Chitosan-chitosan derivative nanosphere for loading indissoluble medicament, preparation method of nanosphere, and application of nanosphere serving as oral prepration

Abstract

The invention provides a chitosan-chitosan derivative nanosphere product for loading an indissoluble medicament. The product has a porous structure with controllable aperture, thus being capable of controlling the medicament to be released relatively quickly and stably. When the nanosphere product is taken as an oral preparation, as a large number of positive charges exist on the surface of the nanosphere product, the adhesiveness and membrane permeability of the preparation on a small intestine part are improved greatly, and the oral bioavailability of the medicament is enhanced. Simultaneously, the product can be jointly loaded with medicaments with electronegativity or coupling targeting ligands to achieve the aim of coordinating administration or targeting administration. The chitosan-chitosan derivative nanosphere product not only can be used for improving the tolerance of a patient, but also has relatively low toxic and side effects. The invention also provides a preparation method of the chitosan-chitosan derivative nanosphere product for loading the indissoluble medicament. The grain size of the product prepared from the method is uniform. The preparation method is applicable to medicaments which are insoluble in water but soluble in fat, and can be used for controlling nanocrystallines of the indissoluble medicament to be uniformly distributed in the nanosphere in an in-situ crystallization way so as to improve the medicament loading efficiency.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, relates to the application of nanocarriers in the field of biotechnology, in particular to a chitosan-chitosan derivative nanosphere loaded with insoluble drugs, a preparation method and its application as an oral preparation. Chitosan nanospheres loaded with insoluble drugs reach the lesion site after oral administration and exert the drug effect. The invention has potential clinical therapeutic application value. Background technique [0002] Poorly soluble drugs are water-insoluble drugs or fat-soluble drugs. In the past 10 years, researchers have used drug high-throughput screening technology to screen out a large number of active compounds used in the treatment of major diseases, but most of the screened active compounds have high molecular weight and strong hydrophobicity. At present, at least 40% of the newly developed active drugs cannot be used clinically due to the problem o...

AI Technical Summary

Problems solved by technology

However, at present, chitosan nanospheres are mainly used for loading hydrophilic drugs, and there are still many technical difficulties for loading insoluble drugs.

[0007] At present, there are difficulties in embedding insoluble drugs in hydrophilic chitosan and its derivatives: (1) hydrophilic chitosan nanospheres cannot directly load insoluble drugs. The present invention adopts O / W / O The double emulsion method realizes the loading of poorly soluble drugs, and the double emulsion can be further solidified to prepare nanospheres loaded with poorly soluble drugs

The stability of complex emulsions, especially nano-complex emulsion droplets, is a great challenge during the preparation process.

(2) Insoluble drugs such as paclitaxel are easy to crystallize to form large crystal particles during the preparation process and destroy the emulsion, resulting in drug leakage or even embedding failure

(3) Pure chitosan nanospheres have a solid structure, and it is difficult for the release liquid to enter the nanospheres, resulting in a slow drug release rate

(4) Most of the nanospheres prepared by chitosan adopt the chemical crosslinking method. After chemical crosslinking and curing, most of the active group amino groups on the surface of the nanospheres are utilized, which will greatly reduce the bioadhesion of the nanocarriers, thereby reducing the its bioavailability after administration

(5) The preparation method is very limited, mainly using mechanical stirring method, homogeneous emulsification method, ultrasonic emulsification method, etc. When using this method to prepare emulsion, due to the uneven particle size, small emulsion droplets will be absorbed by large emulsion droplets , at the same time, the large emulsion droplets will be destroyed by the shear force, which leads to the inhomogeneous particle size of the prepared chitosan nanospheres

At the same time, in the process of merging and breaking up of droplets, the internal drug can easily escape to the outside of the droplet, resulting in a decrease in the embedding rate of the drug.

The inhomogeneous particle size of nanospheres will also bring many difficulties to the practical application of chitosan and its derivative nanospheres.

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