Bioactive Materials Preparation And Characterization Of Platinum Complexes

Platinum-based composition materials play a very important role in many fields such as homogeneous catalyzing of petrochemical industry, fine chemical industry and energy sources etc. Cancer therapy is a case application of platinum-based composition, which forms a very important component of cancer therapeutic drugs, and it has an irreplaceable position. At present, Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Sunplatin, Lobaplatin and Miriplatin are platinum-based materials clinically used in anti-cancer drugs, among which the previous three types are widely used in the whole world, while the latter four types are permitted to being used only in several countries.Great successes have been made in applying these compositions to the clinical usage, but their defects such as serious side-effect, numbered anti-cancer spectrum, and their mutual cross-resistant prevent them from being extensively used. Because of the success and the defects of Cisplatin, Carboplatin, platinum-based composition materials are still one of the attractive investigations anti-tumour drugs home and abroad. Such researches are generally focused on the traditional chemical-structured platinum compounds, oral Pt(IV) compounds, sterically hindered Pt compounds, trans-structure Pt compounds and multi-nuclear Pt compounds. The main research contents are as follow:1. The systemic researches have been done on the pharmic materials of Satraplatin (Cis-dichloro-bisaceto-cis-Amminecyclohexanea-mineplatinum(IV)) under the national regulations and the guideline of drug registration, including the preparation techniques, characterization, analysis method, physic-chemo properties and stability features of Satraplatin. The results showed that the acquired preparation techniques of Satraplatin are of high stability, fidelity and product purity. Modern analysis methods such as Element assay(EA), Ultraviolet(UV), Infrared(IR), Nuclear magnetic resonance(NMR), and mass spectrum(MS) were used to characterize the chemical structure of Satraplatin, and the results were consistent with the theoretical ones. The high performance liquid chromatogram(HPLC) analysis method of Satraplatin has been formed. Quality criterion(draft) of Satraplatin has been framed by the results of its physic-chemo properties, identification, analysis method and stability research. 2. Through researches, preparation recipe of Satraplatin capsule has been formed; the dissolution rate, analysis method, physic-chemo properties and stability of Satraplatin capusale have been tested, forming the HPLC analysis method of Satraplatin capsule and framing the quality criterion(draft) of Satraplatin capsule.3. This paper researched on the primary pharmacodynamics, acute toxicity, general pharmacology, gene toxic, carcinogenic and teratogenicity test, long-term toxicity of Satraplatin under the reference guideline. MTT method was used to test the in-vitro cell-line inhabitation of Satraplatin. The result showed that the human ovarian carcinoma cell-line(A2780), human colorectal carcinoma cell-line(HCT-8), human oral epithelium carcinoma cell-line(KB), human lung-cancer cell-line(A549) were inhibited obviously. The in-vivo carcinoma inhabitation test confirmed that Satraplatin could inhibit the mice Xenograft of S180 and Heps. The test methods showed that the neoplasm inhibiting ability of Satraplatin and Cisplatin are similar, and Satraplatin is a kind of orally active platinum anti-cancer drugs. LD50 of Satraplatin is 280.7 mg/kg for ICR rat by the oral route. The results of general pharmacology showed that Satraplatin does not affect blood pressure, breath, cardiogram of cats and mice. Researches have been done on the long-term toxicity of oral administration of Satraplatin by using the SD rats, and the results showed that the innocuity dose is 10mg/kg, and 20mg/kg is the low-grade toxicity dose. The result of gene toxic showed that Satrapltin could induce mutation of TA mice typhoid mutating salmonella cell-line. The results of carcinogenic showed that under this testing condition, Satraplatin acted on the mice medullla micro nucleus is positive. The result of Satraplatin composition inducing aberration sensitive period toxicity test showed that 5mg/kg, 10mg/kg Satraplatin appeare nontoxic for intragastric administration of pregnant mice, while 20mg/kg Satraplatin induced a decrease of ingestion amount and obviously affected their weight(P<0.05). The research showed that in this test condition, Satraplatin composition materials do not have potential aberrance to the SD rat and the minimum dose of embryo toxicity is 5mg/kg. To test the total platinum concentration of Satraplatin in the rat by atom-absorbing spectrum, the fitting result of plasma drug-time curve is extra-vascular administration of primary absorbance double-chamber model. 4. The sterically hindered Pt(â…¡) composition materials are one of the primary research directions in platinum-based anti-tumor drug domain in the whole world. This paper discussed the preparation method of Picoplatin (Cis-amminedichlorornethylpyridineplatIn-um(â…¡)) and its analogs. Modern analysis methods such as Element assay(EA), Ultraviolet(UV), Infrared(IR), Nuclear magnetic resonance(NMR) and Mass spectrum(MS) were used to characterize their chemical structures, the result was consistent with the theoretical ones. The elementary tumor cell-line inhabitation test result showed that Picoplatin and its analogs possess anti-tumor activity.