抗中暑速效喷雾剂的研究
摘要
抗中暑速效喷雾剂是由诸葛行军散经处方筛选，由传统的散剂改革而成，具有作用迅速、剂量小、给药方便等特点。
目的：1)对诸葛行军散进行处方筛选，在不改变疗效的情况下制定更适合本剂型的处方。
2)建立麝香酮、胆酸含量测定方法。
3)筛选出干姜、霍香挥发油、牛黄、麝香的最佳提取工艺。
4)筛选成型工艺。
5)制定质量标准。
方法：1)将经不同处理的大鼠热暴露人工气候室里(温度41℃、相对湿度70％)，测定各组大鼠肛温及死亡时间，考察了抗中暑速效喷雾剂与诸葛行军散在降低大鼠体温、延长存活时间、降低死亡率上的差异。
2)麝香酮的含量测定采用了GC法，胆酸的含量测定采用了紫外分光光度法，
3)采用正交设计方法筛选干姜、霍香挥发油、麝香、牛黄的最佳提取工艺和成型工艺。
4)采用已建立好的麝香酮、胆酸的含量测定方法确定麝香酮、胆酸的含量。采用薄层色谱法对冰片、霍香、干姜进行定性鉴别。
结果：1)抗中暑速效喷雾剂能明显地降低热环境下大鼠肛温、死亡率和延长大鼠存活时间，且效果好于诸葛行军散。
2)麝香酮、胆酸的含量测定方法的线性回归方程和相关系数分别为y=-0.00114+1.099×10~(-9)，R=0.9999；y=-0.365+18.86x，(ug／ml) R=0.9999。加样回收率分别为麝香酮为98.82—101.71％ 胆酸99.41—102.03％稳定性、精密度、重现性的RSD均小于1％
3)霍香和干姜挥发油、牛黄、麝香最佳提取工艺分别为：10倍量的水水蒸汽蒸馏7小时；20倍量的氯仿超声提取两次，每次20分钟；加10倍量的乙酸乙酯超声提取两次，每次20分钟。
4)成品麝香酮、胆酸的含量分别0.0493—0.0553mg／ml、0.3974—0.5227mg／ml含量均介于相应的口服液与注射液之间。
结论：抗中暑速效喷雾剂经过处方筛选、提取工艺、成型工艺的研究、各
项指标表明该制剂具有组方合理、疗效显著、工艺可行、质量可控。为下
一步实验提供基础。
pharmaceutics of quick result resist heat stroke is adjusted from the ZhuGeXinJun powder through prescription screening. It is more effective for the prevention of heat Stroke. Objective:
1) To obtain a new prescription which is more suit for spray on the base of the prescription of ZhuGeXinJun powder.
2) To develop a assay method for Muscone and cholalic.
3) To screen the best extract technique for Volatile oil, cow-bezoar and Musk.
4) To screen a moulding technique.
5) To enact a quality criterion. Methods:
1) Heat exposure rats which have been treated with several different methods in phytotron (41?, relative humidity 70%), estimated the death time and the temperature from the anus of the rat, and then compare the difference of the temperature, survival data and mortality between the Preventive heat Stroke Spray and the ZhuGeXinJun powder.
2) Using the GC method to assay the content of Muscone, using the UV spectrophotometer to assay the content of cholalic acid.
3) Orthogonal design was used to screen the best extract method and moulding method for Volatile oil, Musk and cow-bezoar.
4) Using developed content assay methods to estimate the contents of Muscone and cholalic acid. Thin layer chromatogram scanner was used to qualitative Identificate the borneo camphor Pogostemon and dried ginger.
Results:
1) Preventive heat Stroke Spray is better for decreasing the temperature, amelioration survival data and decreasing mortality than the
ZhuGeXinJun powder in a low-heat enviroment.
