| Tanreqing (TRQ) is an optimized prescription based on Shuanghuanglian and Qingkailing, which consists of five Chinese herbs:Scutellariae Radix(HQ), Fel Selenarcti(XDF), Cornu Naemorhedi(SYJ), Flos Lonicerae(JYH) and Forsythiae Fructus(LQ). In this prescription, Scutellariae Radix is regarded as monarch drug, Fel Selenarcti and Cornu Naemorhedi as minister drug, honeysuckle as adjuvant drug, forsythia as guide drug. TRQ has the effect of clearing heat and removing toxicity as well as keeping calm and relieving convulsion, so it can be used to treat upper respiratory infection, acute pneumonia, acute bronchitis and ect. The clinical application of TRQ injection is wide and shows its remarkable curative effect, but the method of administration is limited and dangerous. Hence studying the oral preparations of TRQ is to become inevitable.This paper verifies the drug action of TRQ capsules. Then we study the oral absorption effect of chlorogenic acid which is the active ingredient of JYH in TRQ. And we evaluate the feasibility of developing TRQ multi-component, in order to provide a studying basis of illuminating the oral absorption mechanism of TRQ and developing preparation of TRQ multi-component.This paper includes four parts:1 Study on the major pharmacodynamics of TRQ capsulesContrasting to TRQ injection, we select xylene-induced mouse ear edema model, acetic acid-induced writhing models and hotplate-induced pain model, in order to study the anti-inflammatory and analgesic efficacy of TRQ capsules. Results show that TRQ capsules have significant inhibition on xylene-induced rats’ears swelling (P<0.05). Meanwhile, low concentration and high concentration show equal inhibition of rats’ears swelling. Inhibition rate does not increase when dose increases. TRQ capsules have significant inhibition on acetic acid-induced rats writhing and hotplate-induced rats pain (P<0.05). And the high dose has more significant inhibition (P<0.01), which shows that the inhibition was correlated with dose. The above conclusions show that TRQ still has a certain effect when changing administration route from intravenous into oral, and the effectiveness and safety of clinical medication is even more guaranteed. Thus provide a theoretical basis for studying the oral absorption mechanism of TRQ in future.2 Effects of drug compatibility of TRQ on the pharmacokinetics of chlorogenic acid in ratsHPLC quantitative analysis method for chlorogenic acid biological samples is established, so as to study the effects of drug compatibility of TRQ on the pharmacokinetics of chlorogenic acid in rats. Compared with Zuo, the content of chlorogenic acid are all reduced in other groups, but the differences of pharmacokinetic parameters aren’t significantly. But t1/2z, Cmax, Vz/F of Quanfang are significantly reduced (P<0.05). It is indicated that Quanfang relatively inhibited the absorption of chlorogenic acid in rats, delayed its elimination in body, and increased its duration of action in vivo. To analyze the reasons, chlorogenic acid may bind with efflux proteins competitively and impede its own absorption, so as to promote the absorption of other medicinal ingredient and make TRQ play better efficacy.3 The intestinal Absorption Mechanism of chlorogenic acid in situ single pass intestinal perfusion modelIn situ single pass intestinal perfusion model was built to analyze the intestinal absorption mechanism of chlorogenic acid. The results showed that chlorogenic acid can be absorbed in different sections of small intestine (duodenum, jejunum and ileum) as well as colon. The order of Ka is colon> ileum> duodenum> jejunum, the order of Peff is ileum> colon> duodenum> jejunum. It can be known from experiments that chlorogenic acid can be absorbed in all sections of intestine without special section. Quanfang group has a considerable number of chlorogenic acid hydrolyzed into other ingredients, which might be result of the interaction of components, promoted hydrolysis inside guts, existed in the form of metabolites in the intestines, thus inhibiting the absorption of chlorogenic acid. Or may be chlorogenic acid binds with efflux proteins competitively and promote the absorption of other medicinal ingredient.4 Study on pharmacodynamics of TRQ multi-componentSelect xylene-induced mouse ear edema model and hotplate-induced pain model, in order to study the anti-inflammatory and analgesic efficacy of TRQ multi-component, and evaluate its druggability. Results showed that all groups don’t show significant inhibiting effect on xylene-induced rats’ ear swelling (P>0.05). Meanwhile, it shows significant inhibition of pain in rats (P<0.05), but low dose has no difference from high dose (P>0.05), which shows that the inhibition of rats pain was uncorrelated with dose.In summary, this paper confirms the anti-inflammatory and analgesic efficacy of TRQ capsules. Then study the oral absorption of chlorogenic acid in TRQ, infer that chlorogenic acid exists in the form of metabolites in the intestines, or it binds with efflux proteins competitively and promote the absorption of other medicinal ingredient. To study on pharmacodynamics of TRQ multi-component, the results show that the TRQ multi-component has no significant inhibiting effect on xylene-induced rats’ ear swelling, but has significant inhibition of pain. It provide a further route of optimizing the extracting and purifing process, screening the compatibility and its proportion of TRQ. |
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