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)     

Immunological properties of BMY-28100 and cefepime

Immunogenicity, eliciting antigenicity and cross-reactivity of new cephem antibiotics, BMY-28100 and cefepime, were studied by means of passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and active systemic anaphylaxis in guinea pigs, and of PCA in mice and the results were compared with those obtained with reference antibiotics. In addition, the direct Coombs' reaction of the human blood was examined in vitro for the test antibiotics as compared with reference antibiotics. The results obtained are summarized as follows: 1. Immunogenicity Immunogenicity of unconjugated antibiotics was examined using the corresponding conjugates with bovine gamma-globulin (BGG) as eliciting antigen. When used as emulsions with Freund's complete adjuvant, cephalothin (CET) and benzylpenicillin (PCG) produced IgG1 and IgM antibodies in guinea pigs. However, cefepime as well as cephalexin (CEX) did not produce these antibodies, and BMY-28100 showed slightly active sensitization only for anaphylactic shock. In BALB/c and C3H/He mice, BMY-28100 and cefepime failed to produce antibodies under the experimental condition while IgE antibody formation to CET was observed. 2. Eliciting antigenicity Unconjugated CET and PCG provoked anaphylactic signs in guinea pigs sensitized with their conjugates with rabbit serum albumin (RSA). Cefepime, however, provoked no anaphylactic shock and BMY-28100 as well as CEX showed slight signs. In the other systems examined, no reactions were observed when elicited with BMY-28100, cefepime or the reference antibiotics. 3. Immunological cross-reactivity BMY-28100 did not cross-react with the reference antibiotics. While the antiserum to the RSA conjugate of CET provoked weak cross-reaction on PHA with the BGG conjugate of cefepime, the antiserum to the RSA conjugate of cefepime failed to react with the BGG conjugate of CET. Other cross-reactivities of cefepime were not observed against the reference antibiotics. 4. In vitro direct Coombs' reaction BMY-28100 did not induce the Coombs' reaction of the human blood in vitro at the testable concentration of 10 mg/ml. Cefepime or cefazolin (CEZ) caused no reaction even at a high concentration of 80 mg/ml, while CET and PCG caused a positive reaction at 10-40 mg/ml and 60 mg/ml, respectively. As shown above, immunogenicity and eliciting antigenicity of BMY-28100 and cefepime were somewhat weaker than CET and PCG but similar to CEX, and cross-reactivities of the test antibiotics with these reference antibiotics were not observed in general. The ability of BMY-28100 to give a positive reaction in the Coombs' test was weaker than that of CET, and that of cefepime was weaker than CET and PCG and equivalent to CEZ.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

莲必治注射液的过敏性研究

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。     

Allergic hypersensitivity to the insecticide malathion in BALB/c mice

The widely used insecticide malathion (diethylmercaptosuccinate, S ester with O,O-dimethylphosphorodithioate) has been reported to cause allergic responses in some exposed people and in guinea pigs. In this study, IgE antibody-mediated and cell-mediated hypersensitivity to malathion was evaluated in female BALB/c mice. To elicit malathion-specific antibodies of the IgE class, a conjugate of the anhydride of the diacid metabolite of malathion (MMA) with keyhole limpet hemocyanin was administered ip with aluminum hydroxide as adjuvant. Sera collected following three sequential sensitizations were tested for specific IgE with the passive cutaneous anaphylaxis (PCA) test in Sprague-Dawley rats. MMA coupled to bovine serum albumin was used as the challenge antigen. Specific IgE was produced following the second and third sensitization in the mice receiving 10 and 100 micrograms of conjugate and following the third sensitization in the mice receiving 1 microgram of conjugate. A paper radioallergosorbent test (PRAST) was as sensitive as and showed a good correlation with the PCA assay for samples analyzed by both procedures. Malathion applied epicutaneously on 2 days or over 4 weeks failed to elicit delayed-type hypersensitivity as determined by change in ear thickness, 5-[125I]iodo-2'-deoxyuridine incorporation in the ear, and histology of the ear following ear challenge, with or without pretreatment of the mice with cyclophosphamide. MMA-specific IgE antibodies were not detected by the PCA test in the serum of mice treated epicutaneously for 4 weeks.     

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.     

Drug-specific immune responses induced by immunization with drugs in guinea pigs and mice.

