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    中國抗生素雜志

    中國抗生素雜志

    北大核心

    CSCD

    CSTPCD

    Chinese Journal of Antibiotics
    《中國抗生素雜志》（Chinese Journal of Antibiotics）創刊于1976年，是我國目前抗生素及微生物藥物領域唯一的專業性學術核心期刊。其理念是“專注抗生素、服務產學研，辦中國抗生素領域最好的核心刊”；其宗旨是宣傳報道我國抗生素及微生物藥物科研、生產、臨床應用等方面研究進展。該刊具有嚴謹的科學性、較高的學術性及行業的情報性，是我國科技論文統計源期刊、自然科學核心期刊，被國內幾乎所有數據庫、文獻檢索系統收載，是我國抗生素及微生物藥物領域學術交流的重要平臺。
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    • 發文量：0
    • 被引量：1741
    • H指數：3
    • 開始收錄時間：1989,14(1)
    • CNKI綜合因子：1.123
    • 維普期刊影響因子： 1.415
    • 萬方期刊影響因子：1.24
    • 創刊時間：1976
    • 國內刊號/CN：51-1126/R
      國際刊號/ISSN：1001-8689
    • 發行周期：月刊
      郵發代號：62-193
    • 主管單位：中國醫藥集團總公司
      主辦單位：中國醫藥集團總公司四川抗菌素工業研究所；中國醫學科學院醫藥生物技術研究所
    中國抗生素雜志-聯系信息
    • 主編：劉昌孝
    • 電話：028-64867191 84618674
    • 郵箱：siiacjap@126.com
    • 地址：成都市成華區華冠路168號
    • 郵編：610052
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    • 摘要：Shigella is one of the common pathogenic bacteria responsible for gastrointestinal infection. The vulnerable population are infants, elders and the immunocompromised. Shigella sonnei is most prevalent in developed countries and is becoming more prevalent in developing countries that have been dominated by Shigella flexneri. In this review, the distribution of Shigella sonnei, the situation of drug resistance, the mechanism of drug resistance and detection of Shigella sonnei were reviewed.%志賀菌是引起胃腸道感染主要病原菌之一.老人、兒童和免疫受損的患者中多發.發達國家流行的主要是宋內志賀菌,而發展中國家雖然長期以來流行的為福氏志賀菌,但近年來宋內志賀菌呈明顯增加的趨勢,并成為優勢菌群.本文就近些年全球宋內志賀菌的分布流行、耐藥情況、耐藥機制以及檢測方法的進行綜述.
    • 摘要：目的 針對現行HPLC方法的不足之處,采用膠束電動色譜技術檢測注射用哌拉西林鈉三唑巴坦鈉的雜質譜.方法 方法建立過程中分別采用壓力輔助-膠束電動色譜和短端進樣法對藥品中的有關物質進行篩查,以便得到較為完整的雜質譜和分析目標；為證實分離系統的專屬性和有效性,分別采用雜質對照品、半制備HPLC和梯度洗脫HPLC-電噴霧離子阱質譜對雜質譜中的主要雜質進行了確認.結果 采用該方法,9個已知雜質、其他未知雜質、哌拉西林以及三唑巴坦之間均分離良好.新方法可對注射用哌拉西林鈉三唑巴坦鈉的雜質進行更為有效而全面的分離分析.結論 該方法可應用于注射用哌拉西林鈉三唑巴坦鈉的雜質譜檢測.%Objective Considering the shortcoming of current HPLC methods, a micellar electrokinetic chromatography method was established to detect the impurity profile of piperacillin sodium and tazobactam sodium for injection. Methods In order to obtain full impurity profile, the pressure-assisted micellar electrokinetic chromatography and the "short-end-injection" technique were utilized during the method development. Impurity reference standards, semi-preparative HPLC, and gradient HPLC-electrospray ion trap mass spectrometry were used to confirm the selectivity and validity of the separation system. Results The novel method could provide efficient and comprehensive separation for the impurities of piperacillin sodium and tazobactam sodium for injection. Conclusion Using the novel method, nine known impurities, other unknown impurities, piperacillin and tazobactam could be separated. This method can be used for the impurity profiling of piperacillin sodium and tazobactam sodium for injection.
    • 摘要：Objective To explore the presence of 16S rRNA methylase genes in Acinetobacter baumannii which is double-circle resistant to aminoglycoside antibiotic in K-B methods, and to analyze the expression levels of resistance genes mRNA among strains induced and non-induced by amikacin. Methods A total of 42 strains of Acinetobacter baumannii were collected to test the antibiotic susceptibility by disk diffusion method. The three kinds of 16S rRNA methylase genes-armA, rmtB and rmtC were amplified by PCR. The genes expressions in drug-induced strains and non-induced strains were respectively measured by PT-PCR. Results About 90.4%(38/42) of strains showed the phenomenon of double-circle resistance. The armA was detected in these strains, but the rmtB and rmtC were not found. In other strains, 3 strains showed susceptible and 1 strain showed common resistant, and thel6S rRNA methylase genes were not found in these four strains. The result of PT-PCR revealed that the expression level of armA gene mRNA was significantly up-regulated when the strains were induced by amikacin. Conclusion The phenomenon of double-circle is possibly associated with the inducible expression ofarmA.%目的 探討在K-B法藥物敏感試驗中對氨基糖苷類藥物雙圈耐藥的鮑曼不動桿菌16S rRNA甲基化酶基因攜帶狀況以及藥物誘導對該基因mRNA表達量的影響.方法 收集42株鮑曼不動桿菌,K-B法測定其藥敏情況；PCR法擴增三種16S rRNA甲基化酶基因armA、rmtB及rmtC;用RT-PCR的方法分析阿米卡星誘導前后耐藥基因表達量.結果 90.4％(38/42)的菌株阿米卡星藥敏紙片周圍呈現雙圈耐藥,且均檢測到armA,未檢測到rmtB及rmtC,其余3株為敏感,1株為普通耐藥,且PCR檢測耐藥基因為陰性.RT-PCR結果顯示經阿米卡星誘導后細菌armA基因mRNA表達量顯著上升.結論 雙圈耐藥現象與armA基因誘導型表達有關.