2) The linear regression equation and correlation coefficient of content assay methods for Muscone is y=-0.00114+1.099x109 , R=0.9999. and the linear regression equation and correlation coefficient of content assay methods for cholalic acid is y=-0.365+18.86x (ug/ml) R=0.9999. The callback rate for Muscone is 98. 88-101. 71% .The callback rate for cholalic acid is 99.41- 102.03%. All the RSDs of stability, precision and reduplication for both Muscone and cholalic acid are less than 1%.
3) The best extract technique for Pogostemon dried ginger Volatile oil ,cow-bwzoar and Musk is stilling Pogostemon and dried ginger Volatile oil with ten times quantity ree for 7 hours; ultrasound extraction cow-bwzoar twice times with 20 times Chloroform, each tune is 20minutes; ultrasound extraction Musk twice times with 20 times acetic ether, each time is 20minutes.
4) The content of Musk is 0.0493-0.0553mg/ml. The content of cholalic acid is 0.3974-0.5227 mg/ml. Both contents are between Oral drug preparation and parenteral solution and its suits for norm of Spray.
Conclusion:
Through the screening of prescription ,extraction methods and mouding methods, we get the end product of Preventive heat Stroke Spray .All the assay results show the prescription is reasonable, the effect is significant, the technique is feasible and its quality can be controlled . All above has done a foundation for the next study.
目的：1)对诸葛行军散进行处方筛选，在不改变疗效的情况下制定更适合本剂型的处方。
2)建立麝香酮、胆酸含量测定方法。
3)筛选出干姜、霍香挥发油、牛黄、麝香的最佳提取工艺。
4)筛选成型工艺。
5)制定质量标准。
方法：1)将经不同处理的大鼠热暴露人工气候室里(温度41℃、相对湿度70％)，测定各组大鼠肛温及死亡时间，考察了抗中暑速效喷雾剂与诸葛行军散在降低大鼠体温、延长存活时间、降低死亡率上的差异。
2)麝香酮的含量测定采用了GC法，胆酸的含量测定采用了紫外分光光度法，
3)采用正交设计方法筛选干姜、霍香挥发油、麝香、牛黄的最佳提取工艺和成型工艺。
4)采用已建立好的麝香酮、胆酸的含量测定方法确定麝香酮、胆酸的含量。采用薄层色谱法对冰片、霍香、干姜进行定性鉴别。
结果：1)抗中暑速效喷雾剂能明显地降低热环境下大鼠肛温、死亡率和延长大鼠存活时间，且效果好于诸葛行军散。
2)麝香酮、胆酸的含量测定方法的线性回归方程和相关系数分别为y=-0.00114+1.099×10~(-9)，R=0.9999；y=-0.365+18.86x，(ug／ml) R=0.9999。加样回收率分别为麝香酮为98.82—101.71％ 胆酸99.41—102.03％稳定性、精密度、重现性的RSD均小于1％
3)霍香和干姜挥发油、牛黄、麝香最佳提取工艺分别为：10倍量的水水蒸汽蒸馏7小时；20倍量的氯仿超声提取两次，每次20分钟；加10倍量的乙酸乙酯超声提取两次，每次20分钟。
4)成品麝香酮、胆酸的含量分别0.0493—0.0553mg／ml、0.3974—0.5227mg／ml含量均介于相应的口服液与注射液之间。
结论：抗中暑速效喷雾剂经过处方筛选、提取工艺、成型工艺的研究、各
项指标表明该制剂具有组方合理、疗效显著、工艺可行、质量可控。为下
一步实验提供基础。
pharmaceutics of quick result resist heat stroke is adjusted from the ZhuGeXinJun powder through prescription screening. It is more effective for the prevention of heat Stroke. Objective:
1) To obtain a new prescription which is more suit for spray on the base of the prescription of ZhuGeXinJun powder.
2) To develop a assay method for Muscone and cholalic.
3) To screen the best extract technique for Volatile oil, cow-bezoar and Musk.
4) To screen a moulding technique.