In order to develop a system for evaluating the allergenicity of drugs in clinical use, we tested drugs for the ability to induce drug-specific immune responses in guinea pigs and mice. Test drugs were benzylpenicillin, procainamide, hydralazine, isoniazid, alpha-methyldopa, D-penicillamine, captopril, sulfamethoxazole and 2,4-dinitrochlorobenzene (DNCB), which are known to induce allergic responses in man including hypersensitivity reactions and drug-induced auto-immune responses. Guinea pigs were immunized with an emulsion of complete Freund's adjuvant (CFA) and 25 mg of each drug. Mice were immunized with an emulsion of CFA and 2 mg of each drug or a mixture of aluminum hydroxide gel and 2 mg of each drug. In order to examine drug-specific immune responses, we employed detection of antibodies by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis tests, active systemic anaphylaxis (ASA) tests and delayed type hypersensitivity (DTH) tests. In guinea pigs, drug-specific antibodies were detected following immunization with benzylpenicillin, procainamide, hydralazine, isoniazid, captopril, sulfamethoxazole or DNCB. Some of these drugs were also positive in DTH tests and/or ASA tests. In mice, however, only DNCB gave positive results. Therefore, our system involving immunization of guinea pigs with CFA emulsion of a drug and detection of drug-specific immune responses is considered to be an effective test method for evaluating drug allergenicity.     

Antigenicity of suloctidil

Studies on antigenicity of suloctidil were performed on ASA, Schultz-Dale reaction, PCA and PHA in guinea pigs. Two sensitizing procedures were enforced. One was performed by means of treatment of suloctidil (p. o. and i. p.) and the other was done by means of injection of suloctidil, suloctidil-BSA-mixture and suloctidil-BSA-conjugate emulsified with FCA. Guinea pigs treated with suloctidil by oral or intraperitoneal administration showed no ASA, Schultz-Dale reaction, PCA and PHA by the challenge of suloctidil. The animals treated with suloctidil-BSA-conjugate only evoked severe anaphylactic reaction to challenge of suloctidil-OVA-conjugate. Guinea pigs treated with suloctidil and suloctidil-BSA-mixture showed no anaphylactic reaction to challenge of suloctidil, suloctidil-OVA-mixture and suloctidil-OVA-conjugate. The animals sensitized with suloctidil-BSA-conjugate showed no anaphylactic reaction to challenge of suloctidil and suloctidil-OVA-mixture. Therefore, it is concluded that suloctidil does not have any antigenicity.     

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。     

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。     

麦冬多糖平喘和抗过敏作用研究

目的 :观察麦冬多糖的平喘和抗过敏作用。方法 :通过整体实验 ,观察麦冬多糖 (POT)对氨雾引起小鼠咳嗽和对以组胺和乙酰胆碱混合液引起豚鼠支气管收缩及对小鼠耳异种被动皮肤过敏 (PCA)和以卵白蛋白诱发的致敏豚鼠支气管收缩的影响。结果 :POT 2 0 0mg/kg对氨雾引起的小鼠咳嗽无明显的影响 ;对乙酰胆碱和组胺混合液引起的豚鼠支气管收缩有极显著的抑制作用 (P <0 .0 0 1 ) ;对小鼠PCA反应的抑制率为 3 2 .79% ;可显著延长卵白蛋白所致的致敏豚鼠呼吸困难、抽搐和跌倒的潜伏期 (P <0 .0 0 1 )。结论 :麦冬多糖能拮抗乙酰胆碱和组胺混合液刺激引起的正常豚鼠和卵白蛋白引起的致敏豚鼠的支气管平滑肌收缩 ,抑制致敏豚鼠哮喘的发生并具有较显著的抗小鼠耳异种被动皮肤过敏的作用     

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 1st communication: effects on type I to type IV allergic reactions in animal models

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on type I to type IV allergic reactions were investigated by employing various animal models. WP-833 (i.v. and p.o.) dose-dependently inhibited homologous or heterologous passive cutaneous anaphylaxis (PCA) mediated by rat or mouse immunoglobulin E (IgE) in rats. Homologous PCA caused by guinea pig IgE was also inhibited by WP-833. In addition, WP-833 had inhibitory actions upon homologous PCA induced by rat or guinea pig IgG. However, WP-833 showed no inhibition of rat skin reactions caused by histamine, serotonin and bradykinin, contrasting with the inhibition of prostaglandin E1-induced skin reaction. Furthermore, both adrenalectomy and propranolol treatment exerted no influences on the inhibition of IgE-mediated homologous PCA in rats by WP-833. In contrast to above findings demonstrating that WP-833 clearly inhibited type I allergic reaction, systemic Forssman shock in guinea pigs and reversed cutaneous anaphylaxis in rats (type II), passive Arthus reaction in rats (type III), and contact dermatitis and tuberculin reaction in mice (type IV) were unaffected by WP-833 even in higher doses than in those capable of completely inhibiting type I allergic reaction.     

