复方祛白喷雾剂的皮肤毒性和安全性研究

目的 研究复方祛白喷雾剂的皮肤毒性和经皮肤用药的安全性。方法 采用家兔急性皮肤毒性试验、豚鼠皮肤过敏试验、家兔皮肤刺激性试验,观察复方祛白喷雾剂经皮肤用药的急性毒性、过敏性和刺激性。结果 复方祛白喷雾剂对家兔完整皮肤与破损皮肤无急性毒性反应;对豚鼠皮肤无致敏作用;对家兔破损皮肤有轻度刺激性反应,但给药48 h后该刺激性反应消失。结论 复方祛白喷雾剂无明显急性皮肤毒性,经皮肤用药的安全性良好。     

Assessment of dermal safety of oil extracted from Periplaneta americana: acute dermal toxicity,irritation, and sensitization

Abstract

Introduction

The American cockroach (Periplaneta americana) is used in traditional Chinese medicine. Periplaneta americana (P. americana) is rich in oil that has shown potential antioxidant and antibacterial activities in vitro.     

氯霉素泼尼松搽剂抗炎、抗过敏和止痒作用动物实验研究

目的：考察氯霉素泼尼松搽剂皮肤用药的安全性。方法：分别对健康家兔进行皮肤急性毒性试验、皮肤刺激性试验,对健康豚鼠进行皮肤过敏性试验。结果：氯霉素泼尼松搽剂对家兔完整皮肤、破损皮肤均无明显急性毒性和局部刺激性,对豚鼠皮肤无过敏反应。结论：氯霉素泼尼松搽剂短期皮肤用药是安全的。     

酸性成纤维细胞生长因子治疗深Ⅱ度烧伤的多中心随机对照临床试验

目的:评价重组人酸性成纤维细胞生长因子(rh-a FGF)与重组人碱性成纤维细胞生长因子(rh-b FGF)治疗深Ⅱ度烧伤的临床疗效与安全性。方法:采用多中心、随机、平行对照临床试验方法,入选5个研究中心216例深Ⅱ度烧伤患者,两组患者均给予相应抗感染、营养补充治疗。观察组(108例)入院时首先根据创面大小给予rh-a FGF1瓶/5 cm2进行冲洗,然后每日3~4喷/cm2喷雾治疗,6~8次/d,对照组(108例)给予rh-b FGF治疗,给药方法同观察组。随访30 d后,评价两组患者创面愈合情况。结果:观察组完全愈合时间、溶痂时间、12 d完全愈合率、15 d完全愈合率等指标均明显优于对照组(P<0.05)。治疗7 d后,观察组白细胞水平、渗出评分均明显低于对照组(P<0.01)。两组总评分中度构成比比较,差异有统计学意义(P<0.05)。结论:rh-a FGF治疗深Ⅱ度烧伤创面临床疗效优于rh-b FGF,安全性相似。     

复方镰形棘豆凝胶剂的皮肤安全性评价

目的:制备一种外用复方镰形棘豆凝胶剂,并对其皮肤用药的安全性进行评价。方法:选用壳聚糖为凝胶基质制备复方镰形棘豆凝胶剂;用复方镰形棘豆凝胶剂考察豚鼠皮肤致敏性、家兔皮肤刺激试验、急性毒性试验和30 d 长期毒性试验。结果:复方镰形棘豆凝胶剂对豚鼠无致敏性,对家兔完整皮肤及破损皮肤无刺激;急性毒性试验中家兔体质量变化无差异,未见死亡及中毒反应发生;家兔连续给药30 d 后凝胶剂低中高剂量组对家兔的一般情况、体质量、脏器系数及病理组织、血液学指标、血液生化学指标均无明显影响,恢复期亦无延迟性毒性反应。结论:制备的复方镰形棘豆凝胶剂是一种安全性较高的外用制剂。     