    • 摘要：目的 介紹了近年來雷帕霉素及其衍生物的開發現狀、作用機制與生物合成途徑,探討了通過前體定向生物合成與誘變生物合成的方式,獲得雷帕霉素衍生物的研究進展,展望了雷帕霉素及衍生物的研究前景.方法 分析、歸納、總結近年來發表的相關文獻.結果與結論 雷帕霉素及其衍生物是新型強效的免疫抑制劑與抗腫瘤藥物,具有抗真菌、抗增殖及潛在延長哺乳動物壽命周期等作用.采用前體定向生物合成、誘變生物合成與組合生物合成的方式,可快速獲得其具藥理活性的衍生物.基于生物合成途徑,采用系統生物學相關手段可獲高產工程化菌種應用于工業化生產.%Objective The recent development situation, mechanism and biosynthesis of rapamycin and its derivatives were reviewed, and the research prospect of rapamycin and its analogs were further forecasted. Methods The literatures published in recent years were analyzed and summarized. Results and Conclusion Rapamycin and some its analogs are new potent immunosuppressive and anticancer drugs, which have obvious effects on anti-fungal, anti-proliferation, and the potential to extend the lifespan of mammalian and so on. By the ways of precursor-directed biosynthesis,mutational biosynthesis and combinatorial biosynthesis, some novel analogs of rapamycin can be obtained,and the high-yield strains tend to be reconstructed for industrial production by the means of system biology.
    • 摘要：Objective To screen for FADH2-depedent halogenase positive strains for finding natural halometabolites by mining actinomycetes genome DNA. Methods The novel halogenase gene-specific primers, according to ten known FADH2-dependent halogenases, were designed to amplify the conserved regionsin of this protein from 200 actinomycetes strains. Then, the amino acid sequence identities of putative halogenase gene-positive strains were alignmented in the datebases of GenBank. In addition, HPLC-MS method was used to elucidate the halogenase positive strain 1076 fermentation broth. Results Fifty-one positive strains were screened by this method. Based on the morphological, physiological and biochemical characteristics, as well as the sequence analysis of 16S rRNA, strain 1076, which displayed 99% homology to the halogenase sequence of enduracidin producing strain S. Fungicidicus, was identified as S. Macrosporeus. A further HPLC-MS analysis verified that this strain produces compounds enduracidin as predicted. Conclusion Strain 1076 was identified as S. Macrosporeus and was a novel enduracidin producing strain.%目的 篩選FADH2-鹵化酶陽性菌株發現天然鹵化物.方法 設計新的簡并引物對200株放線菌基因組鹵化酶基因擴增以篩選陽性菌株,并進行比對分析；對陽性菌株進行分類鑒定,對其代謝產物進行HPLC-MS分析.結果 篩選得到到51株陽性菌,其中一株與恩拉霉素的同源性為99％.對該編號為1076的菌株進行的分類鑒定結果,確定為Streptomyces macrosporeus.對其代謝產物進行的HPLC-MS分析顯示,其代謝產物與恩拉霉素同質.結論 鹵化酶陽性菌株1076屬于S.macrosporeus的一個菌株,是新的恩拉霉素產生菌.
    • 摘要：目的 通過研究前體對多拉菌素生物合成的影響,尋找提高多拉菌素發酵產量的有效方法.方法 本文主要考察了不同前體對多拉菌素生物合成的作用,以及有效前體的最佳添加濃度和添加時間.結果 丙酸鈉是多拉菌素合成的最佳前體,在發酵96h時添加0.1％的丙酸鈉,多拉菌素產量達139.89μg/mL,比對照組提高了38.2％.結論 前體的供給能顯著影響多拉菌素的生物合成,補加丙酸鈉能有效提高多拉菌素的發酵產量.%Objective Exploring an effective method of increasing doramectin productivity of Streptomyces avermitilis with the research of feeding of doramectin precursors. Methods The effects of different precursors on the biosynthesis of doramectin, the optimum concentration and feeding time of the effective precursor were studied. Result Sodium propionate was the optimal precursor for doramectin biosynthesis. By feeding of 0.1% sodium propionate into the fermentation broth at the 96th hour of cultivation, the doramectin production was 139.89μg/ mL,38.2% higher than that in the condition without any addition of precursor. Conclusion The feeding of precursors has significant influence on the doramectin biosynthesis and the addition of sodium propionate is effective in increasing doramectin production.
    • 摘要：目的 對比市售產品注射用頭孢匹胺與注射用頭孢匹胺鈉的質量及穩定性.方法 通過影響因素試驗、加速試驗、長期留樣試驗,考察市售產品注射用頭孢匹胺和注射用頭孢匹胺鈉的穩定性.結果 注射用頭孢匹胺的質量較好,產品較穩定；注射用頭孢匹胺鈉的質量較差,穩定性留樣顏色、聚合物、有關物質、含量變化均有明顯變化.結論 注射用頭孢匹胺產品的質量穩定,有利于臨床用藥的安全.%Objective Compare the quality and stability of commercially available products between cefpiramide for injection and cefpiramide sodium for injection. Methods By influencing factor testing, accelerated testing, long-term testing to study commercial products of cefpiramide for injection and cefpiramide sodium for injection. Results Cefpiramide for Injection is better quality and more stable product; cefpiramide sodium for injection of poor quality, Stability tests showed that the color, polymers, related substances, content changed significantly. Conclusion Cefpiramide for injection of better quality and stability, conducive to the safety of clinical medication.
    • 摘要：Objective To investigate the relationship between the genetic polymorphisms of glutathione S-transferase Ml, T1(GSTM1, GSTT1) and the susceptibility of antituberculosis drug-induced hepatotoxicity (ATDLI) in the tuberculosis patients of Chinese Han population. Methods Genetic polymorphisms of GSTM1, GSTT1 were analyzed in tuberculosis patients treated with or without hepatotoxicity after antituberculosis drug using multiple PCR method. Resultes The frequencies of GSTM1 null genotype were 58.3% in the ATDLI patients and 50.7% in controls (OR=1.363, 95%CI=0.963~1.929), which the difference was not significant (P>0.05). The frequencies of GSTT1 null genotype were 45.2% in the ATDLI patients and 49.3% in controls, which the difference was also not significant (P>0.05). The variation frequency of the combination of GSTM1 and GSTT1 between case group and control group had not statistically difference (P>0.05). They had not synergistic effect in the development of ATDLI. Conclusion GSTM1 and GSTT1 genotypes might have no association with risk of the ATDLI in Chinese Han population.%目的 探討漢族人群谷胱甘肽S轉移酶M1(GSTMl)和T1(GSTT1)基因多態性與抗結核藥物性肝損害(ATDLI)易感性的關系.方法 回顧性分析抗結核治療后發生肝損害的結核病患者228例(病例組)及未發生肝損害的結核病患者300例(對照組),應用多重PCR技術檢測其GSTM1和GSTT1基因多態性.結果 病例組與對照組GSTM1基因缺失型頻率分別為58.3％和50.7％,差異無統計學意義(OR=1.363,95％CI=0.963～1.929); GSTT1基因缺失型頻率分別為45.2％和49.3％,差異也無統計學意義.聯合分析也未發現兩種基因在抗結核藥物性肝損害發生中具有協同作用.結論 漢族人群GSTM1和GSTT1基因多態性與抗結核藥物性肝損害的發生無關.
