Study On The Inclusion Compound Of Tumor-targeting ——β-Cyclodextrin Sulfate

It has a long time that chemic remedy was used to cure the tumors.But,side-effect is a problem that when this method has been used. It isimportant to study the tumor-targeting dosage form for chemic remedy thatcan depress the side-effect and improve the curative effect. Study onadjuvant is a important side in studying the targeting dosage form andit has been a hotspot and nodus in the word。 According to the reports that β-cyclodextrin tetradecasufate(β-CD-S) is affinity to angiogenesis of tumors selectively. β-chclodextrin(β-CD) is inclusion compound carrier of drug in pharmacyand was used in lots of studying of dosage form, it will form a molecularcapsule. As the derivation of β-CD, theβ-CD-S has same structure withβ -CD. So β -CD-S is not only affinity to angiogenesis of tumorsselectively but also a inclusion compound carrier of drug. This disquisition synthesized the β-CD-S by the replacement ofpyridine salt with pyridine trioxide. IR: β-CD-S is more two apexes(2099cm-1, 1644 cm-1) than β-CD and no apex remove。1HNMR: The districtof 3.8-4.37ppm is the all signal of H-1 of glucose except extremity H-1;The district of 4.5-5.6ppm is the all signal of extremity H-1. ESI-MS( m\z):1810.94,1577.54,1426.92,1354.96,1304.03,1252.94,1202.06,the otheris attribute to isotope. The difference of m\z between 1354.96 and1252.94,1304. 03 and 1202.06 is 102,it is attribute to the H replacedby -SO2Na. These distributing of m\z is attribute to β-CD that isesterified by sulfate. The analysis of element: C(18.45%);H(45%);S(15.55%). It is testified that the substance is β -chclodextrintetradecasufate(β-CD-S). 4This disquisition has studied the toxicity of β-CD-S. The result ofthe acute toxic experiment showed that the LD50 of β-CD-S to the micestomach clysis was more than 10000mg/kg. The result of 30 day's feedingexperiment of rat showed that the general behave,the quantity of eat,the gaining weight,the value in use of eat,the value of haematology,the value of serology and the weight value of innards have no remarkablevariety by contrast the test groups to collator of rat. The result ofpathology anatomize showed that the heart,liver,lung,spleen,kidneyand germ apparatus of every group rats have no abnormity. This disquisition has studied the inclusion complex of anti-tumorsdrug withβ-CD-S used Fluorouracil and Methotrexate as model drug. Thefactors affecting inclusion complex were studied with orthogonal designtest. The experiment showed that the optimize process of Fluorouracil isthat the inclusion complex should be formed in aqueous solution contain15% β-CD-S, in water bath 60℃ for 60min,and that the optimize processof Methotrexate is that the inclusion complex should be formed in aqueoussolution contain 15% β-CD-S, in water bath 80℃ for 90min.The DTA thermograms showed that in β -CD-S inclusion complex, Fluorouracil andMethotrexate existed as minor crystalline. The result of resolvableexperiment showed that the solubility of was increased by theconcentration increased ofβ-CD-S, and be linearity. The solubility of50%(W/V) Fluorouracil and Methotrexate in 50%(W/V) β-CD-S is 12.6times and 121.2 times more than raw drug. The K of β-CD-S inclusioncomplex Fluorouracil and Methotrexate are 17.14 and 404.5. The high performance liquid chromatographic (HPLC) method using UVdetector was adopted for the determination of Fluorouracili in rat liver.The standard curve was linear in the range of 0.5-20μg·ml-1(r=0.9997);The results showed good recovery (>98%); and high precision (RSD<5%). The rat liver cancer model was established by the inducement of 5diethylnitrosamine (DENA). The tumor grew up obviously in rats by theobserving of tissue slice and CT of liver. The A/G,ALT,AST,γ-GT,ALP and BIL of testing rats are more than blank's obviously(P<0.01) whilethe ALB,PT were no varie...