中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

轴向载荷分担比指导外固定器动力化的临床应用

目的:探讨轴向载荷分担比用于胫腓骨骨干骨折术后指导外固定器轴向动力化促进骨折愈合的有效性。方法:选取外固定器治疗的胫腓骨骨干骨折患者100例,随机分为观察组50例,对照组50例。观察组在轴向载荷分担比指导下行外固定器轴向动力化治疗,对照组未行动力化,随访比较两组的治疗效果。结果:所有患者均获随访,随访时间4～12个月,平均6.5个月,治疗期间所有患者均未出现外固定针断裂、松动及再骨折等并发症,观察组1例骨搬移患者轴向载荷分担比5%,X线片显示骨折断端有连续性骨痂通过,拆除外固定器连接杆后发生移位,恢复原数值行轴向加压再动力化,现已愈合。观察组除外1例骨搬移患者,其余49例患者外固定器固定时间为[(24.4±4.7)周],骨折临床愈合时间为[(22.4±4.7)周],与对照组50例患者外固定器固定时间[(29.3±5.6)周],骨折临床愈合时间[(27.3±5.6)周]比较,显著减少(P0.05)。结论:外固定器轴向载荷分担比指导胫腓骨骨干骨折外固定术后轴向动力化可以加速骨折愈合,但不适合骨搬移截骨端已硬化患者。     

益母草中阿魏酸对含益母草中成药质量标准影响的探讨

目的：建立HPLC/TQ-MS测定益母草中阿魏酸含量的方法并测定不同产地益母草中阿魏酸含量，评价益母草中阿魏酸对中成药调经止痛片及新生化颗粒的质量影响，为制定含有益母草并以阿魏酸为定量指标的中成药质量标准提供参考。方法：采用薄层色谱法及UPLC-Q/TOF定性鉴别及分析益母草中阿魏酸，采用HPLC/TQ-MS定量分析10批不同产地益母草中阿魏酸含量。基于定量分析结果及处方用量探讨益母草中阿魏酸含量对其中成药质量标准的影响。结果：薄层鉴别及UPLC-Q/TOF定性分析结果显示，10批不同产地益母草中均含有阿魏酸。HPLC/TQ-MS定量分析结果显示，益母草中阿魏酸含量在0.004 2%~0.006 5%之间。结论：益母草与当归、川芎等含有阿魏酸的药材配伍且其用量较大时，益母草中阿魏酸含量会对其质量评价产生一定的影响。     

腹膜转移瘤的影像学诊断

目的探讨腹膜转移瘤的影像学表现特点。方法回顾性分析经手术及穿刺活检证实的35例腹膜转移瘤的影像学表现,并与手术结果对照,35例做CT平扫及增强扫描,5例行MR I检查。结果(1)腹膜转移瘤常表现为大量腹水(22/35);(2)腹膜结节状增厚(23/35);(3)大网膜饼形增厚(16/35)和大网膜污垢样改变(12/35);(4)肠系膜污垢样改变(12/35)及结节状改变(9/35);(5)腹腔单发或多发囊性改变,有占位效应(4/35)。结论CT/MR I是发现腹膜转移灶的重要影像学方法。     

奥美定注入小香猪体内后生殖毒性的观察

目的　观察奥美定注入小香猪体内后的生殖毒性。方法　注入奥美定后观察小香猪母代及子代的生长、健康情况 ,抽出奥美定检测丙烯酰胺单体含量以及抽血查染色体及微核试验观察。结果　 6只母代小香猪健康 ,2只与公猪交配 ,4个月及 5个月后生出 9只及 4只子代小猪 ,健康情况亦良好。在半年及 1年后分别抽出奥美定检测丙烯酰胺单体没有增加 ,共检测 9只小香猪的染色体包括母代及子代 ,均未发现数目畸变及结构畸变 ,微核试验有细微的变化 ,并初步反映出与用药量大小呈正相关 ,但超量注射的一只动物 (18.5ml/kg)变化的千分值仍在正常范围内。结论　从目前几项观察与检测指标看 ,实验量奥美定注入小香猪体内尚不具生殖遗传毒性     

Immunogenicity study of low-dose administration of hepatitis B virus vaccine in newborn infants: A cost reduction trial

