论文部分内容阅读
Abstract [Objectives] An acute toxicity test of Miantan Fuzheng Powder was conducted on rabbits， which were given Miantan Fuzheng Powder at its maximum administration dosage and observed for 14 d， so as to provide reference for medicine development and clinical test.
[Methods] New zealand rabbits were divided into four groups randomly， each of which included 4 rabbits， half male and half female. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were applied with Miantan Fuzheng Powder once at a dose of 5 g/kg body weight， and the blank control groupintact skin and blank controldamaged skin groups were given the auxiliary material （vaseline） once. The rabbits were observed continuously for 14 d after the administration， and variation in body weight was recorded during the observation and then statistically analyzed with SPSS. After the 14 d of observation， the animals were killed through pentobarbital anesthesia and anatomized to observe main visceral organs including heart， liver， spleen lung and kidney. If toxic effect or organ abnormality exists， pathological sections would be prepared and observed.
[Results] Rabbits in the blank control and Miantan Fuzheng Powder groups all showed normal appearance， behavior， breath state， position and posture， response to stimulation and growth of body weight， and no irritative erythema and edema on the skin， and the damaged skin recovered naturally within 14 d. No obvious abnormality was observed on visceral organs in autopsy. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups had no significant differences in body weight from the blank control groupintact skin and blank controldamaged skin groups before administration， and on the 7th and 14th day after administration.
[Conclusions] In this acute toxicity test， the Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were given the drug at the maximum administration dosage of 5 g/kg body weight， which was about 119 times of the clinical dose for human， and no obvious toxic effect was observed.
Key words Miantan Fuzheng powder; Acute toxicity; Test
Test materials
Drug
Miantan Fuzheng Powder was provided by the Second Affiliated Hospital of Guiyang College of Traditional Chinese Medicine with a lot number： 20180528. It has the effects of clearing away heat， subsiding swelling， and promoting blood circulation to remove meridian， and is mainly used for treating peripheral facial paralysis at acute stage and local swelling and pain. Miantan Fuzheng Powder is applied externally according to the state of illness by mixing with vaseline and grease （at a ratio of power to auxiliary material of 1∶1） and adhering to local acupoints （five acupoints in total， Dicang， Jiache， Yangbai， Yifeng and Qianzheng） according to one piece （0.5 g） on each acupoint， once daily. The drug is applied for 6-8 h one time， one month as a course. That is to say 2.5 g is applied on the five acupoints one time in total， and according to the body weight of an adult of 60 kg， the daily dose is 0.042 g/kg body weight for an adult in clinic. The temporarily prepared drug is smeared onto skin with a cotton swab.
Animals
New zealand rabbits， half male and half female， with a body weight of （2.3±0.2） kg， were provided by Changsha Tianqin Biotechnology Co.， Ltd.， Certification： SCXK（xiang）20140010.
Fodder
The fodder was fullprice granular rabbit rabbits provided by above unit.
Test animal place
The animal feeding room of the Pharmacology Laboratory， Guiyang College of Traditional Chinese Medicine is clean and has good ventilation condition with a temperature of 20-25 ℃ and humidity of 55%-65%. The animals were raised separately， and ate food and drank water freely.
Main instruments
ALC210.3 type electronic balance， Shanghai Liangping Instrument Co.， Ltd.
Statistical processing
Data were all represented as x±S， and difference between groups was analyzed by t test.
Test methods and results
Trial test
The rabbits were unhaired with 8% sodium sulfide， giving a haired region with a size of 10 cm×10 cm. A certain amount of Miantan Fuzheng Powder was weighed and uniformly smeared onto the unhaired region with a cotton swab to form a thin layer on the skin rather than a thick heaped drug layer. The maximum administration dosage was thus obtained， and accordingly， the administration dosage for rabbits was calculated to be 5 g/kg： Administration dosage （g/kg）=Actual administration dosage （g）÷Body weight （kg）.
The rabbits were observed for 3 d after the application of the drug on skin. No rabbits died， indicating that its LD50 could not be determined， so the maximum administration dosage of Miantan Fuzheng Powder was determined.
Official test
16 rabbits， half male and half female， were randomly divided to blank control groupintact skin group， blank controldamaged skin group， Miantan Fuzheng Powderintact skin group and Miantan Fuzheng Powderdamaged skin group， each of which included 4 rabbits. On the day before the test， each rabbit was unhaired on the back， forming an unhaired region with a size of 10 cm×10 cm. For the blank controldamaged skin group， Miantan Fuzheng Powderdamaged skin group， the skin of rabbits was slightly scratched with a surgical knife blade， thereby preparing the damage skin which bled slightly.