异种(猪)脱细胞真皮基质在小儿Ⅱ度烧伤创面中的应用

目的探讨应用异种(猪)脱细胞真皮基质一次包扎治疗小儿Ⅱ度烧伤的临床效果。方法回顾分析本科收治的患儿90例。烧伤面积7%～38%TBSA,烧伤深度为浅Ⅱ度和深Ⅱ。所有烧伤病例随机分两组,基质组采用异种(猪)脱细胞真皮基质一次包扎治疗,对照组采用传统的包扎疗法。比较两组的创面愈合时间和创面感染率。结果基质组的创面愈合时间和感染率明显低于对照组。结论采用异种(猪)脱细胞真皮基质一次包扎治疗小儿Ⅱ度烧伤,既能有效防止创面加深,缩短创面愈合时间,又能减轻患儿痛苦,降低感染率。     

短肽支架纤维对创面表皮碱性成纤维生长因子及表皮细胞生长因子的促进作用

目的：探讨自组装纤维支架肽RADA16在皮肤烫伤中的治疗作用。方法：在SD大鼠背部以电力机械方法制造深Ⅱ度烧伤模型,对照治疗组以0.9%NaCl溶液代替,烧伤后按时换药,并在不同时间段（伤后7、10、14d分别取烧伤修复创面的皮肤组织进行免疫组化染色,记录创面碱性成纤维细胞生长因子（bFGF）及表皮细胞生长因子（EGF）的表达,并以图像处理系统软件记录生长因子表达的半定量检测。比较了短肽处理组及空白对照组创面生长因子表达的灰度值。结果：免疫组织化学结果显示,在烧伤修复的不同修复期,短肽处理组bFGF和EGF均明显表达在新生表皮组织中,与空白对照组比较,差异均有统计学意义（P〈0.05）。结论：自组装纤维支架肽对烧伤皮肤生长因子的表达具有促进作用。     

Safety and toxicological evaluation of undenatured type II collagen

Previous research has shown that undenatured type II collagen is effective in the treatment of arthritis. The present study evaluated the broad-spectrum safety of UC-II by a variety of toxicological assays including acute oral, acute dermal, primary dermal irritation, and primary eye irritation toxicity. In addition, genotoxicity studies such as Ames bacterial reverse mutation assay and mouse lymphoma tests, as well as a dose-dependent 90-day sub-chronic toxicity study were conducted. Safety studies indicated that acute oral LD₅₀ of UC-II was greater than 5000?mg/kg in female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD₅₀ of UC-II was determined to be greater than 2000?mg/kg. Primary skin irritation tests conducted on New Zealand Albino rabbits classified UC-II as slightly irritating. Primary eye irritation tests conducted on rabbits indicated that UC-II was moderately irritating to the eye. UC-II did not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Similarly, UC-II did not induce a mutagenic effect in the gene mutation test in mouse lymphoma cells either with or without metabolic activation. A dose-dependent 90-day sub-chronic toxicity study revealed no pathologically significant changes in selected organ weights individually or as percentages of body or brain weights. No significant changes were observed in hematology and clinical chemistry. Therefore, the results from the current study show a broad-spectrum safety profile of UC-II.     

Safety and toxicological evaluation of a novel,water-soluble undenatured type II collagen

Abstract

This study was conducted to determine the broad-spectrum safety of a novel, water-soluble undenatured type II collagen (NEXT-II) derived from chicken sternum cartilage. The presence of epitope in NEXT-II was confirmed by using a commercial kit. The acute oral LD₅₀ of NEXT-II was found to be greater than 5000?mg/kg bw in rats, while the single-dose acute dermal LD₅₀ was greater than 2000?mg/kg bw. The primary dermal irritation index (PDII) of NEXT-II was found to be 1.8 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score (MMTS) of NEXT-II was observed to be 7.3 and classified as minimally irritating to the eye. Long-term safety studies were conducted in dogs over a period of 150?d, and no significant changes were observed in body weight, heart rate, respiration rate and blood chemistry. NEXT-II does not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Furthermore, two experiments were conducted to assess the potential of NEXT-II to induce mutations with and without metabolic activation at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. No biologically relevant increase of mutants was observed. Also, no dose-dependent toxicity was observed. Furthermore, colony sizing showed no clastogenic effects induced by NEXT-II under the experimental conditions. These studies demonstrated the broad spectrum of safety of NEXT-II.     