5) To enact a quality criterion. Methods:
1) Heat exposure rats which have been treated with several different methods in phytotron (41?, relative humidity 70%), estimated the death time and the temperature from the anus of the rat, and then compare the difference of the temperature, survival data and mortality between the Preventive heat Stroke Spray and the ZhuGeXinJun powder.
2) Using the GC method to assay the content of Muscone, using the UV spectrophotometer to assay the content of cholalic acid.
3) Orthogonal design was used to screen the best extract method and moulding method for Volatile oil, Musk and cow-bezoar.
4) Using developed content assay methods to estimate the contents of Muscone and cholalic acid. Thin layer chromatogram scanner was used to qualitative Identificate the borneo camphor Pogostemon and dried ginger.
Results:
1) Preventive heat Stroke Spray is better for decreasing the temperature, amelioration survival data and decreasing mortality than the
ZhuGeXinJun powder in a low-heat enviroment.
2) The linear regression equation and correlation coefficient of content assay methods for Muscone is y=-0.00114+1.099x109 , R=0.9999. and the linear regression equation and correlation coefficient of content assay methods for cholalic acid is y=-0.365+18.86x (ug/ml) R=0.9999. The callback rate for Muscone is 98. 88-101. 71% .The callback rate for cholalic acid is 99.41- 102.03%. All the RSDs of stability, precision and reduplication for both Muscone and cholalic acid are less than 1%.
3) The best extract technique for Pogostemon dried ginger Volatile oil ,cow-bwzoar and Musk is stilling Pogostemon and dried ginger Volatile oil with ten times quantity ree for 7 hours; ultrasound extraction cow-bwzoar twice times with 20 times Chloroform, each tune is 20minutes; ultrasound extraction Musk twice times with 20 times acetic ether, each time is 20minutes.
4) The content of Musk is 0.0493-0.0553mg/ml. The content of cholalic acid is 0.3974-0.5227 mg/ml. Both contents are between Oral drug preparation and parenteral solution and its suits for norm of Spray.
Conclusion:
Through the screening of prescription ,extraction methods and mouding methods, we get the end product of Preventive heat Stroke Spray .All the assay results show the prescription is reasonable, the effect is significant, the technique is feasible and its quality can be controlled . All above has done a foundation for the next study.
