口服胰岛素纳米脂质体的制备及其降血糖作用

目的改进胰岛素纳米脂质体的制备方法,考察脂质体经正常大鼠小肠给药和灌胃给药的降血糖效果。方法通过改变油相容积及油/水相比例,采用逆相蒸发-超声法制备了胰岛素纳米脂质体;测定了纳米脂质体的包封率;通过灌胃和小肠途径,给正常大鼠以350IU/kg的剂量,用酶-苯酚法测定大鼠血糖,并与空白纳米脂质体、胰岛素溶液及生理盐水相比较。结果胰岛素纳米脂质体的平均粒径为83.3nm,多分散系数为0.445,包封率为78.5%;大鼠灌胃给药后未能显示降血糖作用,但小肠给药后0.25h血糖下降37.6%±13.9%,0.5h血糖下降了89.3%±9.5%,维持50%左右降血糖水平2h,而同法给予的胰岛素溶液、生理盐水和空白纳米脂质体组均无降血糖作用。结论实验初步证实制备的纳米脂质体可以保护胰岛素在小肠中的活性并促进胰岛素吸收。     

口服胰岛素肠溶聚合物脂质杂化纳米粒的制备与评价

为了提高胰岛素的口服生物利用度,本研究以聚乙二醇聚乳酸共聚物(PEG-PLA)为高分子载体材料、磷脂s75为脂质材料、Eudragit L100为肠溶材料制备口服胰岛素肠溶聚合物脂质杂化纳米粒(INS-NPs L100),并对其体内外性能进行评价。采用W/O/W复乳溶剂挥发法制备胰岛素聚合物脂质杂化纳米粒(INS-NPs),以包封率、粒径和释药行为为评价指标,采用单因素法对处方进行优化;将最优INS-NPs与肠溶材料Eudragit^® L100混合制备成INS-NPs L100,并对其形态、体外释放及健康大鼠灌胃后的降血糖作用进行评价。以最优处方制备的INS-NPs包封率为(62.18±4.51)%,平均粒径为(225.2±94.3)nm,多分散系数为0.191±0.068,Zeta电位为-(14.84±1.26)mV。包裹肠溶材料后所制备的INS-NPs L100,在pH 1.0盐酸溶液中2 h累积释放量为8.01%,在pH 6.8的磷酸盐缓冲液中6 h累积释放量为67.31%。将所制备的INS-NPs L100经口给予健康大鼠(38 IU/kg)后,具有明显的持续降血糖作用,3.5 h时血糖浓度可降至初始值的76%。实验结果表明,本研究所制备的INS-NPs L100可有效减缓胰岛素在胃液中的释放速度,提高蛋白在胃肠道中的稳定性,为多肽、蛋白类药物口服给药提供了新的研究思路。     

胰岛素/维生素B12-透明质酸纳米粒的制备及口服给药体内外性质的评价

[目的]维生素B12修饰的透明质酸纳米粒口服递送胰岛素的体内外性质评价.[方法]采用二次乳化法制备载胰岛素/维生素B12修饰透明质酸纳米粒(INS/VB12-HA NP),激光粒度分析仪测定纳米粒粒径和分布,反相高效液相法测定纳米粒包封率和载药量;并用人结肠腺癌细胞(Caco-2)单层膜模型体外评价INS/VB12-HA NP的细胞摄取与跨膜转运;以糖尿病模型大鼠降血糖实验评价口服INS/VB12-HA NP的药效.[结果]所制备的INS/VB12-HA NP粒径在185 ～286 nm之间,PDI小于0.25,包封率在55％左右.细胞摄取实验表明在25～ 200 μg/mL胰岛素浓度范围内和孵育0.5 h后Caco-2细胞对INS/VB12-HA NP的摄取量显著高于胰岛素溶液组.Caco-2细胞单层膜跨膜转运实验中,4h内跨膜电阻没有明显变化,VB12-HA NP组比对照溶液组有更多的胰岛素跨膜量和更快的跨膜速率.糖尿病大鼠的降糖实验显示,与口服胰岛素溶液相比,纳米粒组均有显著的口服降血糖作用.[结论]VB12修饰的透明质酸纳米粒可促进胰岛素跨过Caco-2细胞单层膜,且对糖尿病大鼠的口服降糖作用优于胰岛素溶液.     