Different doses of hepatitis B virus vaccine—prepared by Korea Green Cross Corporation, were given to healthy infants born to HBsAg-negative mothers at birth, 1 and 6 months of age. A dose of 2 μg was administered intradermally in Group A and, in the three other groups, the vaccine was given intramuscularly (i.m.). An adequate follow-up observation was possible for 9 months after birth in 22, 25, 23 and 21 infants in Groups A, B, C and D, respecvely.
Group C (5 μg, i.m.) produced seroconversion most rapidly, showing the highest rate (96%) at 9 months of age. The lowest seroconversion rate (5%) was found at the age of 1 month in Group A subjects, but the rate increased to 91% after a booster dose was given at 6 months of age.
While it can be concluded that a 5 μg i.m. dose of vaccine at 0, 1 and 6 months of age is optimum for the immunization of infants in efficacy and economy, a 2 μg intradermal dose can also be considered as an immunogenic and economical regimen, though the immune response is slower and a special technique is required for immunization.     

放射治疗71例骨转移癌止痛效果分析

目的观察低于常规剂量的2种分割方式治疗骨转移性疼痛的疗效。方法71例恶性肿瘤晚期骨转移患者,总计93处骨转移灶,根据疼痛程度及行动受限程度,采取2种均低于常规剂量的分割方式进行放射治疗,分别为Dm30Gy/10f/2W,Dm30Gy/6f/2W。观察疼痛缓解情况。结果2种分割方式止痛有效率分别为88%、95%。两组间无显著差异性(P>0.05)。与国内多数文献报告的结果接近。结论低于常规剂量的分割方式对转移性骨痛疗效与常规剂量的分割方式的疗效相当,且简便易行。     

重型病毒性肝炎合并急性胰腺炎的临床分析

目的通过对重型病毒性肝炎合并急性胰腺炎的病例进行分析,以找出其临床特点.方法对上述病例的临床症状、实验室检查、治疗情况、病情的发生发展及预后进行分析.结果少数患者表现不典型或胰腺炎的症状被重型肝炎的严重症状所掩盖,容易发生漏诊及误诊;且病情发展快、预后差.结论只有对相应患者尽早做血、尿淀粉酶的测定并反复复查,才能做到及时诊断和治疗.     

超声心动图对62例房间隔缺损封堵术后心功能变化的评价

目的：应用超声心动图评价房间隔缺损(ASD)封堵术前后左、右心室功能的变化。方法：对62例成功施行经皮穿刺ASD封堵术的患者进行研究。所有患者在术前、术后1周及1个月分别进行超声心动图检查．观察心脏大小及功能的改变。结果：ASD封堵术后，左室舒张末期前后径、左室舒张末期容积、左室每搏量及左室射血分数增大，而左室收缩末期容积未见明显改变；右室舒张末期前后径、右室舒张末期容积、右室收缩末期容积、右室每搏量、右室射血分数及右室心肌工作指数均减小。结论：经皮穿刺ASD封堵治疗既可减轻右室容量负荷，改善右室功能，也可改善左室的收缩功能：超声心动图对ASD封堵前后心脏血流动力学评价及疗效的观察起了重要的作用。     

Differentiation of human epidermal stem cells into fibroblasts induced by TGF-β1 in vitro

Objective To investigate the correlation between human epidermal stem cell (hESCs) and hypertrophic scar or keloid. Methods Improved collagen Ⅳ-coated adhesion methods was used to isolate and culture the epidermal stem cells after neutral protease selectively digested the dermo-epidermal junctions. After the cells were cultured and expanded in vitro, and passage 3 hESCs were induced by different concentrations of TGF-β1 (0.1, 5.0, and 10.0 ng/ml). Morphological fea-tures and identification of these cells were meseasured by HE, Masson, immunohistochemical staining on the days 3 and 7, respectively. Results After induced by TGF-β1 for 3 and 7 days, the morpholo-gy of the epidermal stem cell (hESCs) was changed into fusiform shape, similar to fibroblasts. 70 % ofthe cell which was induced by TGF-β1 were blue stained in the cytoplasm by Masson stain, which is the distinctive method for collagen, suggesting collagen appeared or increased in the cells. The collagen concentrations in supernatants of hESCs were 0.4150±0.0014, 0.3380±0. 0020, and 0.3870±0.0020, much higher than that in control group (0.0780±0.0025) and normal skin fibro-blast group (0.15004±0.0051) (P<0.05). Immunohistochemical staining revealed that positive rates of these cells for anti-vimentin staining were more than (95.00±1.20)% in experiments and (5.70±0.20)% in control group. Conclusion The differentiantion of hESCs induced by TGF-β1 into fibro-blasts indicates that hESCs may play a role in the pathogenesis of hypetrophic scar and keloid.