引文
[1] MarinoAetal.MinervaAnestesia, 1992;58(6):39302
[2] DahmashNSetal.Chest, 1993; 103(4): 1210-121403
[3] YoungMSetal.ChinJPhysiol, 1993;36(4): 193-19804
[4] LinMTetal.Experientia, 1992;48(3): 225-22705
[5] LelisMetal.ActaMedPort, 1992;5(4):215-21806
[6] SukenikSetal.Harefuah, 1991; 121 (11):425-42907
[7] MichelHetal.PressMed, 1994;23 (10):479-48408
[8] HarthiSSetal.JInternMed, 1990;228(4):343-34609
[9] BiaryNetal. ClinNeurolNeurosury, 1995;97(1): 5510
[10] LinMTetal.BrainResBull, 1995;37(6):595-59811
[11] LinMTetal.AmJPhysiology,1995;269(38):H48712
[12] KaoTYetal.JApplPhysiology, 1996;80(2):680-68413
[13] SquireDL,PediatrClinNorthAm,1990;37(5):108514
[14] ShiehSDetal.Nephron, 1995;71 (4):428-43215
[15] 肖崇厚．中医诊断学，上海科技出版社，1987 121
[16] 雷载权．中药学，上海科技出版社，1992 140
[17] JimenezMME,MedClinBarc, 1990;94(13):481-48616
[18] YoungMSetal. ChinJPhysiol, 1993;36(4): 193-19804
[19] BiaryNetal.ClinNeurolNeurosury, 1995;97(1):5510
[20] LelisMetal.ActaMedPort, 1992;5(4):215-21806
[21] 刘志．气相色谱法测定麝香保心丸中麝香酮的含量 中国工药科大学学报[J] 1994，21(5)：213-215
[22] 崔文花，金美花．薄层—分光光度法测定中成药中麝香酮的含量 延边大学医学学报[J] 1995，21(1)；21—25
[23] 王应斌，李俊梅等．薄层扫描法测定蒙药嘎日迪-13 麝香中麝香酮的含量 中国民族医药杂志[J] 1996，12(1)；41—43
[24] 黄木春，陈万来等．用薄层扫描法测定熊胆中熊去氧胆酸和鹅去氧胆酸广东医学院学报[J] 1994，26(4)；254—255
[25] 刘卓妍，董元伟等．高效液相法测定蛇胆及蛇胆川贝液中牛磺胆酸的含
量 中成药[J] 1994，24(2)；124—125
[26] 张驰，彭会明等．熊脱氧胆酸的毛细管气相色谱法测定 中国医药工业杂志[J] 2000，27(11)：123—124
[27] 何念民，紫外分光光度法测定消溶胆石片中胆酸含量 中成药[J] 1995，25(1)：11—12
[28] 章辉，程光华等．老年肺心病缓解期患者血清甘胆酸测定的临床意义 中华老年医学杂志[J] 1995，12(4)；34—35
[29] 谢秀琼．中药新药制剂开发与应用 人民卫生出版社[J] 2000，12(9)；458
[30] 孙健人，王泰斌等．中暑的诊断与救治 实用乡村医生杂志[J] 199421(2)47—48
[31] 杜一民，胡本荣等．广霍香的化学成分及其药理作用研究进展 中药新药与临床药理[J] 1998，27(4)；78-79
[32] 张明发，莸琴等．干姜现代药理研究概述 中国是医药科技[J] 1996，24(2)；41—42
[33] 周宏雷，雷海民等．干姜挥发油的GC-MS分析 中国中药杂志[J] 1998，24(4)；26-27
[34] 任英，张名世等．两种不同色泽和质地的干姜质量比较 现代中药研究与实践[J] 1998，24(2)：134-135
[35] 曹春林．中药药剂学 上海科技出版社 1986 345
[36] 陈盐生，林玉莲等．干姜与炮姜挥发油成分比较 南京中医药大学学报[J]，1999，25{6}；45-47
[37] 杜一民，胡本荣等．广霍香的化学成分及其药理作用研究进展 中药新药与临床药理[J]，1998，21(4)；45-47
[38] 周名璐，陈芝喜等．霍香正气散的实验及临床研究进展 新中医[J]，1996，14(7)；56-58
[39] 罗明生．药剂辅料大全 四川科学技术出版社 1995；457
[40] 庄榆．吐温-80用于提高卡马西平片的溶出度 中国现代应用药学[J]，1995，14(5)；254-256
[41] 张恩娟，范开华等．氮酮及丙二醇对甲硝唑溶液体外经皮渗透性的影响
华西药学杂志[J]，1995，24(2)；241-243