bFGF-FG对大鼠随意皮瓣早期断蒂的影响

目的探讨碱性成纤维细胞生长因子-生物蛋白胶（bFGF—FG）对大鼠随意皮瓣早期断蒂后成活率的影响。方法制备bFGF—FG,将bFGF—FG喷涂于大鼠背部随意皮瓣下方,4d后断蒂,断蒂后10d观察皮瓣成活率、微血管密度,并与单独使用bFGF组进行对比。结果皮瓣成活率bFGF—FG组为（75．6±8．91％,bFGF组为（68.3±9．3）％,对照组为（51．4±11．2）％。微血管血管密度bFGF—FG组为（24．15±6．42）／mm^2,bFGF组为（20．6±4．56）／mm^2,对照组为（13．95±5．18）／mm^2。经统计学分析,各组问差异存在显著性。结论bFGF—FG能够更好地提高随意皮瓣早期断蒂的成活率。     

重组人表皮生长因子外用治疗烧伤创面的多中心研究

目的 :观察重组人表皮生长因子 (rhEGF)治疗烧伤的疗效和安全性。方法 :以rhEGF治疗各类烧伤 30 2例 (男性 2 13例 ,女性 89例 ,年龄 33a±s 11a) ,其中试验组 (双盲自身对照 ) 190例 ,开放组112例 ,在常规治疗 ( 1%磺胺嘧啶银霜 )基础上 ,局部喷涂rhEGF或安慰剂。结果 :rhEGF用于浅Ⅱ度、深Ⅱ度、供皮区、残余创面 ,试验组较对照组愈合时间分别提前 2 ,3,3,6d ,不良反应轻微。结论 :rhEGF对烧伤创面具有明显的促进愈合的作用     

Safety and toxicological evaluation of a novel chromium(III) dinicocysteinate complex

Chromium(III) is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Chromium(III) dinicocysteinate (CDNC) is a unique form of bioavailable chromium(III). This study was focused on determining the broad spectrum safety of CDNC. Acute oral, acute dermal, primary dermal and eye irritation studies, Ames’ bacterial reverse mutation assay, mammalian erythrocyte micronucleus test, and a 90-day dose-dependent oral toxicity study were conducted. Acute oral and dermal LD₅₀ of CDNC was found to be greater than 2000?mg/kg in Sprague-Dawley rats. A primary skin irritation study in New Zealand Albino rabbits demonstrated CDNC as slightly irritating. An eye irritation study exhibited that CDNC is moderately irritating. Ames’ bacterial reverse mutation assay and mammalian erythrocyte micronucleus test demonstrated CDNC as non-mutagenic. A dose-dependent 90-day oral toxicity study demonstrated no significant toxicity of CDNC. Body weight, food and water consumption, selected organ weights (expressed as percentages of body or brain weights), ocular health, hematology, blood chemistry, and histopathology showed no abnormal changes. Clinical and histopathological evaluation of CDNC identified a dose level of 5.7?mg/kg/day as the no observed adverse effect level (NOAEL). Overall, these results demonstrate the broad spectrum safety of CDNC.     

贝复舒在鼻腔射频止血后的临床应用

目的探讨鼻腔射频后局部应用贝复舒对鼻腔粘膜恢复的影响。方法93例鼻中隔Little区鼻出血患者中,35例对照组射频后创面局部使用金霉素眼膏,58例治疗组射频后创面局部使用贝复舒凝胶,对比观察其疗效。结果10天后贝复舒治疗组治愈率为91．4％,对照组为65．7％,两组差异有统计学意义（P〈0．05）。结论贝复舒对鼻腔射频后粘膜的修复有促进作用。     

碱性成纤维细胞生长因子滴眼液在单纯疱疹性角膜炎中的应用

目的 探讨碱性成纤维细胞生长因子滴眼液治疗单纯疱疹性角膜炎的临床疗效.方法 选取我院就诊的42例单纯疱疹性角膜炎患者,随机均分为对照组和实验组,对照组患者用更昔洛韦眼用凝胶联合无环鸟苷滴眼液进行治疗,实验组患者用更昔洛韦眼用凝胶联合碱性成纤维细胞生长因子滴眼液进行治疗.比较两组患者治疗痊愈率和总有效率、角膜溃疡改善情况及不良反应发生率的差异.结果 实验组患者痊愈率和总有效率分别为66.7％和90.5％,均显著高于对照组的28.6％和61.9％ （P＜0.05）;实验组角膜溃疡改善情况显著优于对照组（P＜ 0.05）;两组患者均无不良反应发生（P＞0.05）.结论 用更昔洛韦眼用凝胶联合碱性成纤维细胞生长因子滴眼液治疗单纯疱疹性角膜炎疗效确切,见效快,无不良反应.     

