| "Siwei Tumuxiang San",also known as Chagan Decoction,is composed of four herbs coarse powder of Tumuxiang,Sophora flavescens,Rubus sylvestris,and Shantou in a ratio of4:4:2:1 and has the function of clearing temperature and resolving the table.It is a classic prescription for Mongolian medicine to treat blast fever.The research team conducted the separation and identification of the chemical components in vivo and in vitro and the activity study in the early stage.The results showed that"Siwei Tumuxiang San"has anti-inflammatory,analgesic,antibacterial and immunomodulatory activities,and its medicinal material basis may be derived from There are no reports on the pharmacokinetics of the main components in the compound prescriptions in Sophora flavescens and Inulin.This article selects four main components from the compound prescriptions to study the pharmacokinetics and clarify the main components in the prescriptions.The in vivo pharmacokinetic process of medicinal ingredients.Objective:To use triple quadrupole mass spectrometer and ultra-high performance liquid chromatograph to study the pharmacokinetic process of the four main components of"Siwei Tumuxiang San"in healthy rats,and to clarify the monomers The difference in pharmacokinetics of the main components in animals after the compound administration of the ingredients and the"Siwei Tumuxiang San"compound provides a reference for the rationality and safety of the clinical use of the"Siwei Tumuxiang San".Methods:1)Prepare"Siwei Tumuxiang Powder"administration samples,and use inulin（AL）,isoinulin（IAL）,matrine（M）,and oxymatrine（OM）as detection Index,use high performance liquid chromatography（HPLC）to determine the content of 4 main components in"Siwei Tumuxiang San".2)Thirty healthy Wistar male rats were randomly divided into 5 groups,which were intragastrically administered inelenolactone group（180 mg/kg）,isoelenoterolactone group（165 mg/kg）,and were administered by tail vein injection.Inulin-lactone group（25 mg/kg）,iso-inulin-lactone group（25 mg/kg）and gavage"Siwei Tumuxiang San"group（11.6 g/kg）,after administration,use ultra-high performance liquid Chromatography-tandem mass spectrometry（UPLC-MS/MS）method was used to determine the plasma concentrations of inulin and iso-inulin at different time points,and DAS 2.0 software was used to calculate the pharmacokinetic parameters.3)Thirty healthy Wistar male rats were randomly divided into 5 groups,namely the matrine group（16.6 mg/kg）and oxymatrine group（46.6 mg/kg）administered by gavage.Matrine was administered by tail vein injection.Alkaline group（16.6 mg/kg）,oxymatrine group（46.6 mg/kg）and intragastric administration"Siwei Tumuxiang San"group（11.6 g/kg）,after administration,use ultra high performance liquid chromatography-Tandem mass spectrometry（UPLC-MS/MS）method was used to determine the plasma concentrations of matrine and oxymatrine at different time points,and DAS 2.0 software was used to calculate the pharmacokinetic parameters.Results:1)Pharmacokinetics of elegans lactone:both the compound and single administration of elegans lactone conformed to the two-compartment model.When the monomer is administered orally,the distribution half-life t1/2αof elegans lactone is 0.25±0.31h,the elimination half-life t1/2βis 0.60±0.04 h,and the area under the curve AUC（0-∞）is297.39±99.94 ng/L*h,the maximum blood concentration Cmax is 454.51±165.61 ng/L,and the absolute bioavailability（Fc）is 3.39%.When the compound"Siwei Tumuxiang San"is administered,the distribution half-life t1/2αof Inulin is 0.19±0.04 h,the elimination half-life t1/2βis 0.31±0.03 h,and the area under the curve AUC（0-∞）is 2498.74±584.04 ng/L*h,the maximum blood concentration Cmaxis 1332.53±346.30 ng/L,and the absolute bioavailability is 28.48%.Compared with single drug administration,t1/2αand t1/2βare shortened in compound administration,and CL/F is slowed down,indicating that the distribution and elimination of elegans lactone in the body is slowed down;the rest show an increasing trend,among which tmax,AUC and Cmax In order to be significant,it indicates that the drug exposure in the body has increased,and the Fc has increased by 8 times.2)The pharmacokinetics of isoinulin:both the compound administration and the monomer administration of isoinulin are in line with the two-compartment model.When the monomer is administered orally,the elimination half-life t1/2βof isoinulin is 0.31±0.04 