莲必治注射液的过敏性研究

摘 要 目的: 研究两种不同纯度的莲必治注射液在被动皮肤过敏试脸(passive cutaneous anaphylaxis,PCA)和全身主动过敏试验(active systemic anaphylaxis,ASA)中是否有过敏反应。方法: 按照《中药、天然药物免疫毒性(过敏性、光变态反应)研究的技术指导原则》的试验方法对两种不同纯度的莲必治注射液进行被动皮肤过敏试验和全身主动过敏试验研究。结果:被动皮肤过敏试验中两种莲必治液均有过敏反应。在全身主动过敏试验中,莲必治A 高剂量组有2只动物出现弱阳性,而莲必治B 高剂量组1只出现弱阳性,5只出现阳性反应,2只出现过敏反应的极强阳性反应,其他未见过敏反应。结论:莲必治注射液所引发的过敏反应可能与其所含的杂质有关。     

几种中药注射液的过敏性研究

目的:研究参麦注射液、穿琥宁注射液和黄芪注射液在皮肤被动过敏试验(PCA)和全身主动过敏试验(ASA)中是否有过敏反应。方法:按照《中药、天然药物免疫毒性(过敏性、光变态反应)研究的技术指导原则》的试验方法对以上3种中药注射液进行皮肤被动过敏试验和全身主动过敏试验研究。结果:皮肤被动过敏试验麦参注射液和穿琥宁注射液高剂量组和低剂量组均有过敏反应;黄芪注射液高剂量组出现过敏反应,低剂量组未见过敏反应。主动过敏试验只有穿琥宁注射液高剂量组2只动物过敏反应弱阳性,其它未见过敏反应。结论:对于参麦注射液、穿琥宁注射液和黄芪注射液3种中药注射液而言,与临床实际使用情况相比,大鼠皮肤被动过敏性试验具有比全身主动过敏试验更好的相关性。     

银黄注射液刺激性、过敏性和溶血性试验研究

目的观察银黄注射液是否具有血管刺激性、过敏性和溶血性。评价其注射用药的安全性。方法通过兔耳缘静脉刺激性试验、豚鼠全身主动过敏性试验(ASA)和大鼠被动皮肤过敏试验(PCA)、体外溶血性试验观察银黄注射液的安全性。结果银黄注射液对家兔耳静脉和肌肉有轻微的刺激性;豚鼠全身主动过敏性试验无动物出现过敏症状;在大鼠被动皮肤过敏试验中仅高剂量组25%动物出现过敏反应症状;对家兔血细胞无溶血和凝集反应。结论在本次实验条件下除银黄注射液低高剂量组有轻微过敏反应症状外,其注射使用是安全的。     

不同剂型紫杉醇注射液过敏反应的比较研究

目的比较不同剂型紫杉醇注射液引起的过敏反应及类过敏反应,为研究紫杉醇新剂型提供依据。方法采用豚鼠进行主动全身过敏试验,SD大鼠进行被动皮肤过敏试验,ICR小鼠进行类过敏试验。结果豚鼠主动过敏试验:市售紫杉醇注射液出现弱阳性,乳剂稀释用紫杉醇注射液无症状,注射用紫杉醇(白蛋白结合型)弱阳性。SD大鼠被动过敏试验:市售紫杉醇注射液和乳剂稀释用紫杉醇注射液均无症状,注射用紫杉醇(白蛋白结合型)呈阳性。ICR小鼠类过敏试验:乳剂稀释用紫杉醇注射液和注射用紫杉醇(白蛋白结合型)均未出现阳性结果,市售紫杉醇注射液与50%Cr EL组出现强阳性结果,市售紫杉醇注射液组伊文思蓝渗出量明显高于另外2组。结论根据行为症状、皮肤蓝染率以及伊文思蓝渗出率指标判断,乳剂稀释用紫杉醇注射不引起过敏反应及类过敏反应,紫杉醇注射液(白蛋白结合型)引起的过敏反应可能与紫杉醇对免疫功能的影响有关,但不引起类过敏反应;传统市售紫杉醇注射液所产生的过敏症状属于类过敏反应,可能由其制剂中所含聚氧乙烯蓖麻油引起。     