麦胚凝集素修饰的EGCG-明胶-壳聚糖纳米粒的制备、表征及体外抗肿瘤活性研究

目的?制备麦胚凝集素（WGA）修饰的表没食子儿茶素没食子酸酯（EGCG）-明胶(Gel)-壳聚糖(Cs)纳米粒,研究其对结肠癌HT-29细胞的作用。方法?以明胶及壳聚糖为载体辅料,采用静电自组装的方法制备EGCG-Gel-Cs纳米粒,以包封率为指标,通过Box-Behnken设计-效应面法（BBD-RSM）优化纳米粒的制备处方及工艺,再将经戊二醛活化的WGA修饰到纳米粒表面。采用差示扫描量热分析药物在纳米粒中的存在状态,采用细胞毒性及细胞凋亡实验,比较研究纳米粒与原料药的体外抗肿瘤活性。结果?EGCG-Gel-Cs纳米粒的最优处方:Gel与Cs的质量比为4.2,Gel与EGCG的质量比为2.82,反应温度为34℃,包封率为(74.42±0.074)%。EGCG-Gel-Cs纳米粒粒径为(264.13±6.48)nm,经过修饰后纳米粒粒径为(389.70±9.00)nm。WGA-EGCG-Gel-Cs纳米粒对HT-29细胞的细胞毒性和细胞凋亡率显著高于EGCG原料药。结论?WGA-EGCG-Gel-Cs纳米粒可显著提高细胞毒性作用。      

姜黄素固体脂质纳米粒制备及体外释放的研究

[目的]以单硬脂酸甘油酯为载体材料制备姜黄素固体脂质纳米粒及其体外释放行为的研究。[方法]采用乳化蒸发-低温固化法制备姜黄素固体脂质纳米粒,高速离心法测其包封率,激光粒径仪测定其粒径、电位,用差示扫描量热仪(DSC)表征其性质,采用透析法考察固体脂质纳米粒中姜黄素的体外释放行为。[结果]姜黄素固体脂质纳米粒的平均粒径为(89.24±2.06)nm,Zeta电位为(-18.77±1.27)m V,药物平均包封率为(89.55±1.84)%,DSC结果表明其理化性质稳定可靠,体外12 h累计释放率为(43.12±1.02)%。[结论]制备的姜黄素固体脂质纳米粒粒径小且分布均匀,具有良好的缓释作用。     

胰岛素纳米粒对大鼠实验性糖尿病的降血糖作用

目的　制备氰基丙烯酸正丁酯胰岛素纳米粒 (insulinnanoparticles INP) ,研究其理化特性 ,观察 sc和 po给药对糖尿病大鼠的降血糖作用 .方法　用改良的乳液聚合法制备氰基丙烯酸正丁酯胰岛素纳米粒 ,用透射电子显微镜观察 INP的大小、形态 ,用高压液相色谱法 (HPL C)测定其包裹率 ,用 ip四氧嘧啶制备糖尿病大鼠模型 .血糖用快速血糖仪测定 .用 t检验和 χ2 检验进行统计学处理 .结果　用改良的乳液聚合法制得的 INP粒径为 (30± 0 .5 ) nm,包裹率为 95 % ,给糖尿病大鼠 sc30 U·kg- 1 ,INP组 1h开始起作用 ,4～ 6 h达峰值 ,血糖降低 98% ,作用持续 2 4h,而普通胰岛素组 1h达峰值 ,最大降血糖幅度为 5 5 % ,作用持续 4h. sc 2 0 U· kg- 1 ,INP组1h开始起作用 ,4～ 6 h达峰值 ,最大降血糖幅度为 74% ,作用持续 2 0 h,而鱼精蛋白锌胰岛素组 1h开始起作用 ,4～ 6 h达峰值 ,最大降血糖幅度为 41% ,作用也持续 2 0 h.给糖尿病大鼠 po INP 12 0 U· kg- 1 ,1d后空腹血糖开始下降 ,3d效果最佳 ,血糖降低 89% ,5～ 7d后恢复高血糖 ,而 po普通胰岛素组血糖无明显变化 ,2～ 4d的血糖两组比较相差显著 (P<0 .0 5 ) . 5 0 U· kg- 1 组及 10 0 U· kg- 1 组作用持续时间均为 5d,12 0 U· kg- 1 组的作用时间为 7d.三     

口服和经肠道注入胰岛素油溶液对糖尿病大鼠降糖作用的比较研究

目的比较经肠道注入与口服胰岛素油溶液两种给药方式对糖尿病大鼠的降血糖效果。方法将糖尿病大鼠分为3组,每组4只,空白组:不给药;对照组:口服50u/kg体重胰岛素油溶液;实验组:经肠道注入50u/kg体重胰岛素油溶液。分别于给药后1、2、3和4h测定动物血糖,并对结果进行统计学分析。结果空白组动物血糖无变化,口服经胃组给药后1、2、3和4h的血糖百分数分别为(84±14)%、(73±17)%、(71±8)%、(65±22)%,经肠道注入组分别为(66±15)%、(54±19)%、(46±25)%、(49±22)%,差异具有显著性(P<0.05)。结论肠道注入与口服胰岛素油溶液对糖尿病大鼠均有明显的降糖作用,肠道注入胰岛素油溶液的降血糖效果优于口服经胃给药方式。     