    • 摘要：目的 觀察老年COPD患者應用卡泊芬凈治療侵襲性真菌感染(IFI)的療效與安全性.方法 回顧分析本院老年臨床醫學部呼吸內科診斷為IFI并接受卡泊芬凈治療的COPD患者的臨床資料.結果 2009年10月～2010年12月共36例COPD患者接受了卡泊芬凈治療,確診4例,包括念珠菌菌血癥2例(光滑念珠菌1例,熱帶念珠菌l例),肺IFI 2例,為曲霉菌；臨床診斷20例,其中曲霉菌15例,白念珠菌5例；擬診12例,包括白念珠菌6例,光滑念珠菌2例,近平滑念珠菌2例,曲霉菌2例.卡泊芬凈的療程(16.5±6.5)d,痊愈+顯效的總有效率72.2％,進步22.2％,無效5.6％.治療過程中未發現與卡泊芬凈有關的不良反應.結論 卡泊芬凈治療老年COPD患者合并IFI有效且安全.%Objective To evaluate the effect and safety of caspofungin in the treatment of invasive fungal infection (IFI) in old COPD patients. Methods A retrospective analysis of the clinical data was conducted for 36 old COPD patients with IFI and treated with caspofungin in elderly clinical respiratory department. Results From October 2009 to December 2010, 36 COPD patients with IFI were treated with caspofungin. Four patients were confirmed cases, including 2 candidemia (1 Candida glabrata, 1 C. Tropicalis), 2 pulmonary IFI (Aspergillus spp.). 20 clinical diagnosis cases consisted of 15 Aspergillus and 5 C. Albicans spp. There were 12 probable cases, including 6 C. Albicans, 1 C. Glabrata, 2 C. Parapsilosis and 2 Aspergillus. The mean treatment course of caspofungin was (16.5±6.5)d. The overall effective rate was 72.2%. No drug-related side effect or adverse event appeared. Conclusion Caspofungin is likely to be an effective and safe treatment for IFI in old COPD patients.
    • 摘要：Objective To establish a method for determination of the residues of 5 kinds of solvents by capillary gas chromatography. Methods The capillary column was DB-624(60m ×0.32mm × 1.0μm). Stationary phases: 6% cyanopropyl-phenyl, 94% demethyl polysiloxane, the carrier gas was nitrogen and FID as detector. The injector temperature was 200℃, and the detector temperature was 250℃, split-inject mode. Result Under the above condition, there is a good linear relationship in the concentration range measured, the recoveries are between 90.0% and 110.0%. Conclusion The method is simple, accurate and reproducible. It can be used for determination of 5 kinds of residue solvents at the same time.%目的 用毛細管氣相色譜法建立頭孢替坦二鈉中5種殘留溶劑的測定方法.方法 采用DB-624毛細管色譜柱(60m×0.32mm×1.0μm),固定相為6％氰丙基-苯基,94％二甲基聚硅氧烷,FID檢測器,載氣為氮氣,程序升溫,進樣口溫度200℃,檢測器溫度250℃,分流進樣模式,測定殘留溶劑的含量.結果 在各種的濃度范圍內具有良好的線性關系(5種溶劑的相關系數均為0.999以上),5種溶劑3個濃度的回收率均在90.0％～110.0％之間.結論 本方法專屬性強,操作簡便,結果可靠,可用于5種殘留溶劑的同時測定.
    • 摘要：Objective To evaluate the differences in susceptibility of Acinetobacter baumannii among different concentrations of cefoperazone-sulbaetam combination preparation. Methods Susceptibility test of two different concentrations was conducted by Agar dilution, E-test , VITEK- AMS , and disc diffusion method respectively. Results Differences of the susceptibility of Acinetobacter baumannii conducted by the four methods were notable. The data indicated that the consistency rate of the disc diffusion method was the lowest, and the antibacterial activity of cefoperazone-sulbaetam with the concentration of 1: 1 was prior to that of 2: 1. Conclusion It would be better to describe the concentration and method when reporting the susceptibility of cefoperazone-sulbeatam , then a more reliable guidance can be provided for clinical use.%目的 了解藥敏試驗方法檢測鮑曼不動桿菌對不同配比頭孢哌酮/舒巴坦制劑的體外敏感性差異.方法 分別采用瓊脂稀釋法、E-test法、K-B紙片擴散法和儀器法檢測2:1和1:1配比頭孢哌酮/舒巴坦對鮑曼不動桿菌的體外抗菌活性.結果 E-test、K-B紙片擴散法和儀器法的檢測結果與瓊脂稀釋法均存在一定的差異,其中紙片擴散法的符合率最低；1:1配比頭孢哌酮/舒巴坦制劑的體外抗菌活性高于2:1配比制劑.結論 建議實驗室報告頭孢哌酮/舒巴坦藥敏試驗時,說明試驗所用的兩種藥物比例和采用的檢測方法,以便臨床更好地利用體外藥敏結果選擇藥物.
    • 摘要：Objective To screen high yield broad-spectrum antifungal antibiotic breeding CA-SD07 producing strain. Methods Two kinds of breeding methods ultraviolet radiation (UV) and high concentration of phosphate screening after ultraviolet radiation (UV+Pi) were conducted. Inhibition zone method, fermentation with flash shaking and with small fermentor were applied in screening high yield strains. Results 25 strains were isolated from UV group, 12 strains were isolated from UV+Pi group, during the first round flash shaking screening. The relative yield of antibiotic CA-SD07 of all these 37 strains increased by 50% or more than that of the original strain SD-07. 6 strains were screened during the second round flash shaking screening from the above 37 strains, their relative yield of antibiotic CA-SD07 increased by 100% or more than that of the original strain SD-07. Finally, 1 mutant strain was isolated by the fermentation characteristics: Its relative yield of antibiotic CA-SD07 stably increased by 100% or more than that of the original strain SD-07, and its fermentation period reduced more than 24 hours. Conclusion UV and UV+Pi got similar breeding results, high concentration phosphate screening did not significantly improve the antibiotic production of the isolated strains, but could improve the ratio of high antibiotic yield isolates to the whole ones. This suggested: In order to improve production of antibiotics, it needed improve the existing methods for high concentration phosphate screening.%目的 擬通過紫外線誘變結合耐高濃度磷酸鹽篩選廣譜抗真菌抗生素CA-SD07的高產菌株.方法 采用兩種育種方式:紫外線誘變(UV),紫外線誘變后進行高濃度磷酸鹽抗性篩選(UV+Pi).篩選方法采用抑菌圈法、搖瓶發酵和小型發酵罐發酵.結果 經過搖瓶初篩和復篩,從UV組和UV+Pi組共篩選到6株抗生素相對產量比原始菌株提高100％以上的高產菌.通過發酵罐發酵試驗,選出1株抗生素相對產量穩定提高100％以上,且發酵周期縮短約24h的突變菌株.結論 UV+Pi與UV組育種效果接近,抗磷酸鹽篩選并沒有明顯提高抗生素產量的作用,提示利用抗磷酸鹽篩選高產菌株,需要在現行方法上進行改進才有可能實現.
