CAJ | 학술논문

目的：通过?中国药典?2010年版一部附ⅫG 中药注射液安全性检查法应用指导原则中“过敏反应检查法”(以下简称为“药典法”)和?中药、天然药物免疫毒性(过敏性、光过敏反应)研究的技术指导原则?2005版中载明的方法(以下简称为“指导原则法”)分别评价并比较灯盏花素对豚鼠全身过敏反应,为药物临床前安全评价提供参考。方法将豚鼠分为阴性对照组、阳性对照组、注射用灯盏花素5和50 mg??kg-1组,分别按照“药典法”和“指导原则法”观察豚鼠对注射用灯盏花素全身主动过敏反应。致敏阶段,豚鼠 ip 给予注射用灯盏花素溶液每只0.5 mL,剂量分别为5和50 mg??kg-1,隔日1次,共3次。“药典法”在首次致敏后第14和21天 ip 给予注射用灯盏花素每只1 mL 激发；“指导原则法”在末次注射后第12天激发1次,观察豚鼠的过敏症状和过敏时间。结果“药典法”：第1次激发(首次致敏后第14天)注射用灯盏花素5 mg??kg-1组在不同时间点出现喷嚏1声和(或)搔鼻1次的现象,注射用灯盏花素50 mg??kg-1组不同时间点出现喷嚏1声或2声和(或)搔鼻1次等现象,判定过敏反应阴性。第2次激发(首次致敏后第21天)灯盏花素5 mg??kg-1组给药后分别在不同时间点出现发抖、喷嚏1声或2声和(或)搔鼻1次的现象,判定过敏反应阴性；注射用灯盏花素剂量50 mg??kg-1组4只豚鼠(4/4)给药后在不同时间点分别出现喷嚏1声和3声、咳嗽1声和2声、搔鼻1次以及排尿等现象；1只豚鼠(1/4)出现连续喷嚏3声和发抖,判定过敏反应阳性。“指导原则法”：末次注射后第12天激发,注射用灯盏花素5 mg??kg-1组激发后10 min 内均出现了不同程度的过敏反应症状,其中3只豚鼠出现搔鼻症状,为弱阳性；3只豚鼠出现喷嚏和(或)排尿症状,为阳性。注射用灯盏花素50 mg??kg-1组过敏症状包括搔鼻、喷嚏、咳嗽和(或)排尿症状,为阳性。结论在进行临床前安全性评价豚鼠全身过敏试验过程中,从动物数量、评定标准、观察时间和剂量设置等多方面要采取2种方法的优势,利用“药典法”对供试品进行初筛,一旦有疑似反应,最好采用“指导原则法”进行更加细致的观察。目的：通過?中國藥典?2010年版一部附ⅫG 中藥註射液安全性檢查法應用指導原則中“過敏反應檢查法”(以下簡稱為“藥典法”)和?中藥、天然藥物免疫毒性(過敏性、光過敏反應)研究的技術指導原則?2005版中載明的方法(以下簡稱為“指導原則法”)分彆評價併比較燈盞花素對豚鼠全身過敏反應,為藥物臨床前安全評價提供參攷。方法將豚鼠分為陰性對照組、暘性對照組、註射用燈盞花素5和50 mg??kg-1組,分彆按照“藥典法”和“指導原則法”觀察豚鼠對註射用燈盞花素全身主動過敏反應。緻敏階段,豚鼠 ip 給予註射用燈盞花素溶液每隻0.5 mL,劑量分彆為5和50 mg??kg-1,隔日1次,共3次。“藥典法”在首次緻敏後第14和21天 ip 給予註射用燈盞花素每隻1 mL 激髮；“指導原則法”在末次註射後第12天激髮1次,觀察豚鼠的過敏癥狀和過敏時間。結果“藥典法”：第1次激髮(首次緻敏後第14天)註射用燈盞花素5 mg??kg-1組在不同時間點齣現噴嚏1聲和(或)搔鼻1次的現象,註射用燈盞花素50 mg??kg-1組不同時間點齣現噴嚏1聲或2聲和(或)搔鼻1次等現象,判定過敏反應陰性。第2次激髮(首次緻敏後第21天)燈盞花素5 mg??kg-1組給藥後分彆在不同時間點齣現髮抖、噴嚏1聲或2聲和(或)搔鼻1次的現象,判定過敏反應陰性；註射用燈盞花素劑量50 mg??kg-1組4隻豚鼠(4/4)給藥後在不同時間點分彆齣現噴嚏1聲和3聲、咳嗽1聲和2聲、搔鼻1次以及排尿等現象；1隻豚鼠(1/4)齣現連續噴嚏3聲和髮抖,判定過敏反應暘性。“指導原則法”：末次註射後第12天激髮,註射用燈盞花素5 mg??kg-1組激髮後10 min 內均齣現瞭不同程度的過敏反應癥狀,其中3隻豚鼠齣現搔鼻癥狀,為弱暘性；3隻豚鼠齣現噴嚏和(或)排尿癥狀,為暘性。註射用燈盞花素50 mg??kg-1組過敏癥狀包括搔鼻、噴嚏、咳嗽和(或)排尿癥狀,為暘性。結論在進行臨床前安全性評價豚鼠全身過敏試驗過程中,從動物數量、評定標準、觀察時間和劑量設置等多方麵要採取2種方法的優勢,利用“藥典法”對供試品進行初篩,一旦有疑似反應,最好採用“指導原則法”進行更加細緻的觀察。
목적：통과?중국약전?2010년판일부부ⅫG 중약주사액안전성검사법응용지도원칙중“과민반응검사법”(이하간칭위“약전법”)화?중약、천연약물면역독성(과민성、광과민반응)연구적기술지도원칙?2005판중재명적방법(이하간칭위“지도원칙법”)분별평개병비교등잔화소대돈서전신과민반응,위약물림상전안전평개제공삼고。방법장돈서분위음성대조조、양성대조조、주사용등잔화소5화50 mg??kg-1조,분별안조“약전법”화“지도원칙법”관찰돈서대주사용등잔화소전신주동과민반응。치민계단,돈서 ip 급여주사용등잔화소용액매지0.5 mL,제량분별위5화50 mg??kg-1,격일1차,공3차。“약전법”재수차치민후제14화21천 ip 급여주사용등잔화소매지1 mL 격발；“지도원칙법”재말차주사후제12천격발1차,관찰돈서적과민증상화과민시간。결과“약전법”：제1차격발(수차치민후제14천)주사용등잔화소5 mg??kg-1조재불동시간점출현분체1성화(혹)소비1차적현상,주사용등잔화소50 mg??kg-1조불동시간점출현분체1성혹2성화(혹)소비1차등현상,판정과민반응음성。제2차격발(수차치민후제21천)등잔화소5 mg??kg-1조급약후분별재불동시간점출현발두、분체1성혹2성화(혹)소비1차적현상,판정과민반응음성；주사용등잔화소제량50 mg??kg-1조4지돈서(4/4)급약후재불동시간점분별출현분체1성화3성、해수1성화2성、소비1차이급배뇨등현상；1지돈서(1/4)출현련속분체3성화발두,판정과민반응양성。“지도원칙법”：말차주사후제12천격발,주사용등잔화소5 mg??kg-1조격발후10 min 내균출현료불동정도적과민반응증상,기중3지돈서출현소비증상,위약양성；3지돈서출현분체화(혹)배뇨증상,위양성。주사용등잔화소50 mg??kg-1조과민증상포괄소비、분체、해수화(혹)배뇨증상,위양성。결론재진행림상전안전성평개돈서전신과민시험과정중,종동물수량、평정표준、관찰시간화제량설치등다방면요채취2충방법적우세,이용“약전법”대공시품진행초사,일단유의사반응,최호채용“지도원칙법”진행경가세치적관찰。
