Nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as preparation method and application thereof

Abstract

The invention provides a nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as a preparation method and an application thereof. The nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound comprises a nitric oxide donor type non-steroidal anti-inflammatory drug and beta-cyclodextrin or a beta-cyclodextrin derivative, wherein the molar ratio of the nitric oxide donor type non-steroidal anti-inflammatory drug to beta-cyclodextrin or the beta-cyclodextrin derivative is 1: 1-1: 25. The inclusion compound has high bioavailability and good stability. The preparation method of the inclusion compound, provided by the invention, has the advantages that that the complete separation of the inclusion compound from medicinal raw materials which are not included is realized, the medicinal raw materials which are not included can be completely recycled, and the cost is reduced. The inclusion rate of the preferable preparation method reaches above 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

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