    • 摘要：目的 了解格爾德霉素生物合成PKS后修飾過程中的一些細節.方法 對格爾德霉素產生菌吸水鏈霉菌17997及其格爾德霉素生物合成聚酮合酶(polyketide synthase,PKS)后修飾基因阻斷變株(gdmP-和gdmN-)在ISPII平板不同時間的培養物進行乙酸乙酯提取,硅膠板TLC和NaOH顯色分析,檢測GDM及其生物合成中間產物,并利用LC-MS對中間產物進行鑒定.結果 吸水鏈霉菌17997原株、gdmN-和gdmP-變株在培養時間72～96h,發現氫醌型格爾德霉素(GQH2)、氫醌型4,5-雙氫-7-去氨甲酰基-7-羥基格爾德霉素(H2GQH2-dC)和氫醌型4,5-雙氫格爾德霉素(H2GQH2)分別為主要組分,相應的醌型化合物為次要組分；之后,這些氫醌型化合物隨培養時間延長逐漸消失,相應的醌型化合物成為主要組分.雙向硅膠板TLC分析證實GQH2、H2GQH2-dC和H2GQH2均可在空氣中自發氧化為相應的醌型化合物.結論 在吸水鏈霉菌17997的GDM生物合成PKS后修飾過程中,首次提出GQH2自發氧化為GDM可能是氫醌型向醌型轉變的位點,同時它也是GDM生物合成最后一步.%Objective To obtain some detail(s) of the post-PKS tailoring process of geldanamycin (GDM) biosynthesis. Methods The ethyl acetate extracts of Streptomyces hygroscopicus 17997, its gdmN an&gdmp mutants on ISPII medium plates at different culture times were analyzed by silica gel TLC, followed by alkaline color reaction for preliminary discrimination of GDM and its biosynthetic intermediate(s) or LC-MS for confirming the interested GDM biosynthetic intermediate(s). Results At a culture period of 72~96h, geldanamycin hydroquinone (GQH2), 4,5-dihydro-7-descarbamoyl-7-hydroxygeldanamycin hydroquinone (H2GQH2-dC) or 4,5-dihydrogeldanamycin hydroquinone (HjGQH2) appeared as the main component, while the corresponding quinone as the minor component, of Streptomyces hygroscopicus 17997, its gdmN' or gdmR disruption mutant, respectively. These hydroquinones dissappeared gradually in older cultures, and that the corresponding quinones became the main components. Inaddition, these hydroquinones could be converted spontaneously to GDM, H2GDM-dC or H2GDM upon exposure to air by two dimentional silica gel TLC analysis. Conclusion Spontaneous oxidation of GQH2 to GDM is suggested as the last step of the post-PKS tailoring process of GDM biosynthesis in Streptomyces hygmscopicus 17997.
    • 摘要：目的 建立桿菌肽鋅菌落計數檢驗方法.方法 采用薄膜過濾法對桿菌肽鋅進行菌落數測定.結果 實驗表明以0.1％蛋白胨水和EDTA的混合溶液為稀釋液,0.1％蛋白胨水溶液為沖洗液的薄膜過濾法為菌落計數方法.結論 操作步驟簡單,檢驗結果準確,是有效可行的檢驗方法.
    • 摘要：目的 建立天藍淡紅鏈霉菌基因工程菌(SIPI-A0707)發酵液中表柔紅霉素的分離純化工藝.方法 調節發酵液pH值為5,用甲醇抽提表柔紅霉素；先采用大孔弱酸性陽離子交換樹脂D152,吸附流速為2mL/min,0.05mol/L HCl-50％丙酮解吸;然后采用氯仿-水萃取體系,萃取pH為6.5,反萃取使用pH為1.5的蒸餾水,最后采用大孔吸附樹脂Microsphere-1；吸附pH為7,吸附流速3mL/min,50％甲醇解吸分步收集,濃縮凍干.結果 表柔紅霉素HPLC純度達到98.1％,總收率為40％以上.結論 此工藝在生產上可行性較高,適合工業大量制備.%Objective To establish a separation and purification process of 4'-epi-daunorubicin from fermentation broth of gene engineering strain Streptomyces coeruleorubidus (SIPI-A0707). Methods Adjusted the pH value of fermentation broth to 5 and extracted 4'-epi-daunorubicin with methanol. Firstly macroporous weak acid cation exchange resin D152 was used and the adsorption flow rate was 2mL/min, 0.05mol/L HCl-50% acetone was used as desorption agent. Then chloroform-water extraction system was studied which showed the optimized extraction pH value was 6.5 and distilled water with pH 1.5 was used as reextraction agent. Finally macroporous resin Microsphere-1 was used and the adsorption pH value was 7, the adsorption flow rate was 3mL/min, 50% methanol was used as desorption agent and fractions were collected, decompressed and freeze-dried. Results The HPLC purity of 4'-epi-daunorubicin was over 98.1%, total yield was over 40%. Conclusion The extraction process of 4'-epi-daunorubicin is easy to scale-up for industrial preparation.
