DC;强中品为薄荷脑Mentha haplocalyx Briq,弱中品为薄荷Mentha haplocalyx Briq;强上品为樟脑Camphora,弱上品为云南樟Cinnamomum glandu-liferum(Wall.)Nees、樟木Cinnamonum cam-phora(L.)Persl。经过对比临床常用的9个品种,其功效相近,且已知主要化学成分均为挥发油和萜类等。噶吾尔的本草考证将为藏医临床的科学、合理用药和质量标准建立提供理论参考。