h,the apparent volume of distribution V1/F is 4509.88±3461.65 L/kg,and the retention time in vivo MRT（0-∞）is 4.99±2.37 h,the absolute bioavailability is 3.39%.When the"Siwei Tumuxiang San"compound is administered,the elimination half-life t1/2βof isoinulin is 0.21±0.11 h,the apparent volume of distribution V1/F is 12874.86±16049.29 L/kg,and the retention time in the body is MRT（0-∞）is 2.62±0.67 h,and the absolute bioavailability is2.86%.Comparing the compound administration with the monomer administration,except that t1/2βand MRT decreased,the others showed an increasing trend.Among them,Tmax and V1/F were significantly increased.The absolute bioavailability of isoinulin in the compound Fc was 2.86%,a year-on-year increase of 3 times.3)The pharmacokinetics of matrine:both the compound and single doses of matrine conform to the two-compartment model.When the monomer is administered orally,the distribution half-life t1/2αof matrine is 1.05±0.36 h,the area under the curve AUC（0-∞）is7334.73±3411.68 ng/L*h,and the retention time in vivo is MRT（0-∞）It is 6.03±1.36 h,and the absolute bioavailability is 42.95%.When the compound"Siwei Tumuxiang San"is administered,the distribution half-life t1/2αof matrine is 5.19±1.91 h,the area under the curve AUC（0-∞）is 26055.66±8364.00 ng/L*h,and the retention time in the body is MRT（0-∞）is 14.62±2.04 h,and the absolute bioavailability is 84.26%.Compared with single drug administration,compound administration increased t1/2α,t1/2β,MRT,AUC,Cmaxand tmax,and decreased in vivo clearance.Among them,T1/2α,AUC and CL/F were statistically significant,Fc can be increased from 42.95%to 84.26%,which is twice the original bioavailability.4)The pharmacokinetics of oxymatrine:both oxymatrine compound administration and single administration are in line with the two-compartment model.When the monomer is orally administered,the distribution half-life t1/2αof oxymatrine is 0.56±0.228 h,the area under the curve AUC（0-∞）is 7600.07±476.80 ng/L*h,and the retention time in vivo is MRT（0-∞）Is 3.14±0.597 h,the peak time tmax is 1.04±0.40 h,and the absolute bioavailability is7.33%.The conversion rate of oxymatrine to matrine during oral administration was 49.09%,and the conversion rate of oxymatrine to matrine during tail vein injection was 28.90%.When the compound"Siwei Tumuxiang San"is administered,the distribution half-life t1/2αof oxymatrine is 0.39±0.25 h,the area under the curve AUC（0-∞）is 3396.28±1085.03 ng/L*h,and the retention time in the body The MRT（0-∞）is 5.75±0.74 h,the peak time tmax is 0.58±0.25 h,and the absolute bioavailability Fc is 84.26%.Compared with the single administration,the compound administration has reduced t1/2α,CL/F,AUC and Tmax.The Fc of compound oxymatrine is 3.09%,which is 0.5 times lower.The conversion rate of oxymatrine to matrine in the body of intragastric administration was 49.09%,which was 1.7times that of the tail vein injection of oxymatrine.Conclusion:1)Inulin and iso-inulin:Compared with the monomer intragastric administration,the pharmacokinetic processes of AL and IAL in healthy rats are significantly different in the compound administration group.Compound administration not only prolonged the retention time in the body,but also increased the amount of drug exposed to the body,and the bioavailability was significantly increased.Inulin is more obvious,which proves that the reasonable compatibility of"Siwei Inulin powder"makes Inulin Better play the role of anti-inflammatory and immune regulation.2)Matrine and oxymatrine:Compared with single intragastric administration,the pharmacokinetics of M and OM are different in the compound administration group.Especially matrine is more significant.After compound administration,it can slow down the metabolic rate,prolong the retention time in the body,and have a higher total bioavailability.It is beneficial to its anti-inflammatory and immunomodulatory effects in the body,but it may also bring toxic side effect.In summary,this article established a UPLC-MS/MS method for the in vivo quantification of the four main components of"Siwei Tumuxiang San",combined with monomer administration,and explored the pharmacokinetic characteristics of the four main components after compound administration.The change of"Siwei Tumuxiang San"provides a certain basis for the rationality and safety of clinical medication. |
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