    • 摘要：目的 體外研究萬古霉素(vancomycin,VAN)分別與左氧氟沙星(levofloxacin,LVX)、利福平(rifampincin,RFP)、磷霉素(fosfomycin,FOM)聯用對降低對金黃色葡萄球菌防耐藥突變濃度(MPC)的比較,為指導臨床聯合應用抗菌藥物,制定新的用藥策略,防止細菌耐藥產生提供理論依據.方法 采用肉湯富集1010CFU/mL金黃色葡萄球菌ATCC29213,采用瓊脂平板二倍稀釋法測定單獨用藥的最低抑菌濃度(MIC),瓊脂平板稀釋法測定單獨應用VAN以及與其他三種藥物聯用對金黃色葡萄球菌ATCC29213的MPC.并計算出各藥單獨應用的MSW(MPC/MIC).結果 VAN、LVX、RFP、FOM單藥對金黃色葡萄球菌ATCC29213的MIC分別為1,0.125,0.008和2μg/mL; MPC分別為64,2,＞32,64μg/mL,MSW為64,6,＞4000,32.聯合用藥后各藥的MPC(μg/mL)降低程度如下:VAN+LVX (MPCNVA-4,MPCLVX-0.125),VAN+RFP(MPCNVA-4,MPCRFP-0.008),VAN+FOM(MPCNVA -1,MPCFOM-2).聯合LVX和RFP可使VAN的MPC降至原來的1/16倍,聯合FOM可使VAN的MPC降至原來的1/64倍.結論 VAN與另三種藥物聯用,可以明顯降低各自單獨用藥對金黃色葡萄球菌ATCC29213的MPC,其中聯合FOM降低其MPC幅度最大,縮小其MSW效果最好.%Objective To study the comparison of Vancomycin (VAN) separately combined with levofloxacin (LVX), rifampincin (RFP) and fosfomycin (FOM) for decreasing mutant prevention concentration (MPC) of Staphylococcus aureus in vitro, which direct rational applications of available antibiotics in clinic practice and provide evidence for new strategies for restricting the development of resistance. Methods The Staphylococcus aureus strain ATCC29213 was enriched the concentration to 1010 colony forming units per milliliter in broth. Minimum inhibitory concentration (MIC) of VAN, LVX, RFP and FOM alone was determined by agar plates dilution method. Mutant prevention concentration (MPC) of each single and combined was carried out by agar plates dilution method.Then mutant selection window(MSW) could be caculated. Results MIC of VAN, LVX, RFP and FOM for Staphylococcus aureus strain ATCC29213 separately were 1, 0.125, 0.008, 2ug/mL; MPC of these four antibiotics alone were 64, 2, >32, 64 μg/mL; and MSW(MPC/MIC) of each antibiotic were 64, 16, >4000, 32; after combinated MPC(μg/mL) of each alone were decreased as fllows: VAN+LVX (MPCNVA-4 , MPCLVX-0.125), VAN+RFP(MPCNVA-4, MPCRFP -0.008), VAN+FOM(MPCNVA -1, MPCFOM -2 ). MPCNVA of VAN combined with LVX can decreaseto 1/16 times of VAN used alone. MPCNVA of VAN combined with RFP can decrease to 1/16 times of it used alone either. MPCNVA of VAN combined with FOM can decrease to 1/64 times of it used alone. Conclusion Compared with each one alone, the combination of VAN separately with other three antibiotics can obviously decrease MPCVAN. The combination of VAN and FOM was more evidently in dropping MPCNVA of Staphylococcus aureus strain ATCC29213 and narrowing MSW of VAN.
    • 摘要：目的 評價卡泊芬凈治療中心靜脈導管相關性真菌敗血癥患者的療效和安全性.方法 采用回顧性分析2007年1月至2010年12月我院ICU病房26例中心靜脈導管相關性真菌敗血癥患者應用卡泊芬凈治療的臨床資料.結果 26例患者中,痊愈7例(26.9％),顯效12例(46.2％),總有效率為73.1％,真菌清除率為61.1％,不良反應少,所有患者均耐受治療.結論 卡泊芬凈治療中心靜脈導管相關性真菌敗血癥安全、有效.
    • 摘要：目的 構建絳紅色小單孢菌(Micromonospora purpurea)的接合轉移體系,并對該體系進行優化.方法 以絳紅色小單孢菌G1008染色體DNA為模板,經PCR擴增甲基化酶基因gntK的上下游序列各2000bp左右作為同源交換臂,并將紅霉素抗性基因作為篩選標記插入兩交換臂之間.以溫敏型質粒pKC 1139作為基本載體,構建重組質粒pFD306.借助接合轉移技術,將該質粒導入絳紅色小單孢菌G1008.結果 經抗性篩選,得到一株陽性菌株,命名為GK1008,經PCR鑒定和測序,驗證了重組質粒已整合到染色體上.GK1008菌株對紅霉素和安普霉素的抗性均超過500μg/mL.結論 絳紅色小單孢菌接合轉移體系的構建達到了預期目的,并實現了對該體系的優化,這為其它小單孢菌的分子遺傳學操作提供了借鑒.%Objective To construction the conjugal transfer system of M. Purpurea, and optimize it. Methods Two exchange arms, which were respectively located upstream and downstream of C-methyltransferase gene gntK, were amplified by PCR from M. Purpurea G1008 genomic DNA. Erythromycin resistance gene (ermE, used as screening mark) were then inserted into the arms, and the recombinant plasmid pFD306, containing the arms and ermE, for homologous recombination were constructed from thermal sensitive plasmid pKC1139. The plasmid pFD306 was then transformed into M. Purpurea G1008 by conjugation. Results One positive transformant was selected from the plate with erythromycin, which was named GK1008. After PCR identification and sequencing, it was confirmed that pFD306 was integrated into the chromosome of G1008. The resistant ability of the mutant strain to erythromycin and apramycin were all more than 500ug/mL. Conclusion Both the construction of the conjugal transfer system for M. Purpurea and the optimization of the system reached the expected purpose, which provide a reference for genetic manipulation of the other Micromonospora.
    • 摘要：Objective Response surface methodology was applied to study the decolorization of activated carbon for doramectin in fermentation broth of Streptomyces avermitilis. The aim was not only to simplify further extraction process but also to increase the quality of final product. Methods Based on decoloring rate by the detection of UV and loss of doramectin detected by HPLC, effect of activatied carbon to decoloration was investigated. The levels of factors were determined by single-factor experiments, and then optimal conditions were carried out by response surface methodology with additive amount of activated carbon, temperature and Ph. Results The decoloring time was 40 min which was determined by the single-factor experiments. The optimal technical conditions were as follows: 1.0% activated caxhor(WIV), temperature 33°C and decoloration Ph of 3. Under the optimal conditions, the decoloring rate was above 68.78% in further verified experiment and the difference was not significant with predicted value of 70.35%. Conclusion The method was effective, simple and reliable, also warranted for the commercial process.%目的 研究多拉菌素發酵提取液的脫色工藝,簡化后續提取過程及提高多拉菌素成品的質量.方法 用UV檢測發酵液的脫色率,以HPLC檢測多拉菌素的損失率,以脫色率和損失率考察活性炭對多拉菌素發酵提取液的脫色效果.先以單因素實驗確定因素水平范圍,然后再以響應面法優化脫色工藝參數(添加量,脫色溫度及溶液pH).結果 在單因素實驗基礎上,確定脫色時間為40min后,通過響應面方法對其它脫色工藝參數加以優化,得到最佳工藝條件為:活性炭的添加量1.0％(W/V)、溫度33℃、pH3,該條件下多拉菌素發酵提取液的脫色率為70.35％.驗證試驗中脫色率達到68.78％,無顯著差異.結論 該脫色工藝簡單可靠,脫色效果好,適合于工業化生產.
