Nitric oxide-donating non-steroidal anti-inflammatory drug β-cyclodextrin or its derivative inclusion compound and its preparation method and use

Abstract

The invention provides a nitric oxide donor non-steroidal anti-inflammatory drug β-cyclodextrin or its derivative inclusion compound and a preparation method thereof. The inclusion compound of the nitric oxide-donating non-steroidal anti-inflammatory drug β-cyclodextrin or its derivatives contains a nitric oxide-donating non-steroidal anti-inflammatory drug and a β-cyclodextrin or a derivative of a β-cyclodextrin The molar ratio of nitric oxide-donating non-steroidal anti-inflammatory drugs to β-cyclodextrin or β-cyclodextrin derivatives is 1:1 to 1:25. The clathrate has high bioavailability and good stability. The preparation method of the clathrate provided by the invention realizes the complete separation of the clathrate and the unincluded raw material drug, and the unincluded raw material drug can be completely recovered, thereby reducing the cost. The inclusion rate of the preferred preparation method can reach more than 70%.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a nitric oxide donor type non-steroidal anti-inflammatory drug β-cyclodextrin or a derivative inclusion compound thereof, a preparation method and application thereof. Background technique [0002] Since S. Dentin successfully obtained β-cyclodextrin (β-CD) from the fermentation broth for the first time in 1903, researchers have made great progress in the preparation, properties and applications of cyclodextrin, especially in the past two or three years. In the past ten years, the application of cyclodextrin and its derivatives in the pharmaceutical industry has attracted much attention. Drug cyclodextrin inclusion complexes have increasingly shown unique properties and application values ​​in improving drug solubility, dissolution rate, and bioavailability. In recent years, cyclodextrin inclusion technology has become an effective means to enhance the bioavailabili...

AI Technical Summary

Problems solved by technology

Using the above two methods, although it is possible to carry out cyclodextrin inclusion of nitric oxide-donating NSAIDs, there are still some technical difficulties

First, nitric oxide-donating NSAIDs are solid or oily liquids that are poorly soluble in water. In the above two methods, before separation, the clathrates prepared are mixed with the unincluded nitric oxide-donating Non-steroidal anti-inflammatory drugs co-exist in the inclusion system, oily or solid unincluded drugs and inclusion complex solids are prone to sticking, separation is difficult, let alone recycling, so large-scale production cannot be realized

Second, the unincluded drug sticks to the inclusion compound, and it is difficult to separate completely, resulting in a decrease in the uniformity of the inclusion compound, which in turn affects the accuracy of feeding the preparation, resulting in poor druggability, poor stability of the preparation, and poor dissolution of solid preparations, etc. question

Third, using the above two existing technologies, the encapsulation efficiency is low; in order to improve the encapsulation efficiency of nitric oxide-donating NSAIDs, it is necessary to greatly increase the amount of cyclodextrin used

Too low drug loading is not suitable for preparation production

Because: too low drug loading leads to an increase in the amount of inclusion compound in the preparation, which increases the cost; too low drug loading also makes the quality or volume of the unit preparation too large, causing inconvenience in use and reducing patient compliance

Images