几种临床引发Ⅰ型过敏反应的中药注射剂致敏性再评价

目的 通过主动全身过敏试验（ASA）及被动皮肤过敏试验（PCA）对几种临床易于发生Ⅰ型过敏反应的中药注射剂的致敏性进行再评价.方法 取生理盐水、卵蛋白、清开灵注射液、生脉注射液、丹参注射液、喜炎平注射液对豚鼠进行主动全身过敏试验和大鼠被动皮肤过敏试验：（1）Elisa法检测主动全身过敏试验中采集的豚鼠血浆中IgE、组胺、类胰蛋白酶、β-氨基己糖苷酶的含量.（2）观察被动皮肤过敏试验中大鼠背部出现的蓝斑情况.结果 主动全身过敏试验中卵蛋白组、生脉注射液组、丹参注射液组豚鼠血浆中IgE、组胺及β-氨基己糖苷酶含量均高于生理盐水组;被动皮肤过敏试验中卵蛋白组、生脉注射液组、丹参注射液组可见明显蓝斑.结论 主动全身过敏试验结合被动皮肤过敏试验表明卵蛋白、生脉注射液、丹参注射液、清开灵注射液有致敏性,可引起Ⅰ型过敏反应的发生.     

磷酸川芎嗪注射液血管刺激性、溶血性及过敏性试验研究

目的观察磷酸川芎嗪注射液是否具有血管刺激性、溶血性和过敏作用,评价其注射用药的安全性。方法通过兔耳缘静脉刺激性试验、体外溶血性试验、豚鼠全身主动过敏性试验（ASA）和大鼠被动皮肤过敏试验（PCA）,试验观察磷酸川芎嗪注射液的安全性。结果磷酸川芎嗪注射液对家兔耳静脉注射无明显刺激性;对家兔血细胞无溶血和凝集反应;豚鼠全身主动过敏性试验亦无动物出现过敏症状;在大鼠被动皮肤过敏试验中仅低剂量组有20%动物出现过敏反应症状。结论在本次实验条件下,除磷酸川芎嗪注射液低剂量组有轻微过敏反应症状外,其注射使用是安全的。     

银杏内酯注射液Ⅰ型过敏反应的研究

目的 探索银杏内酯注射液在静脉给药后产生的Ⅰ型过敏反应,为临床安全用药提供参考.方法 采用豚鼠做全身主动过敏试验;采用BALB/c小鼠制备抗血清,以SD大鼠做被动皮肤过敏试验.结果 全身主动过敏试验致敏期间和激发后给药组和阴性组豚鼠无异常症状,阳性组豚鼠出现明显过敏症状;被动皮肤过敏试验给药组和阴性组大鼠背部未出现蓝斑,阳性组蓝斑直径均值＞5 mm.结论 银杏内酯注射液在此试验条件下,全身主动过敏和被动皮肤过敏试验结果为阴性.     

毛冬青注射液的刺激、溶血与过敏反应研究

目的:研究毛冬青注射液的安全性,为临床合理用药提供依据.方法:通过豚鼠主动过敏试验(ASA)和被动皮肤过敏试验(PCA),考察过敏反应;通过体外溶血试验,观察溶血和凝聚现象;通过肌肉和血管等局部刺激试验,考察对肌肉和血管的局部刺激作用.结果:豚鼠主动过敏试验及被动皮肤过敏试验均未见过敏反应;体外溶血试验未见溶血和凝聚现象;局部刺激试验未见刺激反应.结论:本批研究的毛冬青注射液安全性较好.     

艾迪注射液安全性试验研究

目的:对艾迪注射液进行豚鼠主动全身过敏反应试验、大鼠被动皮肤过敏反应试验、溶血试验、肌肉刺激性及血管刺激性试验.为其临床应用提供安全性依据.方法:豚鼠主动全身过敏反应,在第1次给药后14 d及21 d,分别从足背静脉注射艾迪注射液观察注射后30 min动物的过敏症状;大鼠被动皮肤过敏试验,采用伊文思蓝溶液分析法;体外溶血试验,观察本品在3 h内有无溶血和聚集现象;肌肉刺激性试验,观察2只家兔注射艾迪注射液后48 h的变化;血管刺激性试验,观察连续用药5 d艾迪注射液及生理盐水,以及恢复14 d后的注射局部血管和周围组织反应情况.结果:艾迪注射液对豚鼠主动全身过敏反应及大鼠被动皮肤过敏反应均未见明显过敏反应;未见明显体外溶血作用;对家兔股四头肌、耳缘静脉未见明显刺激作用.结论:艾迪注射液的安全性试验结果提示其安全可靠.     

盐酸克林霉素注射液部分安全性试验

目的 评价盐酸克林霉素注射液注射给药的安全性.方法 采用家兔耳缘静脉血管刺激性试验、肌肉刺激性试验、体外溶血性试验、豚鼠全身主动过敏试验和大鼠被动皮肤过敏试验等方法进行研究.结果 盐酸克林霉素注射液静脉滴注对给药部位血管无明显刺激作用,肌内注射给药对注射部位有一定的刺激性;豚鼠全身主动过敏反应和大鼠被动皮肤过敏反应为阴性;对家兔红细胞无溶血和凝集作用.结论 试验所用的盐酸克林霉素注射液临床静脉滴注给药安全性较好,肌内注射给药对注射部位具有刺激性.     