On the second day of unhairing， the skin was smeared with the drug once. Specifically， the Miantan Fuzheng Powderintact skin group and Miantan Fuzheng Powderdamaged skin group were applied with Miantan Fuzheng Powder， and the blank control groupintact skin group and blank controldamaged skin group were given the auxiliary material （vaseline）， at a dose of 5 g/kg body weight， which is 119 times of the daily dose for adults （0.042 g/kg body weight）. After the drug administration， the rabbits were raised separately， to avoid lick of the drug. The rabbits ate food and drank water freely and were observed continuously for 14 d. Toxic effect on animals and variation of body weight before and after the test were recorded， and the dose， which did not cause death， was selected as the maximum administration dosage. Results： After smearing Miantan Fuzheng Powder on intact and damaged skin of rabbits at a dose of 5 g/kg body weight， the rabbits developed healthy and acted and ate normally， with strong legs， thick muscle， wellgrown hair， clear and lively eyes， and clean crissum， and no abnormal secreta was observed. During the observation， their body weights increased gradually， without remarkable differences from the blank control groupintact skin group and blank controldamaged skin group. No death and toxic and side effects were observed within 14 d. No pathological changes were observed with naked eyes. The test results are shown in Table 1 and Table 2.
Conclusions
Rabbits with intact skin or damage skin were applied with Miantan Fuzheng Powder at a dose of 5 g/kg once and observed for 14 d. During the observation， the rabbits all survived， and showed no obvious abnormality in their appearance， behavior， breath state， position and posture， response to stimulation and necropsy， and no irritative injury was observed on skin. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups had no significant differences in body weight from the blank control groupintact skin and blank controldamaged skin groups before administration， and on the 7th and 14th day after administration.
In this acute toxicity test， the Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were given the drug at the maximum administration dosage of 5 g/kg body weight， which was about 119 times of the clinical dose for human， and no obvious toxic effect was observed.
References
[1] State Drug Administration. Technical requirements for study no new traditional Chinese medicine[M]. Beijing： State Food and Drug Administration， 1999： 22.
[2] The Bureau of Drug Administration of the Ministry of Public Health. Assembly of guiding principles for new drug （western medicine） preclinical study[M]. Beijing： the Bureau of Drug Administration of the Ministry of Public Health， 1994.
[3] The Bureau of Drug Administration of the Ministry of Public Health. Guide for study on new traditional Chinese medicine[M]. Beijing： the Bureau of Drug Administration of the Ministry of Public Health， 1994： 203.
[4] XU sy. Pharmacology experiment methodology[M]. Beijing： Peoples Medical Publishing House， 2003.
[5] wang by. Development techniques and methods for new traditional Chinese medicine[M]. Shanghai： Shanghai Science and Technique Publishing House， 2001.
[Methods] New zealand rabbits were divided into four groups randomly， each of which included 4 rabbits， half male and half female. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were applied with Miantan Fuzheng Powder once at a dose of 5 g/kg body weight， and the blank control groupintact skin and blank controldamaged skin groups were given the auxiliary material （vaseline） once. The rabbits were observed continuously for 14 d after the administration， and variation in body weight was recorded during the observation and then statistically analyzed with SPSS. After the 14 d of observation， the animals were killed through pentobarbital anesthesia and anatomized to observe main visceral organs including heart， liver， spleen lung and kidney. If toxic effect or organ abnormality exists， pathological sections would be prepared and observed.
[Results] Rabbits in the blank control and Miantan Fuzheng Powder groups all showed normal appearance， behavior， breath state， position and posture， response to stimulation and growth of body weight， and no irritative erythema and edema on the skin， and the damaged skin recovered naturally within 14 d. No obvious abnormality was observed on visceral organs in autopsy. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups had no significant differences in body weight from the blank control groupintact skin and blank controldamaged skin groups before administration， and on the 7th and 14th day after administration.
[Conclusions] In this acute toxicity test， the Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were given the drug at the maximum administration dosage of 5 g/kg body weight， which was about 119 times of the clinical dose for human， and no obvious toxic effect was observed.
Key words Miantan Fuzheng powder; Acute toxicity; Test
Test materials
Drug
Miantan Fuzheng Powder was provided by the Second Affiliated Hospital of Guiyang College of Traditional Chinese Medicine with a lot number： 20180528. It has the effects of clearing away heat， subsiding swelling， and promoting blood circulation to remove meridian， and is mainly used for treating peripheral facial paralysis at acute stage and local swelling and pain. Miantan Fuzheng Powder is applied externally according to the state of illness by mixing with vaseline and grease （at a ratio of power to auxiliary material of 1∶1） and adhering to local acupoints （five acupoints in total， Dicang， Jiache， Yangbai， Yifeng and Qianzheng） according to one piece （0.5 g） on each acupoint， once daily. The drug is applied for 6-8 h one time， one month as a course. That is to say 2.5 g is applied on the five acupoints one time in total， and according to the body weight of an adult of 60 kg， the daily dose is 0.042 g/kg body weight for an adult in clinic. The temporarily prepared drug is smeared onto skin with a cotton swab.
