P(γ-PGA-co-NIPAAm)水凝胶对5-氟尿嘧啶药物分子的释放行为

以γ-聚谷氨酸(γ-PGA)、N-异丙基丙烯酰胺(NIPAAm)为单体,通过自由基共聚法制备一种水凝胶缓释材料。采用扫描电镜观察水凝胶的多孔断面形貌,并研究不同温度(25℃和37℃)下水凝胶表面的亲疏水性和不同pH(2.0~10.0)时的溶胀率变化。将该共聚水凝胶用作药物缓释载体,通过紫外分光光度计法研究其对5-氟尿嘧啶(5-FU)药物分子的缓释行为。结果表明:该凝胶在酸性条件下释药速率最快,碱性条件下次之,中性条件下释放最慢,25℃下释放量与γ-PGA含量呈正相关,37℃下结果相反;该凝胶具有温度、pH双敏感性,在弱碱性条件下释放缓慢、释药量小,具有一定的靶向释药能力。     

温度和pH双敏性PVME/CMCS水凝胶辐射交联制备及其性能

以聚甲基乙烯基醚(PVME)和羧甲基壳聚糖(CMCS)为原料, 采用电子束辐照交联方法制备聚甲基乙烯基醚/羧甲基壳聚糖(PVME/CMCS)水凝胶, 研究了温度、pH值、CMCS含量等对PVME/CMCS水凝胶溶胀度的影响, 同时以5-氟尿嘧啶(5-Fu)作模型药物, 初步探讨了凝胶药物释放性能. 结果表明, 辐射剂量在20—40 kGy时, 凝胶分数随辐射剂量的增加而快速增加, 辐射40 kGy以后趋于平衡. 在相同辐射剂量下, 随着体系中CMCS含量的增加, 凝胶分数反而减少. 该水凝胶具有一定的温度和pH敏感性, 其低临界溶解温度(LCST)在35 ℃左右, 并且在相同时间内和25及37 ℃下的溶胀反复可逆, 表现出较快的响应性. pH<3.0和pH>5.0时, 溶胀度较大; pH值为3.0~5.0时, 凝胶网络由于静电力收缩, 溶胀度较小. CMCS含量的增加和辐射剂量的减小均可提高凝胶载药量. 药物释放时间可通过改变体系中CMCS的含量和辐射剂量来调节.     

CMC/PNIPAAm半互穿网络水凝胶的溶胀动力学研究

以羧甲基纤维素钠(CMC)和N-异丙基丙烯酰胺(NIPAAm)为原料,制备了具有温度和pH敏感性的半互穿网络(CMC／PNIPAAmsemi-IPN)水凝胶,并研究了水凝胶在不同温度和pH值条件下的溶胀行为。结果表明：在弱碱性(pH-7．4)条件下,凝胶的溶胀速率和溶胀度都随着凝胶中CMC含量的增加而增大;而在酸性(pH-1．O)条件下则相反。在弱碱性条件下,水分子在凝胶中的扩散行为都可用non-Fickian扩散来描述,水分子在凝胶中的扩散系数D随着凝胶溶胀速率的增大而增大;在酸性条件下,20℃时凝胶的溶胀过程符合non-Fickian扩散规律,而37℃时凝胶的溶胀过程符合Fickian扩散规律,但水分子的扩散系数D相差不大。     

PEGDA/NIPAM共聚物水凝胶的药物释放性能研究

以IRGACURE2959为光引发剂,聚乙二醇双丙烯酸酯(PEGAD)和N-异丙基丙烯酰胺(NIPAM)为单体,通过紫外光引发光聚合,合成了PEGDA/NIPAM共聚物水凝胶,研究了凝胶于不同酸度介质及不同温度中对阿司匹林的释放行为。结果表明,模拟胃肠液中,随释放时间的延长,载药凝胶对药物的累积释放率增加。NIPAM单体的引入增大药物累积释放率,药物缓释时间延长,具有良好的药物释放性能。凝胶对药物的缓释受温度与释放时间的影响,在37℃和45℃时,随释放时间增加,药物累积释放率增大;在30℃时,随释放时间的增长,累积释放率先增大后减小。     