    • 摘要：Objective To investigate the antibiotic resistance and 16S rRNA methylase gene of the multidrug-resistant Acinetobacter baumannii (ABA) and discuss the mechanism. Methods The samples of 20 ABA isolates were collected from hospital. K-B method was used to determine the sensitivity to 5 antibacterials including kanamycin, amikacin, tobramycin, gentamicin and netilmicin, and the 16S rRNA methylase genes were analyzed by polymerase chain reaction (PCR). Results 19 strains of ABA were resistance to 5 antibacterials, while one strain was sensitive to amikacin, and showed moderate resistance to the other 4 antibacterials. Genetic testing showed the positive rate of armA was 90%, and the variation of armA was also detected, however, all isolates were negative for rmtA, rmtB, rmtC and rmtD genes. Conclusion The antibiotics resistance of Acinetobacter baumannii is very serious, and the armA gene would be the main causes of high drug-resistantce to aminoglycosides in this research and one mutant armA sequence was detected.%目的 了解臨床分離鮑曼不動桿菌(ABA)氨基糖苷類藥物耐藥性與16S rRNA甲基化酶基因存在的關系,探討多藥耐藥機制.方法 收集臨床標本20株鮑曼不動桿菌,采用K-B法測定細菌對卡那霉素、阿米卡星、妥布霉素、慶大霉素、奈替米星的敏感性;采用PCR法檢測armA、rmtA、rmtB、rmtC和rmtD 5種16S rRNA甲基化酶基因.結果 19株鮑曼不動桿菌對上述5種氨基糖苷類藥物全部耐藥,1株對阿米卡星敏感,對另外4種表現為中度耐藥.基因檢測顯示armA陽性率為90％,且armA基因存在變異,未檢測到rmtA、rmtB、rmtC和rmtD基因.結論 鮑曼不動桿菌對氨基糖苷類藥物耐藥情況嚴重,16S rRNA甲基化酶基因armA為本次臨床分離菌株耐藥的主要原因,且armA基因存在變異.
    • 摘要：目的 建立注射用頭孢美唑鈉有關物質的測定方法.方法 采用反相-HPLC方法,色譜柱為XBridge Shield RP18柱(250mm×4.6mm,5μm);流動相為0.05mol/L醋酸銨溶液(用冰醋酸調節pH值至4.5)-甲醇(80:20);檢測波長254nm;流速為0.8mL/min;柱溫:25℃.結果 在該色譜條件下,已知雜質5-巰基-1-甲基四氮唑與其它雜質、各雜質峰與主峰之間的分離均良好,頭孢美唑鈉和5-巰基-1-甲基四氮唑的檢測限均為2ng,在o.5～50μg/mL的濃度范圍內,頭孢美唑鈉和5-巰基-1-甲基四氮唑的線性均良好,r分別為0.9999和0.9999.結論 該方法操作簡便,結果準確、靈敏,可用于注射用頭孢美唑鈉中包括特異雜質5-巰基-1-甲基四氮唑在內的有關物質的測定.%Objective To establish an HPLC method to determine the related substances in cefinetazole sodium for injection. Methods The Xbridge Shield RP18 column (size: 250mmx4.6mm, 5um) was maintained at 25"C. A mobile phase containing 0.05mol/L ammonium acetate (Ph4.5, adjusted with glacial acetic acid)-methanol(80: 20) was used at a flow rate of 0.8mL/min; the detection wavelength was set at 25nm. Results Under the described condition, cefmetazole, the specified impurity 5-mercapto-l-methyl-Lh-tetrazole and other impurities can be separated well from each other The detection limits of cefmetazole and 5-mercapto-l-methyl-Lh-tetrazole were 2ng, respectively. Good linearities were obtained for cefmetazole and 5-mercapto-l-methyl-Lh-tetrazole in the range of 0.5~50ng/Ml, 0=0.9999 and 0.9999, respectively). Conclusion This method is simple, accurate, sensitive and can be used for assay and determination of related substances in cefmetazole sodium for injection, including the specificied impurity 5- mercapto-1 -methyl-1 H-tetrazole.
    • 摘要：Objective To investigate the distribution and resistance of pathogenic bacteria isolated from the blood culture specimens collected form Jan 2009 to Dec 2010. Methods A total of 3,731 blood samples were culture by BacT/ Alert 3D240, using Vitek 2 Compact for identification and drug sensitivity analysis. Results 276 stains were isolated from 275 patients, the isolates included Gram-negative baceria(62.9%), Gram-positive baceria (32.4), and fungi (5.09%). Escherichia coli is the main pathogen (88,32.0%). Most of the pathogens were isolated in the ICU (55,20.0%), followed by tumors in hematology department (42, 15.3%); surgical infections was most happen in the urology department 14, 5.09%); Gram-negative bacilli to imipenem and amikacin, laxilin/tazobactam is more sensitive. Staphylococcus to vancomycin, rifampicin, moxifloxacin and 1-ofloxacin is more sensitive. Conclusion The results of blood cultures can provide a basis for clinical antimicrobial treatment, and it is significant for hospital infection and to improve cure rates.%目的 了解醫院2009年1月至2010年12月血培養病原菌菌群分布及常見致病菌的耐藥情況.方法 血液標本在BacT/Alert 3D240全自動培養儀中培養,采用Vitek 2 Compact全自動鑒定藥敏分析系統作鑒定及藥敏分析.結果 275例血培養陽性患者共分離出細菌276株,其中革蘭陰性菌173株,占62.9％,革蘭陽性菌89株,占32.4％,真菌14株,占5.09％,感染率最高的細菌是大腸埃希菌88株,占32.0％.血液感染中ICU最高,55株,占20.0％,其次為腫瘤血液科,42株,15.3％;外科感染中最高的為泌尿外科,14株,5.09％;陰性桿菌對亞胺培南、阿米卡星、派拉西林/三唑巴坦較為敏感.葡萄球菌對萬古霉素、利福平、莫西沙星和左旋氧氟沙星較敏感.結論 及時了解血培養結果可以對臨床抗菌治療提供依據,提高治愈率,對控制醫院感染具有重要意義.