[42] 陈振江，王绍芬等．表面活性剂的用法与测定 中国中药杂志[J] 1994，21(12)；234-235
[43] 尹士敏 王士贤等 麝香的药理作用及临床研究近况 天津药学[J] 2002，28(3)；265-267
[2] DahmashNSetal.Chest, 1993; 103(4): 1210-121403
[3] YoungMSetal.ChinJPhysiol, 1993;36(4): 193-19804
[4] LinMTetal.Experientia, 1992;48(3): 225-22705
[5] LelisMetal.ActaMedPort, 1992;5(4):215-21806
[6] SukenikSetal.Harefuah, 1991; 121 (11):425-42907
[7] MichelHetal.PressMed, 1994;23 (10):479-48408
[8] HarthiSSetal.JInternMed, 1990;228(4):343-34609
[9] BiaryNetal. ClinNeurolNeurosury, 1995;97(1): 5510
[10] LinMTetal.BrainResBull, 1995;37(6):595-59811
[11] LinMTetal.AmJPhysiology,1995;269(38):H48712
[12] KaoTYetal.JApplPhysiology, 1996;80(2):680-68413
[13] SquireDL,PediatrClinNorthAm,1990;37(5):108514
[14] ShiehSDetal.Nephron, 1995;71 (4):428-43215
[15] 肖崇厚．中医诊断学，上海科技出版社，1987 121
[16] 雷载权．中药学，上海科技出版社，1992 140
[17] JimenezMME,MedClinBarc, 1990;94(13):481-48616
[18] YoungMSetal. ChinJPhysiol, 1993;36(4): 193-19804
[19] BiaryNetal.ClinNeurolNeurosury, 1995;97(1):5510
[20] LelisMetal.ActaMedPort, 1992;5(4):215-21806
[21] 刘志．气相色谱法测定麝香保心丸中麝香酮的含量 中国工药科大学学报[J] 1994，21(5)：213-215
[22] 崔文花，金美花．薄层—分光光度法测定中成药中麝香酮的含量 延边大学医学学报[J] 1995，21(1)；21—25
[23] 王应斌，李俊梅等．薄层扫描法测定蒙药嘎日迪-13 麝香中麝香酮的含量 中国民族医药杂志[J] 1996，12(1)；41—43
[24] 黄木春，陈万来等．用薄层扫描法测定熊胆中熊去氧胆酸和鹅去氧胆酸广东医学院学报[J] 1994，26(4)；254—255
[25] 刘卓妍，董元伟等．高效液相法测定蛇胆及蛇胆川贝液中牛磺胆酸的含
量 中成药[J] 1994，24(2)；124—125
[26] 张驰，彭会明等．熊脱氧胆酸的毛细管气相色谱法测定 中国医药工业杂志[J] 2000，27(11)：123—124
[27] 何念民，紫外分光光度法测定消溶胆石片中胆酸含量 中成药[J] 1995，25(1)：11—12
[28] 章辉，程光华等．老年肺心病缓解期患者血清甘胆酸测定的临床意义 中华老年医学杂志[J] 1995，12(4)；34—35
[29] 谢秀琼．中药新药制剂开发与应用 人民卫生出版社[J] 2000，12(9)；458
[30] 孙健人，王泰斌等．中暑的诊断与救治 实用乡村医生杂志[J] 199421(2)47—48
[31] 杜一民，胡本荣等．广霍香的化学成分及其药理作用研究进展 中药新药与临床药理[J] 1998，27(4)；78-79
[32] 张明发，莸琴等．干姜现代药理研究概述 中国是医药科技[J] 1996，24(2)；41—42
[33] 周宏雷，雷海民等．干姜挥发油的GC-MS分析 中国中药杂志[J] 1998，24(4)；26-27
[34] 任英，张名世等．两种不同色泽和质地的干姜质量比较 现代中药研究与实践[J] 1998，24(2)：134-135
[35] 曹春林．中药药剂学 上海科技出版社 1986 345
[36] 陈盐生，林玉莲等．干姜与炮姜挥发油成分比较 南京中医药大学学报[J]，1999，25{6}；45-47
[37] 杜一民，胡本荣等．广霍香的化学成分及其药理作用研究进展 中药新药与临床药理[J]，1998，21(4)；45-47
[38] 周名璐，陈芝喜等．霍香正气散的实验及临床研究进展 新中医[J]，1996，14(7)；56-58
[39] 罗明生．药剂辅料大全 四川科学技术出版社 1995；457
[40] 庄榆．吐温-80用于提高卡马西平片的溶出度 中国现代应用药学[J]，1995，14(5)；254-256
[41] 张恩娟，范开华等．氮酮及丙二醇对甲硝唑溶液体外经皮渗透性的影响
华西药学杂志[J]，1995，24(2)；241-243
[42] 陈振江，王绍芬等．表面活性剂的用法与测定 中国中药杂志[J] 1994，21(12)；234-235
[43] 尹士敏 王士贤等 麝香的药理作用及临床研究近况 天津药学[J] 2002，28(3)；265-267