不同来源白花蛇舌草注射液过敏反应比较研究

目的研究白花蛇舌草注射液的致敏性并比较不同来源白花蛇舌草注射液过敏反应的差别,遴选优质药品。方法将实验动物分为阴性对照组、阳性对照组(卵清蛋白)、白花蛇舌草注射液组,通过豚鼠主动全身过敏反应(ASA)试验和大鼠皮肤被动过敏反应(PCA)试验对白花蛇舌草注射液的致敏性进行研究。结果 A厂家和C厂家ASA试验和PCA试验均为阴性,B厂家除两批样品PCA试验为阳性外,其余样品ASA试验和PCA试验为阴性。结论不同厂家生产的白花蛇舌草注射液由于生产条件不同等原因,其过敏反应存在差别,其鞣质的含量可能与PCA有关。     

黄芪甲苷注射液动物过敏性研究

目的 采用主动全身过敏试验（ASA）和被动皮肤过敏试验（PCA）以及血清样本效价测定,综合评价黄芪甲苷注射液对动物的致敏作用,为临床拟用的安全性提供参考。方法 ASA：选用豚鼠作为实验动物,0.4、1.6 mg/kg黄芪甲苷注射液间日致敏5次,末次致敏后11 d,3倍剂量进行激发,观察30 min内动物过敏症状;PCA：选用大鼠作为实验动物,0.5、2.0 mg/kg黄芪甲苷注射液间日致敏5次,制备抗血清;将致敏血清稀释后sc给予另一批大鼠进行被动致敏,约48 h后激发,30 min后麻醉处死,观察皮肤过敏反应;间接酶联免疫吸附测定法（ELISA）检测制备的抗血清中的抗体效价。结果 ASA：黄芪甲苷注射液在0.4、1.6 mg/kg剂量下各只豚鼠均未出现任何过敏反应,即过敏反应阴性;PCA：黄芪甲苷注射液0.5、2.0 mg/kg剂量下大鼠被动过敏反应均为阴性,血清样本中不存在针对黄芪甲苷的特异性抗体。结论 黄芪甲苷注射液体内ASA和PCA试验均无过敏反应,动物血清中不存在针对黄芪甲苷药物的特异性抗体,提示临床使用出现过敏反应的可能性较小。     

注射用头孢曲松钠溶血性、局部刺激性和过敏反应一致性评价

目的 采用溶血性、血管刺激性试验、肌肉刺激性试验和全身主动过敏试验（ASA）检测受试物注射用头孢曲松钠与市售对照品（罗氏芬）局部毒性和过敏性,进行一致性评价。方法 分别采用肉眼观察法和分光光度法进行体外溶血性试验;以受试物或市售对照品临床iv最高浓度（93 mg·mL^-1）连续4 d耳缘静脉推注给药进行新西兰兔血管刺激性试验;以临床im最高浓度（238 mg·mL^-1,给药体积1 mL）连续4 d右后肢股四头肌im给药进行新西兰兔肌肉刺激性试验;采用传统豚鼠ASA进行过敏性试验,致敏剂量分别0.5、1.5 mg·kg^-1,激发剂量分别为1.0、3.0 mg·kg^-1。结果 肉眼观察法和分光光度法均显示受试物及市售对照品无体外溶血和红细胞凝聚作用;临床等效剂量的受试物及市售对照品均无血管刺激性;最大给药浓度的受试物及市售对照品在末次给药后72 h均有重度肌肉刺激性,恢复期结束时受试物组与市售对照品组动物注射部位肌肉均见纤维化等正常修复现象;受试物及市售对照品均可见弱阳性全身致敏作用,结果具有一致性。结论 受试物注射用头孢曲松钠与市售对照品局部毒性反应和过敏反应情况基本一致,可用于临床。     