口服补镁对实验性老年2型糖尿病大鼠胰岛素受体表达水平的影响

目的 观察口服补镁对老年2 型糖尿病大鼠胰岛素受体表达水平的影响.方法 将老年2 型糖尿病大鼠模型分为不同剂量的口服补镁组,测定大鼠空腹血糖、血清胰岛素及胰腺和骨骼肌组织胰岛素受体表达水平.结果 高剂量补镁组(2g/kg) 胰腺中胰岛素受体表达水平(MOD 值) 由0.331±0.003 提高至0.342±0.002 ;骨骼肌组织胰岛素受体表达水平由0.345±0.003 提高至0.355±0.002,差异均有统计学意义(P<0.05).同时,高剂量补镁组空腹血糖由(16.85±0.76)mmol/L 降至(15.49±0.57)mmol/L,而血清胰岛素水平由(20.35±0.52)μIU/ml 降至(19.05±0.62)μIU/ml.结论 口服补镁可显著提高老年2 型糖尿病大鼠胰岛素受体表达水平,改善胰岛素敏感性.     

鬼臼毒素硬脂酸固体脂质纳米粒的制备

目的为提高鬼臼毒素(PPT)制剂的疗效,降低毒副作用,以硬脂酸为载体材料制备PPT固体脂质纳米粒。方法采用改良的微乳技术制备PPT固体脂质纳米粒;用透射电镜考察了纳米粒的形态;用高效液相色谱法测定PPT固体脂质纳米粒的包封率。结果PPT固体脂质纳米粒基本呈圆球状或椭圆球状,粒径为(56.5±25.8)nm,包封率85.6%。结论PPT固体脂质纳米粒包封率高,粒径分布较均匀,具有较好的稳定性,是有希望的表皮靶向制剂。     

胰岛素多肽固体脂质纳米粒的制备与理化性质研究

目的该课题选用水溶性多肽类药物,以生物相容性好的脂质为主体材料,制备固体脂质纳米粒。方法采用溶剂扩散法制备单硬脂酸甘油脂纳米粒,以胰岛素(ISULIN)为模型药物。研究纳米粒的理化性质,以微粒粒度与zeta电位测定仪测定其粒径分布、表面电位;高效液相法测定了药物包封率;考察载药纳米粒的体外释放特性;以4种不同比例的硬脂酸、油酸和单硬脂酸甘油脂,通过溶剂扩散法制备混合脂质纳米粒,考察混合脂质纳米粒的理化性质、包封率和体外释放特性。结果用水性溶剂扩散法可简便快速制备得到单硬脂酸甘油酷固体脂质纳米粒,纳米粒粒径呈单峰分布,体均粒径(435.3±121.6)nm,表面电位-(20.7±1.6)mV。采用HPLC测定,药物的包封率68.2%。体外释放研究结果显示,INSULIN-SLN在前8h快速释放了纳米粒所载药物的28.4%,随后每天以3.7%的速率持续释放。结论采用单硬脂酸甘油醋、硬脂酸、油酸混合脂质处方,并不显著影响纳米粒的粒径、表面电位和药物的包封率。油酸的加入,可在一定程度上增加药物的释放。     

Acupuncture Treatment of Vomiting

CASE HISTORY A female patient, 46 years old, head of the foreign affairs department of a certain university in Beijing, paid her first visit on October 9, 2006, with the chief complaint of vomiting for one month. She got vomiting after meals in early September. Before that, she had discomfortable sensation in the stomach due to angry with others, but she didn't pay much attention. Later, it developed into vomiting after eating. After the vomiting, the discomfort would be relieved, but with slight hypodynamia. She was once diagnosed as having 'neurogenic vomiting'. Having taken some western and Chinese drugs, the above symptoms were a little bit improved, but she would have nausea upon eating and with regurgitation. Because of the fear for vomiting, she did not dare to have food intake, with body weight reduction of 6 kilos in one month.     

Qiu Baoguo''''s Experience in Treating Consumptive Syndromes after Radio-Chemotherapies

Radiotherapy and chemotherapy are the important modern medical therapies for malignant tumors,yet they can also bring about serious local and systemic toxic side reactions so to decrease the patient;'s life quality,manifested by a series of consumptive symptoms.Having engaged in the combined work of Chinese and western medicine for nearly 50 years,the research fellow Qiu Baoguo in Henan Provincial Academy of TCM has developed his unique views on the TCM study of consumptive syndromes.The author of this essay had once the fortune tO follow Dr.Qiu in clinic,and specially would like to introduce in the following Dr.Qiu's experience in treating consumptive syndromes after radio-chemotherapies for patients with malignant tumor.     