NIPAAm系互穿网络凝胶的合成及载药释药性能研究

合成了三种亲疏水性不同的温度及pH敏感的PAAc／P（NIPAAm-co-BMA）、PAAc／PNIPAAm和PAAc／P（NIPAAm-co-AAm）互穿网络（IPN）水凝胶,以水杨酸钠和水杨酸为模型药物,研究了温度、pH值及药物和凝胶的亲疏水性相互作用对模型药物释药性能的影响。研究结果表明,随着凝胶亲水性的增强,水杨酸钠的载药率提高,释药率也越大;相反疏水性增强也有利于提高水杨酸的载药率;IPN凝胶在水中的释药过程属于溶胀支配型释放,药物释放率随凝胶的亲水性增强而增强,同时,载药凝胶在45℃水中的释药率大于25℃时的释药率。在25℃时,水杨酸在pH=2．2的缓冲溶液中几乎不释放,而在pH=7．4的缓冲溶液中能以较快的速率释放。     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

温度敏感性壳聚糖基聚电解质载药纳米粒子的制备及表征

以天然高分子壳聚糖(CS)、羧甲基纤维素(CMC)和温度敏感性单体N-异丙基丙烯酰胺(NIPAM)为原料,通过自组装制备了温度敏感性聚电解质复合纳米粒子CS-g-PNIPAM/CMC-g-PNIPAM,并以5-氟尿嘧啶(5-FU)为模型药物研究了纳米粒子对药物的负载与可控释放性能。当CMC-g-PNIPAM与CS-g-PNIPAM的质量比为3:7时,形成的纳米粒子结构最稳定,动态光散射(DLS)测得其平均粒径为116nm,粒径分布较窄。载药纳米粒子对5-FU具有较高的载药量和包封率。在磷酸盐缓冲溶液中的释药行为表明,其累积药物释放量随pH和温度的增加而增大,表现出良好的pH与温度可控性能。     

先辐射后冻融法制备聚乙烯醇/水溶性壳聚糖/甘油水凝胶的云南白药药物释放性能研究

采用先辐射后冻融的方法制备了一系列聚乙烯醇(PVA)/水溶性壳聚糖/甘油水凝胶,通过浸泡法在水凝胶中载入云南白药,并且研究了溶液pH值、离子强度、冻融次数和PVA浓度对水凝胶溶胀性能和云南白药释放性能的影响.研究发现水凝胶的溶胀度随溶液离子强度的增大而下降,且酸性溶液大于中性溶液.水溶性壳聚糖的加入有利于云南白药载入凝胶,同时使云南白药的释放具有pH和离子强度敏感性.云南白药的释放量在模拟体液中最大,在中性溶液中次之,在水和酸性溶液中最小,与溶胀度变化关系相反.而水凝胶的溶胀度和云南白药释放量均随冻融次数和PVA浓度的增大而下降.分析表明,云南白药在不同介质中的释放量主要取决于药物和溶液中离子的交换能力;在相同介质中,不同凝胶的药物释放量受溶胀度影响明显.凝胶溶胀速率远大于药物释放速率说明后者主要由扩散过程控制.药物释放的pH敏感性表明该水凝胶具备用作云南白药的口服载体的潜力.     

温敏性PNIPAAm水凝胶对布洛芬的控制释放

采用自由基聚合法在水溶液中制备了温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm),以非水溶性药物布洛芬(IBU)为模型药物分子,研究了该水凝胶的温敏性能及与药物IBU的相互作用,考察了不同温度下(25 ℃和37 ℃)IBU在磷酸盐缓冲溶液(PBS,pH=7.4)中的释放行为.研究结果表明:该水凝胶的最低临界溶解温度(L...     

壳聚糖/聚乙二醇/聚丙烯酸复合水凝胶的制备及药物控制释放行为研究

本文以壳聚糖(CS)、聚乙二醇(PEG)和丙烯酸(AA)为原料,制备了复合水凝胶CS/PEG/PAA。研究了负载四种具有不同结构和性质的药物(烟酸、烟酰胺、异烟肼和5-氟尿嘧啶)的复合水凝胶CS/PEG/PAA的药物控制释放行为。结果表明,烟酰胺和异烟肼在pH=1.80的缓冲溶液中的药物累积释放率(R)大于其在pH=6.86的缓冲溶液中的释放率;烟酸却在pH=6.86的缓冲溶液中的药物累积释放率(R)大于其在pH=1.80的缓冲溶液中的释放率。而5-氟尿嘧啶在两种缓冲溶液中的药物累积释放量相当。因此,复合水凝胶CS/PEG/PAA也许可以作为一种新型释放药物的载体。     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.     

Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Both substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles have been synthesized by the 3+2 intramolecular dipolar cycloaddition of nitrilimines to alkynes. This cyclization has been extended to more versatile 3-bromo derivatives by the use of alkynylbromides as dipolarophiles.