Cyclodextrin is a water-soluble, non-reducing, white crystal that is not easily hydrolyzed by acid, non-toxic, edible, and porous. The "hydrophobic inside, hydrophilic outside" molecular structure of betacyclodextrin gives it many chemical properties and uses. A wide range of guests can form inclusion complexes with cyclodextrins, such as organic molecules, inorganic ions, biological small molecules, complexes, polymers and even inert gases. Guest molecules whose molecular size is suitable for their cave size, as long as the polarity is less than water, may substitute small molecules and enter the cyclodextrin cavity to form clathrates. The research of cyclodextrin in China began in the late 1970s, and has developed to the industrial production of betacyclodextrin.
Conditions for the formation of inclusion compounds
The ability to form clathrates is one of the most important properties of cyclodextrins, in which the encapsulated compound molecule is often referred to as the "guest" and the cyclodextrin molecule is referred to as the "subject". The formation of cyclodextrin inclusion compounds is affected by internal factors and external conditions. The intrinsic factors depend on the basic properties of cyclodextrins and their object. It can be summarized into the following three aspects: hydrophobic lipophilic interaction between host and object; Subject and object conform to spatial matching effect; Bond with the release of high-energy water. The above three factors not only affect the formation of cyclodextrin inclusions, but also directly affect the stability of the formation. The stability of the inclusion compound also depends on the properties of guest molecular groups, cavity size, molecular size and spatial configuration. a 'genes βuvari-βarcza discussed the effect of guest properties and betacyclodextrin substitution degree on the formation of inclusion compounds. It is considered that the stability of the inclusion complex depends on the spatial matching of the guest molecules, that is, the size and shape of the guest. In addition, the formation of clathrate is also affected by reaction time, reaction temperature stirring (or ultrasonic shock) time, reactant concentration and other external conditions.
Preparation method of inclusion compound
There are many preparation methods for inclusion compounds, and the suitable preparation method should be selected according to the properties of host and guest molecules and the feeding ratio in practical research and application. The guest molecule drug was added to the saturated solution of beta cyclodextrin by ultrasonic method, and immediately after mixing, the appropriate strength was selected by ultrasonic crusher or ultrasonic cleaning machine, and the appropriate time of ultrasonic shock treatment was used to replace the stirring force, and the precipitates were treated as inclusion compounds by saturated solution method. Saturated solution method
Saturated solution method is also weighed crystallization method, the betacyclodextrin is first made into saturated aqueous solution, adding the guest molecule drug, for water-insoluble drugs, it can be dissolved in appropriate organic solvent, and then injected into the betacyclodextrin saturated aqueous solution, stirring until it becomes an inclusion compound. The clathrate is precipitated by an appropriate method, and then the obtained solid clathrate can be filtered, washed and dried. By coupling the extraction process of volatile oil with the betacyclodextrin inclusion process, two new inclusion processes were formed: liquid-liquid inclusion process and gas-liquid inclusion process, which simplified the process and improved the preparation efficiency.
Grinding method
For example, in the preparation of betacyclodextrin of cinnamon oil, the betacyclodextrin is finely ground with distilled water, mixed with cinnamon oil or ethanol solution of cinnamon oil, placed in a colloid mill, fully ground until paste, filtered and dried by cold air.
Slurry process
That is, cyclodextrins and guest molecules do not need to be dissolved, but are suspended in a small amount of water at room temperature by vigorously stirring them. If ultrasound is used, the dispersion kneading method can promote the solid phase. This method is characterized by the need for less water than the slurry method. Cyclodextrin is kneaded with a small amount of water and then the calculated ratio of guest molecules is added directly, without the need for any solvent.
Freeze-drying process
Cyclodextrin inclusions that are easily soluble in water, not easy to precipitate, or inclusions that are easily decomposed and discolored when heated and dried can be dried by freeze-drying method. Freeze-drying method makes the inclusion compound loose in shape and good in solubility, and can be made into powder injection. Spray drying
If the prepared inclusion compound is easily soluble in water and stable in heat, it can be prepared by spray drying method with short drying temperature and high heating time and high yield.
Identification of inclusion compounds
The study of cyclodextrin inclusion compounds is often carried out in both solid and liquid states. There are many methods for the detection of solid clathrates, such as X-ray diffraction, differential thermal analysis, layer chromatography infrared spectroscopy and nuclear magnetic resonance.
