Detection Of Osmotic Pressure And Insoluble Particulates Commonly Used In Clinical And Its Safety To Lung Tissue Of SD Rats

OBJECTIVE: To explore the safety of atomization of non atomized dosage forms and its influencing factors By detecting The p H value,osmotic pressure,insoluble particles of the commonly used clinical atomization solution and observing the pathological changes of the lung tissue of the rats.Methods: According to the variety and concentration of the reported atomizing solution,we prepared saline(0.9% sodium chloride),silica(40mg / ml),Dingchuan decoction,Danshen,Shuanghuanglian,Qingkailing,Tanreqing,ceftriaxone(200mg / ml),gentamicin(16000 U / ml),budesonide(0.1mg / ml)and salbutamol(1mg / ml).The p H value,osmotic pressure concentration and the number of insoluble particles in each solution were measured.60 SPF healthy male SD rats were randomly divided into 12 groups,5 rats in each group,which were blank control group,normal saline group,silica group,Dingchuan Decoction group,Danshen group,Shuanghuanglian group,Qingkailing group,Tanreqing group,ceftriaxone group,gentamicin group,budesonide group and salbutamol group,with the same concentration.The rats in each group were atomized with 10 ml of the corresponding solution twice a day for 30 minutes for 56 days.After atomization,SD rats were uniformly sacrificed.Lung tissue of the middle lobe of the left lung was cut and stained with HE to observe its histopathological changes and count the number of dust cells.Put the above data into database for statistical data analysis.Results: 1.PH value test of drug solution: The PH value of the test drug ranges from 4.3 to 7.9,the highest of which is Tanreqing group,which is alkaline;the lowest of salbutamol group,which is acidic.2.Test of osmotic pressure of medicinal solution: The osmotic pressure of medicinal drugs ranges from 138 to 1803 m Osm.The osmotic pressure of Tanreqing group is the highest,and Dingchuantang group is the lowest.3.Detection of insoluble particles in the drug solution(PM1.0 ～ 2.5;PM2.5 ～ 5.0;PM5.0 ～ PM10;> PM10): The drugs in each group are quite different,and the insoluble particles contained in the albuterol group are between PM1.0 ～ 2.5,PM2.5 ～ 5.0,PM5.0 ～ PM10,and> PM10 are the least in the four ranges,and the insoluble particles contained in the silica group have the most insoluble particles in each range.Dingchuan soup and budesonide follow closely behind them.Later,while the Dingchuan Decoction group was more than PM10,the budesonide group showed a significant performance in the range of PM1.0-5.0.4.Pathological changes and dust cell counts in lung tissue sections: Sections of the blank control group,saline group,salbutamol group and budesonide group showed that the physiological structure of the lung tissue was intact,the thickness of smooth muscles in the bronchial tube wall was uniform,and the interstitial lung was not seen or rare Inflammatory cell infiltration;the antibiotic group(gentamicin group,ceftriaxone group)and the Chinese medicine preparation group(dingchuan decoction group,salvia group,Shuanghuanglian group,Qingkailing group,Tanreqing group)were all different The degree of lung tissue destruction,alveolar wall thickening,pulmonary interstitial edema,and inflammatory cell infiltration were visible,and the number of dust cells distributed in the alveolar cavity and the pulmonary interstitial space was different.Among them,Dingchuan Decoction showed the most obvious performance;the silicon dioxide group showed lung tissue The structure is disordered,the thickness of the interstitial lung is different,and some alveoli are congested,and more dust cells and a large number of inflammatory cells infiltrate.Pulmonary dust cells had the highest on silica and the lowest salbutamol.5.Statistical analysis: The results show that the correlation between drug PH,drug osmotic pressure and dust cell count is not significant;PM1.0 ～ 2.5 has a significant positive correlation with dust cell count.CONCLUSION: There is no obvious lung tissue damage when inhaled by normal saline,budesonide,and salbutamol.Long-term nebulization of saline,salbutamol,and budesonide did not cause pathological changes in the lung tissue of SD rats;inhalation of ceftriaxone,gentamicin,traditional Chinese medicine preparations,and silicon dioxide could cause lung damage to SD rats Tissue damage.This damage may be related to the high osmotic pressure and high insoluble particles of the nebulized drug solution.It should be administered according to the route specified in the drug instruction manual.It is not recommended to use non-atomized nebulized inhalation when its safety is not clear treatment.