Detecting the developmental toxicity of bFGF in the embryonic stem cell test using differential gene expression of differentiation-related genes

Basic fibroblast growth factor (bFGF) is a mitogenic cytokine that can stimulate mesoderm-and neuroectoderm-originated cell proliferation. This study was performed to investigate the effects of bFGF on cell differentiation and the expression of specific markers at different embryonic developmental stages. We firstly evaluated the embryotoxic potential of bFGF in vitro using a modified EST protocol. Sequentially, we further investigated how bFGF impact the different tissue-special genes and proteins expressions during the differentiation of murine ES cells in vitro and attempt to reveal the effects of bFGF on differentiation processes. This analysis was focused on key tissue- and stage-specific genes involved in ectodermal, mesodermal, and endodermal differentiation, including ectodermal-specific gene Nestin, Oligo2 and Syn, mesodermal-specific gene MHC and MyoD, and endodermal-specific gene GATA6, TTR and ALB, as well as undifferentiated gene Sox-2 and Oct-4. The results demonstrate that bFGF could promote expression of ectodermal-specific genes and protein, but suppress the expressions of endoderm-specific and some mesoderm-specific gene and protein. A conclusion can be drawn that bFGF exhibits weak embryotoxicity and mainly promotes ES cell differentiation towards the ectodermal lineages but suppress differentiation into endoderm lineages. These opposing effects of bFGF on the embryonic development of the three germ layers may be related to its weak embryotoxic potential. More specifically, inhibition of expression of the endodermal-specific markers transthyretin (TTR), and albumin (ALB) by bFGF may be of more value in detecting the embryotoxic potential of bFGF.     

Physicochemical,Morphological and Therapeutic Evaluation of Agarose Hydrogel Particles as a Reservoir for Basic Fibroblast Growth Factor

Micron-sized agarose hydrogel particles were prepared using an emulsification/gelation method as a controlled release reservoir for basic fibroblast growth factor (bFGF). Mean particle size of agarose hydrogel particles decreased with an increase in stirring speed and also with an increasing temperature of the oil phase, as measured before cooling. Morphologies of agarose particles before and after dispersing into water were investigated by scanning electron microscopy (SEM) and cryogenic SEM, respectively. Freeze-dried agarose particles were spherical with rough surface. Porous polymer matrix structure was observed in the hydrogel particles by cryo-SEM. More than 99% of bFGF was encapsulated and the release from the agarose hydrogel particles was less than 3% during the incubation in phosphate buffered saline. bFGF molecules were not only adsorbed on the particle surface but also permeated and retained within the matrix. The therapeutic efficacy of bFGF retained in agarose hydrogel particles was significantly higher than that dissolved in saline. Agarose hydrogel particle seems to be a potential candidate for a bFGF reservoir.     

Safety and healing efficacy of Sea buckthorn (Hippophae rhamnoides L.) seed oil on burn wounds in rats

The present investigation was undertaken to determine the safety and efficacy of supercritical CO₂-extracted Hippophae rhamnoides L. (Sea buckthorn) (SBT) seed oil on burn wound model. SBT seed oil was co-administered by two routes at a dose of 2.5 ml/kg body weight (p.o.) and 200 μl (topical) for 7 days on experimental burn wounds in rats. The SBT seed oil augmented the wound healing process as indicated by significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control and reference control treated with silver sulfadiazine (SS) ointment. Histopathological findings further confirmed the healing potential of SBT seed oil. SBT seed oil treatment up-regulated the expression of matrix metalloproteinases (MMP-2 and 9), collagen type-III and VEGF in granulation tissue. It was observed that SBT seed oil also possesses antioxidant properties as evidenced by significant increase in reduced glutathione (GSH) level and reduced production of reactive oxygen species (ROS) in wound granulation tissue. In acute and sub-acute oral toxicity studies, no adverse effects were observed in any of the groups administered with SBT seed oil. These results suggest that the supercritical CO₂-extracted Sea buckthorn seed oil possesses significant wound healing activity and have no associated toxicity or side effects.