Antiallergic properties of an orally effective agent, [[3-(1H-tetrazol-5-yl)-phenyl] amino] oxoacetic acid n-butyl ester

A newly synthesized compound, [[3-(1H-tetrazol-5-yl)-phenyl] amino]oxoacetic acid n-butyl ester (MTB) has been demonstrated to be an orally active antiallergic agent. This compound inhibited the 48-hr passive cutaneous anaphylaxis (48-hr PCA) induced by IgE in rats. In guinea pigs, MTB also inhibited the 8-day passive cutaneous anaphylaxis (8-day PCA) and the 8-day passive systemic anaphylaxis induced by IgE. The compound partially inhibited the IgG-mediated 3-hr PCA in rats and guinea pigs, but failed to have any effect on the rabbit IgG-mediated 3-hr PCA in these animals. In the rat, MTB was not an antagonist of histamine or serotonin. The antiallergic effect of MTB was not mediated via any adrenergic mechanisms. MTB significantly inhibited histamine release from rat peritoneal cells induced by rat IgE in vitro.     

Effect of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen) on experimental allergic reactions

The effects of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen), a new anti-inflammatory agent, on experimental allergic reaction and antibody formation were examined. The action was compared with those of ketoprofen, ibuprofen, indomethacin, tranilast, chlorpheniramine, prednisolone and/or cyclophosphamide. Suprofen inhibited homologous PCA in rats, immunological histamine release from rat peritoneal mast cells and guinea pig lung tissues, Forssman cutaneous vasculitis (FCV) and the Arthus reaction in guinea pigs. The potency for inhibition of the PCA reaction was similar to that of ketoprofen and more potent than ibuprofen and trailast. As for the release of anaphylactic mediators, suprofen was less potent than tranilast in terms of histamine release, but not the release of the slow reacting substance of anaphylaxis (SRS-A). Suprofen inhibited FCA more potently than other nonsteroidal anti-inflammatory drugs (NSAID). The inhibition of the Arthus reaction by suprofen was similar to those of other NSAID and prednisolone. Suprofen hardly affected delayed hypersensitivity in guinea pigs and antibody (IgM or IgE) formation in mice or rats.     

Immunological studies on the antigenicity of the cephem antibiotic T-2588

The antigenicity or immunological characteristics of T-2588, newly-developed ester type cephem antibiotic, was studied employing rabbits, guinea pigs and mice. The results obtained were as follows: Antibody production against T-2588 was not observed in rabbit immunized with the emulsion of T-2588 and Freund's complete adjuvant (FCA). Hapten-specific antibody production against T-2525 was demonstrated by indirect hemagglutination test and 4 hrs. PCA of guinea pigs, employing rabbit antiserum hyperimmunized with the emulsion of T-2525 coupled to rabbit serum albumin and FCA. Hapten-specific antibody production against T-2525 was demonstrated by 48 hrs. PCA of rats, employing mice immunized with the mixture of T-2525 coupled to keyhole limpet hemocyanin and aluminium hydroxide gel. Cross antigenicity of T-2525 was observed to be relatively strong against cefotaxime and ceftizoxime, and very weak against cephalothin (CET), cefazolin, cefoperazone (CPZ), cefmenoxime, cefotiam and benzylpenicillin (PCG). Anaphylactic syndrome was not observed in guinea pigs actively sensitized with the emulsion of T-2588 or T-2525 and FCA. The ability of T-2588 and T-2525 to give a positive reaction in Coombs' test was rather weaker than that of CET, CPZ and PCG.     

Effect of neurotropin (NSP) on allergic reactions (author's transl)

A study was carried out to examine the effect on neurotropin (NSP) on the 4 types of allergic reactions classified by Coombs and Gell. 1) Type 1: NSP inhibited 48-hr homologous passive cutaneous anaphylaxis (PCA) as well as antigen-induced degranulation of rat mesenterium mast cells. The drug also inhibited both experimental asthma and histamine release from lung tissue in guinea pigs, as mediated by IgE antibody. 2) Type 2: NSP slightly suppressed the increase in urinary protein levels caused by nephrotoxic nephritis in rats and showed a tendency to inhibit Forssman shock in guinea pigs. NSP had an anticomplement activity in vitro but did not inhibit the reversed cutaneous anaphylaxis in rats. 3) Type 3: NSP suppressed an increase in the urinary protein level of rats with glomerulonephritis, as induced by immune complex. 4) Type 4: NSP slightly inhibited the increase in the urinary protein level in glomerulonephritic rats pretreated with IgG. However, the drug did not affect picryl chloride-induced contact dermatitis in mice. We conclude that NSP inhibits allergic reactions used in the present study except for reversed cutaneous anaphylaxis and contact dermatitis, and the most potent activity is seen in the case of Type 1 reaction.     