Insomnia Due to Deficiency of Both the Heart and Spleen Treated by Acupuncture-Moxibustion and Chinese Tuina

OBJECTIVE: To observe therapeutic effects of the comprehensive therapy of acupuncture-moxibustion and Chinese Tuina for treatment of insomnia due to deficiency of both the heart and spleen. METHODS: 92 cases were divided randomly into the treatment group (treated by acupuncture-moxibustion and Chinese Tuina) and the control group (treated by acupuncture-moxibustion). RESULTS: The therapeutic effect of the treatment group was obviously superior to that of the control group (the CHI2 test showed P < 0.01). CONCLUSIONS: The comprehensive therapy of acupuncture-moxibustion and Chinese Tuina can give marked therapeutic effects for treatment of insomnia due to deficiency of both the heart and spleen.     

Analysis of CK-19,PDX-1,Nestin,Ngn3 in different donor islet purity in rats

Objective: To investigate if there are the CK-19, PDX-1, Nestin, Ngn3 positive cells in the donor islets of different purity in rats. Methods: Thirty male adult SD rats were randomly divided into 3 groups. Islets were isolated using digestion by ductal injection of collagenase. Group Ⅰ (n=10): Separating cell preparations were not purified, Group Ⅱ(n=10): Islet sediment was purified with 25% Ficoll400 ,Group Ⅲ (n=10): Islet sediment was purified with 25% and 11% Ficoll-400. The levels of protein of CK-19, PDX-1, Nestin and Ngn3 were detected by immunohistochemistry and the mRNA of CK-19, PDX-1, Nestin, Ngn3 was amplified by RT-PCR. Results: After two different purification methods applied, three islet preparations of different purities were obtained. The difference of islet purity was significant among various groups (P＜0.05). Compared with group Ⅱ and group Ⅲ,the protein and mRNA of CK-19, PDX-1, Nestin,Ngn3 were both higher in group Ⅰ; group Ⅲ was poorly expressed. Conclusions: The three different islet purity donor islet have different CK-19, PDX-1, Nestin, Ngn3 positive cells within them, indicating that there are some islet stem cells in the purified donor islet.     

A preliminary screening study on the associated proteins in human psoriasis vulgaris by serum proteomics technologies

Objective：To investigate the optimum screening conditions of associated proteins in human psoriasis vulgaris by serum proteomics technique, and to screen the different expression proteins related with psoriasis vulgaris. Methods：Serum samples of peripheral blood were collected from newly diagnosed psoriasis vulgaris patients in the clinic, and 20 matched healthy persons. Serum albumin IgG was removed by filtering with ProteoExtract Albumin/IgG. After comparative proteomics analysis the different protein spots were identified using 2-DE and MS. Results ：Electrophoresis figures with high resolution and reproducibility were obtained. Three different expression proteins were found only in the serum from psoriasis vulgaris patients, while nine other different proteins expressing from healthy volunteers. Conclusion：The protein expression was different in the serum between the psoriasis vulgaris patients and healthy volunteers. It was hoped that we could find the biomarkers related to psoriasis vulgaris by using proteomics.     

A CASE OF HUGE GASTRIC DISOPYROBEZOAR

PYTOBEZOARS are common bezoars in gastrontestinal tract, commonly seen in stomach and mall intestine,1but huge disopyrobezoars are     

Acupuncture Treatment of Chest Bi Syndrome

CASE HISTORY A male,a retired officer of 61 years old,paid his first visit on May 12,2006.The patient stated that 2 weeks before he suddenly got paroxysmal precordial choking pain,with irregular attacks.Each attack would last several seconds to several minutes.The attack was accompanied with heavy oppressed sensation in the precordial region,palpitation,lassitude,and in severe cases,sweating,which was once diagnosed by a hospital as'coronary heart disease'.Recalling the case history,the patient said that several days before he got angry with others because of some affairs in work,and he was not so used to the life pattern since he had just retired from his busy working post.At usual times,he was quick tempered and peevish.In recent days,he had poor appetite,and loose stool.     

Instructions to Contributors

The English edition of Chinese Journal of Integrative Medicine is edited and published by the Chinese Journal of Integrated Traditional and Western Medicine Press.Original scientific papers of advanced clinical and experimental medicine in the field of complementary/alternative medicine or integrative medicine are expected.     

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