    • 摘要：Objective To evaluate the genotoxicity of tenofovir dipivoxil fiimarate (TDF) and provide the theory basis for its clinical medication. Methods Salmonella reversion test (Ames test), chromosomal aberration test of CHL cells and mouse marrow micronucleus assay were used to investigate the genotoxicity of TDF. Results Various dosages of TDF showed no mutagenic effects on salmonel latyphimurium in the Ames test, no chromosomal aberration effects were observed after CHL cells exposed to various dosages of TDF with or without rat liver supernatant 9 (S9) and TDF did not have inductive effects on formation of polychromatic erythrocyte micronucleus in mouse bone marrow micronucleus test. Conclusion TDF has no genotoxicity based on the Ames test, CHL chromosomal aberration test and micronucleus assay in the experimental conditions.%目的 分析2007-2009年安徽省臨床分離痰標本中革蘭陰性菌對抗菌藥物耐藥性變遷情況.方法 采用2009年美國CLSI推薦的瓊脂對倍稀釋法進行抗菌藥物敏感實驗,計算抗菌藥物的耐藥率、敏感率和中介率,結果采用SPSS11.5軟件進行統計分析.結果 2007年1月至2009年12月從臨床送檢的痰標本中分離出革蘭陰性菌1492株.來自ICU的不動桿菌對亞胺培南及美羅培南的敏感率分別為70.0％和61.3％,其對哌拉西林/三唑巴坦、頭孢吡肟、頭孢他啶、頭孢曲松、慶大霉素、阿米卡星和環丙沙星的耐藥率均高于非ICU菌株.來自ICU與非ICU的銅綠假單胞菌對亞胺培南、美羅培南、阿米卡星、頭孢他啶的敏感率均在50％以上.來自ICU的銅綠假單胞菌對亞胺培南、美羅培南和慶大霉素的耐藥率均高于非ICU菌株.肺炎克雷伯菌對哌拉西林/三唑巴坦、亞胺培南、美羅培南、阿米卡星的耐藥率低于30％.大腸埃希菌對哌拉西林/三唑巴坦、亞胺培南、美羅培南、阿米卡星的耐藥率在30％以下,對氨芐西林、頭孢曲松、氨曲南、慶大霉素、氟喹諾酮類的耐藥率大于50％.結論 定期進行耐藥性監測有助于了解我省細菌耐藥性變遷,為臨床經驗用藥提供依據.
    • 摘要：Objective To isolate endophytic fungi from Boletus sp., KL-1, and investigate the bioactivity of the endophytic ftingi. Methods The endophytic fungi from Boletus sp., KL-1 was isolated by tissue culture. The fungal endophytes were identified based on morphological characteristics and ITS sequence analysis. Antibacterial activities of fermentation supernatant were performed using Staphylococcus aureus, Escherichia coll, Bacillus subtilis as the target bacteria, and growth inhibition of fermentation supernatant for bean sprouts were performed. Results The endophytic strains, L-3 and L-5, obtained shared ITS sequence homology of 99% and 100% with Hypomyces chrysospermus and Mucor sp., respectively. Their morphology characteristics were consistent with Hypomyces chrysospermus and Mucor sp. Conclusion They were classified into Hypomyces chrysospermus and Mucor sp., respectively. Fermentation supernatants inhibited the growth of 5. Aureus, B. Subtilis and bean sprouts.%目的 從牛肝菌中分離內生真菌,并對其活性進行初步研究.方法 采用組織培養法從秦巴山區牛肝菌子實體中分離內生真菌,基于形態特征及ITS系統發育分析對內生真菌進行鑒定,以金黃色葡萄球菌、大腸埃希菌、枯草芽孢桿菌為指示菌,檢測內生真菌發酵產物的抑菌活性,并對其綠豆芽的抑制活性進行了研究.結果 分離獲得2株內生真菌L3和L5,L3和黃瘤孢菌(Hypompces chrysosperums)序列同源性為99％;L5和毛霉屬序列同源性為100％;兩株菌的形態學特征分別與黃瘤孢菌和毛霉屬形態特征一致.結論 內生真菌L3和L5,分別鑒定為黃孢瘤菌和毛霉屬;這兩株菌發酵液對枯草芽孢桿菌和金黃色葡萄球菌具有較強的抑制作用,對綠豆芽生長均具有抑制作用.
    • 摘要：Objective To Optimize conditions of rational selection and obtain cephalosporin C high-producing strains. Methods An efficient rational selection method were designed according to the biosynthetic pathway of cephalosporin C and mechanism of metabolic regulation. After UV mutagenesis, cephalosporin C high-producing strains were screened by an agar column high-throughput method with the pressures of copper ions, malonic acid and cephalosporin C tolerance. Results The yield of cephalosporin C of the final selected strain TBC-68071 was increased 154.6% than the original strain, and the high-producinggenetic characteristics was stable. Conclusion The results showed that rational screening of Acremonium chrysogenum overcame the blindness of random screening and improved the screening more efficiently.%目的 優化推理選育條件,獲得頭孢菌素C高產菌株.方法 根據頭孢菌素C的生物合成途徑和代謝調控機制設計菌種推理選育方案,原始出發菌株經紫外誘變后,采用托盤瓊脂柱篩選法依次對銅離子、丙二酸及頭孢菌素C耐受菌株進行選育.結果 最終獲得一株頭孢菌素C高產菌株TBC-68071,其產量較原始菌株提高了154.6％,且高產特性穩定.結論 對銅離子、丙二酸及頭孢菌素C耐受的頂頭孢霉菌株可以高產頭孢菌素C,推理選育克服了隨機篩選的盲目性,提高了菌種篩選的效率.
    • 摘要：目的 采用微波法合成PLA-PEG-PLA,并以該嵌段共聚物為基質制備ASA/PLA-PEG-PLA載藥微球和ASA-Fe3O4/PLA-PEG-PLA載藥微球,考察磁性載藥微球和非磁性載藥微球的藥物緩釋性能.方法 通過傅立葉變換紅外光譜(FT-IR)、核磁(NMR)對微波法合成的PLA-PEG-PLA的微觀結構進行了表征分析.采用乳化-溶劑揮發法制備了ASA/PLA-PEG-PLA載藥微球,通過正交設計實驗優選載藥微球的最佳制備條件,在此基礎上利用單微乳法制備的Fe3O4納米粒子制備了ASA-Fe3O4/PLA-PEG-PLA載藥微球.通過透射電子顯微鏡(TEM)、X-射線衍射(XRD)對Fe3O4納米粒子進行微觀結構表征和性能分析.采用傅立葉變換紅外光譜(FT-IR),掃描電子顯微鏡(SEM)對制備的載藥微球進行了微觀結構的表征和分析.結果 微波法合成的PLA-PEG-PLA是一種三嵌段共聚物.載藥微球呈規則球形,表面光滑,粒徑分布較均勻,平均粒徑約為20μm.體外模擬釋藥試驗表明ASA/PLA-PEG-PLA載藥微球和ASA-Fe3O4/PLA-PEG-PLA載藥微球24h釋藥率分別為69.16％和100％.結論 以微波法合成的PLA-PEG-PLA作為藥物載體具有明顯的緩釋作用.ASA-Fe3O4/PLA-PEG-PLA磁性載藥微球比ASA/PLA-PEG-PLA非磁性載藥微球具有較快的藥物釋放速率.%Objective PLA-PEG-PLA was synthesized by microwave-assisted polymerization. Drag-loaded microspheres were prepared by using this copolymer as matrix.The drag release properties of the magnetic drug-loaded microsphere and non-magnetic drag-loaded microsphere were observed. Methods The microstructure of synthesized PLA-PEG-PLA was characterized by FT-IR, 'H-NMR. ASA/PLA-PEG-PLA drag-loaded microspheres were prepared by emulsion-solvent evaporation method. The optimum experimental conditions of drag-loaded microspheres were screened by orthogonal experiment. Magnetic ferroferric oxide(Fe3O4) was prepared by water-in-oil microemulsion processing and characterized by TEM and XRD. The microstructure of drag-loaded microspheres was characterized and analyzed by FT-IR, SEM. Results The polymer was synthesized by microwave-assisted method was a ABA type copolymer(PLA-PEG-PLA). The drag-loaded microspheres were of regular sphere and smoothly surface. Their distribution were even and the average diameter was 20um.The drag release of two kinds of drag-loaded microspheres were studied by in-vitro release method. The drag cumulative release ratio of ASA/PLA-PEG-PLA microspheres and ASA-Fe3O4/PLA-PEG-PLA magnetic microspheres were 69.16% and 100%, respectly.Conclusion The PLA-PEG-PLA which was synthesized by microwave-assisted polymerization as a drug carrier has obvious sustained-release property. The drug release rate of ASA-Fe3O4/ PLA-PEG-PLA magnetic drug-loaded microsphere is bigger than that of ASA/PLA-PEG-PLA non-magnetic drug-loaded microsphere.
