Preparation method for beta-cyclodextrin polymer-paclitaxel inclusion compound

Abstract

The invention relates to a preparation method for beta-cyclodextrin polymer-paclitaxel inclusion compound, and belongs to the technical fields of supermolecule inclusion and water-soluble drug preparing. According to the present invention, the beta-cyclodextrin and epichlorohydrin are subjected to a cross linking reaction under a strong alkaline condition to generate a beta-cyclodextrin polymer; then N,N-dimethylformamide is adopted as a reaction solvent, the beta-cyclodextrin polymer and the paclitaxel are subjected to a homogeneous supermolecule reaction to generate the beta-cyclodextrin polymer-paclitaxel inclusion compound; after completing the reaction, a precipitation agent is added to precipitate the solid; after carrying out sucking filtration, the resulting filter cake is washed with dehydrated alcohol, and is placed in an environment having a temperature of 30-50 DEG C to carry out vacuum drying to obtain the beta-cyclodextrin polymer-paclitaxel inclusion compound. According to the present invention, the operation is simple; the conditions are easy to be controlled; the product purity can be 95-98%; the product has excellent water solubility and stable structure; the structure and the pharmaceutical characteristic of the paclitaxel are not destroyed, such that the natural anti-cancer drug of the paclitaxel with poor water solubility is expected to be made into the oral drug or intravenous injection.

Description

technical field [0001] The invention belongs to the technical field of preparation of water-soluble drugs in the technical field of supramolecular inclusion. Background technique [0002] As the second-generation supramolecular main compound—cyclodextrins (CDs for short), a class of cyclic oligosaccharides composed of more than 6 D-glucopyranose units bonded by a-1,4, According to the number of glucose units it contains, it can be divided into a-CD, b-CD and g-CD, etc. Among them, b-cyclodextrin (b-CD) has the highest yield, the cheapest price and the most widely used. The characteristic of cyclodextrin compounds is that they all have a certain size of hydrophobic cavity, so they can selectively include various types of guest molecules to form supramolecular compounds. Due to its unique structure, both theoretical research and practical application of cyclodextrin have been developed rapidly. It has important uses in industry, agriculture, food, medicine, separation techno...

AI Technical Summary

Problems solved by technology

[0007] 1. According to literature reports, cyclodextrin and paclitaxel form a 2:1 supramolecular inclusion complex, that is, two cyclodextrin molecules wrap one paclitaxel molecule. Therefore, common cyclodextrin derivatives have limited inclusion ability for paclitaxel. The inclusion reaction is difficult to carry out, the inclusion constant is small, and the range of solubility increase of the obtained supramolecular inclusion compound is also limited

At the same time, the stability of the obtained supramolecular clathrate is limited to a certain extent.

[0008] 2. During the preparation process, in order to wrap the drug in the cyclodextrin cavity as much as possible, the amount of the main compound is often much greater than the amount of the drug (the mass ratio of the main compound to the drug is 10-150:1), resulting in the final The product contains a large number of main compounds, which cannot guarantee the purity of the inclusion compound, which will affect the determination of the drug concentration in the next step. At the same time, excessive main compounds will also cause certain damage to human organs

[0009] 3. The supramolecular clathrate was prepared by the mixed solvent method, because the solubility of paclitaxel in water is very small (about 0.006 mg·mL -1 ), in the mixed solvent, there will still be part of paclitaxel that cannot be dissolved, and the inclusion reaction is not carried out in a homogeneous system. On the one hand, the inclusion reaction cannot be fully carried out, and the yield is low; on the other hand, after the inclusion reaction It is necessary to filter the reaction system with a microporous membrane to remove the unreacted or dissolved paclitaxel, which causes waste of the original drug paclitaxel and increases the production cost

Images