Hemolytic And Renal Toxicity Of The Inclusion Complex Of Sulfobutyl-?-Cyclodextrins With Different Degrees Of Substitution

SBE-?-CD as a new kind of medicinal material,has the incomparable advantage of other cyclodextrin derivatives.SBE-?-CD in the body without association,with the prototype by the rapid excretion of urine,close to the glomerular filtration rate,mainly distributed in the extracellular fluid and Low binding to plasma proteins.In the hemolysis test,SBE-?-CD was found to be far less than beta cyclodextrin,Hemolytic rate and degree of substitution are related,With the increase of degree of substitution,the effect of hemolysis decreased.And SBE-?-CD renal toxicity is low,BUN Detection discovery,SBE5-?-CD mice BUN data with physiological sodium chloride solution group showed no significant difference,Pathological examination revealed that there was no renal damage in SBE5-?-CD.Urinary excretion research have found that the SBE₁-?-CD is far faster than the ?-CD,The reason may be that in the molecular structure of the SBE₁-?-CD,there are a lot of sulfonic acid groups in the molecular structure,which lead to the reduction of heavy absorption,Reduction in urinary excretion.Rabbit conjunctivaand and corneal non toxic reaction with SBE-?-CD;And HP-?-CD compared to the nasal mucosa stimulation is smaller.Animal acute and subacute experimental findings Oral SBE-?-CD is safety for human.Muscle injection with no or only mild stimulation.Therefore,the study on the hemolytic and renal toxicity of the drugs which are used as the supplementary materials will provide the theoretical basis for the selection of more safe and reliable drug materials.Preparation of inclusion compound of SBE-?-CD: TMP,ciprofloxacin,phenytoin,SG the 4 drugs as raw materials,Mainly uses the saturated solution method,use ultrasonic clathration,Molar ratio: TMP/SBE₁-?-CD 2:1,TMP/SBE₄-?-CD 2:1,TMP/SBE₇-?-CD3:2.Dil/SBE₁-?-CD 3:1,Dil/SBE₄-?-CD 1:1,Dil/SBE₇-?-CD 2:1.SG/SBE₁-?-CD2:1,SG/SBE₄-?-CD 2:1,SG/SBE₇-?-CD 3:1.CIP/SBE₁-?-CD 3:1,CIP/SBE₄-?-CD3:1,CIP/SBE₇-?-CD 1:1Hemolysis: Red blood cell rupture,hemoglobin escape called red blood cell lysis,referred to as hemolysis,It can be caused by physical,chemical factors or toxins.In view of its relationship with the drug itself,In order to investigate the safety of injection,Reference to the "Chinese Pharmacopoeia" 2010 edition of the application of the guiding principlesof safety inspection,Using conventional in vitro test tube method?naked eye observation?and improved in vitro hemolysis test method?spectrophotometry?to detection hemolysis rate of inclusion compound,In general,To cause hemolysis or agglutination in 30 min that should not be used for injection.Renal toxicity: The kidney is an important organ of drug metabolism and excretion,renal damage caused by drugs is increasing,mainly for renal toxicity and allergic reaction.In order to improve the safety and quality of medicine,I make a renal toxicity text.method:50 mice were randomly divided into 5 groups,each with 10,respectively,number 1.2.3.4.5.1 for the normal control group,?Saline injection 20ml/kg?,2 for raw material drug group,3,4,5 for inclusion complex group,through inwaperitoneal injection for 7 days.Using automatic biochemical analyzer to detect BUN,Cr.Anatomy of the kidney,Calculate the weight coefficient of kidney.If there is kidney damage in mice,HE staining was used in histopathology.This study is mainly for the determination of trimethoprim,ciprofloxacin,phenytoin,sulphaguanidine these 4 drugs using sulfobutylether beta cyclodextrin inclusion,by hemolytic test,determine the inclusion of whether it can be used with intravenous injection,and through the comparison of different degree of substitution.Determine the safety in Hemolytic differences of reliable inclusion.In the kidney toxicity test to determine the inclusion of non-toxic side effects of drugs and the influences of different degrees of substitution on renal toxicity.In order to provide a theoretical basis for the future use of sulfobutyl-?-cyclodextrins more safe and reliable as the ultimate goal.