OBJECTIVE To compare the difference of methods for active systemic anaphylactic reaction induced by breviscapine injection between ″Pharmacopoeia″ 2010 edition, an Attached ⅫG in Traditional Chinese Medicine lnjection Safety Test Application Guidelines ″ Anaphylactic Reaction Test″(thereafter referred to as the method of ″Pharmacopoeia″) and the Traditional Chinese Medicine, Natural Medicine lmmune Toxicity (Anaphylaxis, Anaphylactic Reaction of Light) Technology Guiding Principles in the 2005 Version (thereafter referred to as the method of ″Guiding Principle″) and provide reference for non-clinical safety evaluation of drugs. METHODS According to the methods of ″Pharmacopoeia″and ″Guiding Principle″, respectively, the effect of breviscapine injection on active systemic anaphylactic reaction of guinea pigs was investigated. The guinea pigs were divided into four groups, negative control group, positive control group, breviscapine injection 5 and 50 mg.kg-1 groups. ln the sensitization phase, the guinea pigs were ip administrered with breviscapine injection 0.5 mL each every other day for 3 times. The dose was 5 and 50 mg.kg-1 , respectively. For the method of ″Pharmacopoeia″, on the 14th and 21st days after the first sensitization, the guinea pigs were iv administrered with breviscapine injec-tion 1 mL. For the method of ″Guiding Principle″, the guinea pigs were provocated on the 12th day after the first sensitization. Each group was studied by observing the symptom of anaphylactic reaction and immune time. RESULTS For the method of ″Pharmacopoeia″, on the 14th day after the first sensitization, there was 1 guinea pig with sneezing and (or) the nose-scratching at different time in the 5 mg.kg-1 group. ln the 50 mg.kg-1 group, there was one or two cases of sneezing and (or) 1 case of nose-scratc-hing. The 5 and 50 mg.kg-1 dose groups conformed to the regulations. On the 21st day after the first sensitization, trembling occurred in the 5 mg.kg-1 group, with 1 or 2 guinea pigs sneezing and ( or) scratching the nose. There were 4 guinea pigs (4/ 4) with sneezing 1 and 3 times, cough once or twice, 1 scratching nose and urination at different time, and 1 guinea pigs (1/ 4) appeared 3 times consecutive sneezing and shivering in 50 mg.kg-1 group. The 5 mg.kg-1 group conformed to the regulations, while the 50 mg.kg-1 group did not. For the method of ″Guiding Principle″, the 5 mg.kg-1 group was weak positive or positive, with different degrees of symptoms of an anaphylactic reaction, including 3 guinea pigs scratched nasal symptoms. And the 50 mg.kg-1 group of anaphylactic symptoms including scratc-hing nose, sneezing, coughing and (or) urination, showed positive. CONCLUSION During the active systemic anaphylactic reaction of drugs non-clinical safety evaluation of drugs the advantage of either method should be brought into play. The method of ″ Pharmacopoeia″ may be used for preliminary screening of test samples. ln case pf suspected reactions, the method of ″Guiding Principle″ should be used for more detailed observations.