    • 摘要：Objective To evaluate the genotoxicity of tenofovir dipivoxil fiimarate (TDF) and provide the theory basis for its clinical medication. Methods Salmonella reversion test (Ames test), chromosomal aberration test of CHL cells and mouse marrow micronucleus assay were used to investigate the genotoxicity of TDF. Results Various dosages of TDF showed no mutagenic effects on salmonel latyphimurium in the Ames test, no chromosomal aberration effects were observed after CHL cells exposed to various dosages of TDF with or without rat liver supernatant 9 (S9) and TDF did not have inductive effects on formation of polychromatic erythrocyte micronucleus in mouse bone marrow micronucleus test. Conclusion TDF has no genotoxicity based on the Ames test, CHL chromosomal aberration test and micronucleus assay in the experimental conditions.%目的 檢測富馬酸泰諾福韋雙特戊酯(TDF)的遺傳毒性,為臨床用藥提供理論依據.方法 應用鼠傷寒沙門細菌回復突變試驗(Ames試驗)、體外培養中國倉鼠肺成纖維細胞(CHL)細胞染色體畸變試驗和小鼠骨髓微核試驗檢測該藥物的遺傳毒性.結果 該藥物對鼠傷寒沙門菌無致突變性,對體外培養CHL細胞染色體無致畸變作用,對昆明小鼠無誘發骨髓嗜多染紅細胞微核的效應,三個試驗結果均呈陰性.結論 TDF不具有遺傳毒性.
    • 摘要：The most important mechanism of resistance to P-lactam antibiotics is the P-lactamases produced by Enterobacter cloacae, and the P-lactamases is different in catology and character and produce a new ones under Enterobacter cloacae that contain p-lactamases encounter simultaneous or consecutive selective pressure with different P-lactamases molecules. This review describes evolution and characteristics of the P-lactamases produce by Enterobacter cloacae.%陰溝腸桿菌產β-內酰胺酶是對β-內酰胺類抗生素耐藥的主要機制,所產β-內酰胺酶種類較多、特性各異,并在β-內酰胺類抗生素廣泛應用的選擇壓力下,不斷有新的β-內酰胺酶產生.文中對陰溝腸桿菌產β-內酰胺酶(EsBLs、AmpC、碳青霉烯酶)耐藥性的研究進展作了簡要綜述.
    • 摘要：目的 合成凡德他尼(vandetanib)并改進其合成工藝.方法 以N-Boc-4-哌啶甲醇為起始原料,經磺化、縮合、N-甲基化、硝化、還原、環合、氯化、胺化反應制得凡德他尼.結果 所得產物經元素分析、核磁共振譜及質譜等確證了結構.結論 改進后的合成路線操作簡單,收率高,易于實現工業化.%Objective To synthesize vandetanib and optimize the process. Methods Vandetanib was synthesized by steps of sulfonation,condensation, N-methylation,nitrification, reduction, cyclization, chlorination and amination. Results Chemical structure of vandetanib was conformed by element analysis, 'H-NMR and ESI-MS, etc. Conclusion A more reasonable operational path for the manufacturing process of vandetanib was provided by this experiment.
    • 摘要：In order to obtain mutants with higher antibiotics yield, the germinating spores of the wild strain Chaetomium cupreum CH21 were mutated by two mutagens, microwave and UV, and screened by PDA double-plate and bioassay both using Colletotrichum capsici as indicator. The optimal mutagen dosages were determined: 500W 2450MHz under microwave irradiation for 15s, and 15W, 30cm under ultraviolet ray irradiation for 300s. CH21, the diameter of inhibiting ring of which was 12.50mm, was mutated by microwave and UV each for once. Five mutants with high yield of antibiotics were isolated. The diameter of inhibiting ring of CH21-2-20 was 20.20 mm, which was the largest and increased by 62% in comparison to CH21. Cultivated for five continuous generations, the diameter of inhibiting ring of CH21-2-20 stabilized between 19.40 mm and 20.38 mm.%以角毛殼菌(Chaetomium cupreum)CH21的萌發孢子作為誘變材料,采用微波輻照和紫外線照射進行誘變處理,用辣椒炭疽菌(Colletotrichum capsici)作為測試菌株,結合PDA雙層平板法初篩和管碟法復篩,選育高產抗生素的突變株.結果表明:最佳微波誘變條件為500W、2450MHz、15s,紫外誘變條件為15W、30cm、300s.對出發菌株CH21進行一輪微波誘變和一輪紫外誘變,篩選得到5株高產菌株,其中CH21-2-20抑菌圈直徑最大,為20.20mm,較抑菌圈直徑為12.50mm的出發菌株增大了62％.連續傳代5次,CH21-2-20抑菌圈直徑穩定在19.40～20.38mm.

      中國抗生素雜志的期刊信息

      • 曾用名：抗生素
      • 創刊時間：1976
      • 地區：CN
      • 語言：中文
      • 熱門主題：中國醫藥集團總公司四川抗菌素工業研究所;中國醫學科學院醫藥生物技術研究所
      • 學科分類： 藥學;

        Pharmacology, Toxicology and Pharmaceutics:Pharmacology;

      中國抗生素雜志的獲獎情況

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      中國抗生素雜志的投稿信息

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