Animals
New zealand rabbits， half male and half female， with a body weight of （2.3±0.2） kg， were provided by Changsha Tianqin Biotechnology Co.， Ltd.， Certification： SCXK（xiang）20140010.
Fodder
The fodder was fullprice granular rabbit rabbits provided by above unit.
Test animal place
The animal feeding room of the Pharmacology Laboratory， Guiyang College of Traditional Chinese Medicine is clean and has good ventilation condition with a temperature of 20-25 ℃ and humidity of 55%-65%. The animals were raised separately， and ate food and drank water freely.
Main instruments
ALC210.3 type electronic balance， Shanghai Liangping Instrument Co.， Ltd.
Statistical processing
Data were all represented as x±S， and difference between groups was analyzed by t test.
Test methods and results
Trial test
The rabbits were unhaired with 8% sodium sulfide， giving a haired region with a size of 10 cm×10 cm. A certain amount of Miantan Fuzheng Powder was weighed and uniformly smeared onto the unhaired region with a cotton swab to form a thin layer on the skin rather than a thick heaped drug layer. The maximum administration dosage was thus obtained， and accordingly， the administration dosage for rabbits was calculated to be 5 g/kg： Administration dosage （g/kg）=Actual administration dosage （g）÷Body weight （kg）.
The rabbits were observed for 3 d after the application of the drug on skin. No rabbits died， indicating that its LD50 could not be determined， so the maximum administration dosage of Miantan Fuzheng Powder was determined.
Official test
16 rabbits， half male and half female， were randomly divided to blank control groupintact skin group， blank controldamaged skin group， Miantan Fuzheng Powderintact skin group and Miantan Fuzheng Powderdamaged skin group， each of which included 4 rabbits. On the day before the test， each rabbit was unhaired on the back， forming an unhaired region with a size of 10 cm×10 cm. For the blank controldamaged skin group， Miantan Fuzheng Powderdamaged skin group， the skin of rabbits was slightly scratched with a surgical knife blade， thereby preparing the damage skin which bled slightly.
On the second day of unhairing， the skin was smeared with the drug once. Specifically， the Miantan Fuzheng Powderintact skin group and Miantan Fuzheng Powderdamaged skin group were applied with Miantan Fuzheng Powder， and the blank control groupintact skin group and blank controldamaged skin group were given the auxiliary material （vaseline）， at a dose of 5 g/kg body weight， which is 119 times of the daily dose for adults （0.042 g/kg body weight）. After the drug administration， the rabbits were raised separately， to avoid lick of the drug. The rabbits ate food and drank water freely and were observed continuously for 14 d. Toxic effect on animals and variation of body weight before and after the test were recorded， and the dose， which did not cause death， was selected as the maximum administration dosage. Results： After smearing Miantan Fuzheng Powder on intact and damaged skin of rabbits at a dose of 5 g/kg body weight， the rabbits developed healthy and acted and ate normally， with strong legs， thick muscle， wellgrown hair， clear and lively eyes， and clean crissum， and no abnormal secreta was observed. During the observation， their body weights increased gradually， without remarkable differences from the blank control groupintact skin group and blank controldamaged skin group. No death and toxic and side effects were observed within 14 d. No pathological changes were observed with naked eyes. The test results are shown in Table 1 and Table 2.
Conclusions
Rabbits with intact skin or damage skin were applied with Miantan Fuzheng Powder at a dose of 5 g/kg once and observed for 14 d. During the observation， the rabbits all survived， and showed no obvious abnormality in their appearance， behavior， breath state， position and posture， response to stimulation and necropsy， and no irritative injury was observed on skin. The Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups had no significant differences in body weight from the blank control groupintact skin and blank controldamaged skin groups before administration， and on the 7th and 14th day after administration.
In this acute toxicity test， the Miantan Fuzheng Powderintact skin and Miantan Fuzheng Powderdamaged skin groups were given the drug at the maximum administration dosage of 5 g/kg body weight， which was about 119 times of the clinical dose for human， and no obvious toxic effect was observed.
References
[1] State Drug Administration. Technical requirements for study no new traditional Chinese medicine[M]. Beijing： State Food and Drug Administration， 1999： 22.
[2] The Bureau of Drug Administration of the Ministry of Public Health. Assembly of guiding principles for new drug （western medicine） preclinical study[M]. Beijing： the Bureau of Drug Administration of the Ministry of Public Health， 1994.
[3] The Bureau of Drug Administration of the Ministry of Public Health. Guide for study on new traditional Chinese medicine[M]. Beijing： the Bureau of Drug Administration of the Ministry of Public Health， 1994： 203.
[4] XU sy. Pharmacology experiment methodology[M]. Beijing： Peoples Medical Publishing House， 2003.
[5] wang by. Development techniques and methods for new traditional Chinese medicine[M]. Shanghai： Shanghai Science and Technique Publishing House， 2001.