Immunological properties of S-1090, cefmatilen hydrochloride hydrate

S-1090, a cefmatilen hydrochloride hydrate, is being developed as a cephalosporin antibiotic for oral use. Immunogenicity, hypersensitivity-eliciting antigenicity and immunological cross-reactivity with other antibiotics were evaluated by active systemic anaphylaxis (ASA) test, passive cutaneous anaphylaxis (PCA) test and enzyme-linked immunosorbent assay (ELISA) using guinea pigs and mice/rats. In addition, in vitro direct Coombs' test was also performed to examine the possibility of hemolytic anemia in clinical use. Immunogenicity of S-1090 was not observed in guinea pigs after repeated immunization with S-1090 by ASA or PCA tests. Even in ELISA, only weak antibody production against S-1090 was found in some guinea pigs from the intraperitoneal groups showing the antibody titers only 10(1) to 10(2). When the sera collected from C3H/He mice and C57BL/6J mice immunized with S-1090 were tested for immunogenicity, rat PCA was elicited in a C3H/He mouse serum by S-1090 and antibodies against S-1090 were detected in a C57BL/6J mouse serum by ELISA. When adjuvant was used in mice and guinea pigs, the production of antibody against S-1090 was less frequent in comparison with other antibiotics such as cefmetazole (CMZ) and cefotiam (CTM). When hypersensitivity-eliciting antigenicity of S-1090 was examined using S-1090 as an eliciting antigen in ASA and PCA tests, positive ASA and PCA were observed in guinea pigs and positive PCA in a C3H/He mouse. Hypersensitivity-eliciting antigenicity was also observed in other reference antibiotics, i.e. cephalothin (CET), CMZ and CTM. Immunological cross-reactivity among S-1090, penicillin G (PCG), CET, CMZ and CTM was tested by ASA and PCA tests. S-1090 was found to immunologically cross-react only with CET in guinea pigs. In the present study, immunological cross-reactivities were also noted between PCG and CET, PCG and CMZ, PCG and CTM, and between CET and CMZ. In in vitro direct Coombs' test using human red blood cells, S-1090.Na, PCG and CET gave positive reactions at the final concentrations of 40 mg/mL, 20 to 40 mg/mL and 2.5 to 10 mg/mL, respectively.     

Diospyros kaki calyx inhibits immediate-type hypersensitivity via the reduction of mast cell activation

Context: Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects.

Objective: We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action.

Materials and methods: For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1–100?mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1?h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01–1?mg/mL).

Results: Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10?mg/kg), AEDKC (100?mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and β-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1?mg/mL) was similar with dexamethasone (10?μM) in vitro.

Conclusions: We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.     

Antigenicity tests on propiverine hydrochloride in guinea pigs and mice

Antigenicity of propiverine hydrochloride (P-4), a newly developed drug for pollakisuria, was investigated in guinea pigs and mice. 1. Two strains of mice (BALB/c and C3H/He) showed no production of antibodies against P-4 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous passive cutaneous anaphylaxis (PCA) test using rats. On the other hand, antibodies against P-4-ovalbumin (OVA) conjugate inoculated with alum was definitely detected. 2. In the studies with guinea pigs, both the inoculation of P-4 alone and of P-4 with Freund's complete adjuvant (FCA) as an adjuvant did not produce positive reactions in any of homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA) and passive hemagglutination (PHA) tests. On the other hand, the inoculation of P-4-OVA conjugate with FCA produced positive reaction in all of PCA, ASA and PHA tests. 3. In the active cutaneous anaphylaxis (ACA) test in guinea pigs inoculated with P-4-OVA conjugate with FCA, positive reaction was produced by eliciting injection of P-4-human serum albumin (HSA). 4. In the Schultz-Dale reaction test, any animals in any groups showed no positive reaction to both eliciting antigens, P-4 and P-4-HSA. 5. These findings showed that P-4 had no antigenicity in guinea pigs and mice.     

Antigenicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]

The antigenicity of Z-103 (catena-(S)-[mu[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) was evaluated using the following assay procedures: 1. active systemic anaphylaxis (ASA) in guinea pigs. 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum from guinea pigs sensitized with Z-103, 3. delayed type skin reaction (Maximization Test) in guinea pigs, 4. passive cutaneous anaphylaxis (PCA) in rats with serum from mice sensitized with Z-103 and 5. passive hemagglutination (PHA) with serum from mice sensitized with Z-103. In each test except for Maximization Test, the sera obtained 1 or 6 h (hereinafter designated as 1-h-sera or 6-h-sera) after a single oral administration of 500 mg/kg of Z-103 to the unused rats, guinea pigs or rabbits, were used as the challenge antigen. 1. ASA in guinea pigs: No anaphylaxis reaction was observed in any of the sensitized guinea pigs by elicitation with challenge antigen. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1 in elicitation with the challenge antigen. 3. Delayed type skin reaction test: No skin reaction was observed in sensitized guinea pigs after intradermal injection or dermal application of Z-103. 4. PCA in rats: PCA titer of sera from BALB/c and C3H/He mice sensitized with Z-103 was less than 5 in elicitation with the challenge antigen. 5. PHA reaction: When erythrocytes coated with challenge antigen were added to sensitized sera, the hemagglutination titer was less than 1.(ABSTRACT TRUNCATED AT 250 WORDS)