卡介菌多糖核酸的抗炎和抗过敏作用

目的　研究卡介菌多糖核酸 (BCG PSN)的抗炎、抗过敏作用。方法　观察对磷酸组胺所致豚鼠皮肤瘙痒的影响 ;采用二甲苯所致小鼠耳廓肿胀及角叉菜胶所致大鼠足跖肿胀实验观察抗炎作用 ;以 2 ,4 二硝基氟苯所致小鼠皮肤迟发型变态反应、大鼠同种被动皮肤过敏反应及小鼠异种被动皮肤过敏反应 ,探讨抗过敏作用。结果　豚鼠隔日肌内注射BCG PSN(0 1,0 2 ,0 4mg·kg-1) 3wk ,对磷酸组胺所致皮肤瘙痒无明显影响。小鼠隔日肌内注射BCG PSN(0 15 ,0 30 ,0 6 0mg·kg-1) 3wk ,可剂量依赖性地抑制二甲苯所致耳廓肿胀和耳异种被动皮肤过敏反应 ,高剂量时也可显著抑制 2 ,4 二硝基氟苯诱导的迟发型变态反应。大鼠隔日肌内注射BCG PSN(0 1,0 2 ,0 4mg·kg-1) 3wk ,可剂量依赖性地抑制角叉菜胶所致足跖肿胀和同种被动皮肤过敏反应。收稿日期 :2 0 0 3 -12 -2 4,修回日期 :2 0 0 4-0 2 -12作者简介 :刘桂珍 ( 1965 -) ,女 ,主管实验师 ,研究方向 :心血管药理学。Tel:0 73 1 2 3 5 5 0 77;胡长平 ( 1969-) ,男 ,博士 ,副教授 ,通迅作者 ,研究方向 :心血管药理学 ,Tel:0 73 1 2 3 5 5 0 77,E mail:huchangping2 0 0 1@yahoo .com .cn结论　BCG PSN对急性炎症、速发型变态反应和迟发型变态反应具有抑制作用。     

Effect of KC-404 on allergic reactions types I-IV

The effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a] pyridine (KC-404), a new anti-allergic agent, on type I to IV allergic reactions were investigated. KC-404 administered orally inhibited heterologous and homologous passive cutaneous anaphylaxis (PCA) reactions in guinea pigs and homologous PCA in rats; the minimum effective doses were 50, 12.5 and 3 mg/kg, respectively. However, the inhibition of PCAs by KC-404 was incomplete so that only 50 to 60% inhibitions were obtainable even at the highest doses used. KC-404 had no effect on increased vascular permeability by chemical mediators other than SRS-A and hardly affected antigen-induced degranulation of the sensitized mesenteric mast cells in vitro. These results suggest that KC-404 exerts its effect conceivably through inhibition of the SRS-A-mediated component of PCA. KC-404 had no effect on type II allergic reaction as estimated by its failure to inhibit reversed cutaneous anaphylaxis in rats and the Forssman systemic reaction in guinea pigs. Also, no influence on complement activity was observed in vitro and in vivo. KC-404 (100 approximately 200 mg/kg, p.o.) produced a marked inhibition of passive and active Arthus reactions in guinea pigs and rabbits, respectively. The tuberculin reaction in guinea pigs was not affected by KC-404. These results suggest that KC-404 inhibits PCAs mediated by IgE as well as IgG antibodies probably through a unique mechanism of action. KC-404 was shown to be effective also on type III allergic reaction.     

注射用氨磷汀安全性研究

目的研究注射用氨磷汀的安全性,为临床应用提供依据。方法进行豚鼠全身主动过敏试验(ASA),首先隔日每只豚鼠每次腹腔注射供试品,共3次,再于首次注射后第14日和第21日由耳缘静脉注射供试品,观察动物过敏反应;进行大鼠被动皮肤过敏试验(PCA),大鼠皮内注射抗体血清,静脉注射伊文思蓝,观察蓝色反应斑;进行体外溶血试验,观察供试品在3h内有无溶血和凝聚现象;进行血管刺激试验,家兔连续5 d耳缘静脉注射供试品,观察其对注射局部血管的刺激。结果注射用氨磷汀豚鼠全身主动过敏性试验及大鼠被动皮肤过敏性试验均未见过敏反应;体外溶血试验在3 h内未见溶血和凝聚现象;血管刺激性试验病理组织学检查未见血管刺激性反应。结论注射用氨磷汀安全、可靠。