CN113416266A - Aromatic hydrazide compound-cyclodextrin inclusion compound and preparation method thereof - Google Patents

Aromatic hydrazide compound-cyclodextrin inclusion compound and preparation method thereof Download PDF

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CN113416266A
CN113416266A CN202110697408.9A CN202110697408A CN113416266A CN 113416266 A CN113416266 A CN 113416266A CN 202110697408 A CN202110697408 A CN 202110697408A CN 113416266 A CN113416266 A CN 113416266A
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cyclodextrin
hydrazide
compound
aromatic
hydrazine
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王龙胜
羊智成
黄莹莹
郭超
吴子杭
董宇嘉
徐梓康
熊锐
艾树轩
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Hubei University of Technology
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Abstract

Disclosure of the inventionAn aroyl hydrazide compound and cyclodextrin inclusion compound and a preparation method thereof are provided. The aromatic hydrazide compound and cyclodextrin inclusion compound is an inclusion compound obtained by supermolecular assembly of aromatic hydrazide compound and Cyclodextrin (CD), and the molecular structure of the inclusion compound is
Figure DDA0003129063270000011
Wherein M is aromatic heterocycle or substituted aryl, and CD is cyclodextrin. The preparation method comprises the following steps: (1) weighing aromatic hydrazide compounds and cyclodextrin, adding into secondary distilled water, heating, stirring and dissolving to obtain colorless solution; (2) carrying out heat preservation reaction on the colorless solution until the reaction is complete; (3) and (3) concentrating the solution obtained in the step (2), and removing the solvent to obtain the inclusion compound of the aromatic hydrazide compound and the cyclodextrin. The clathrate compound prepared by the invention has good biocompatibility and low cost. The preparation method is simple, the raw materials are easy to obtain, the production conditions are easy to control, the yield is high, and the method can be used for large-scale production.

Description

Aromatic hydrazide compound-cyclodextrin inclusion compound and preparation method thereof
Technical Field
The invention belongs to the technical field of inclusion compounds, and particularly relates to an aromatic hydrazide compound-cyclodextrin inclusion compound and a preparation method thereof.
Background
Aroylheteroazides are a class of biologically active organic molecules. Such as isoniazid, namely ramification, has excellent pharmaceutical activity for inhibiting tubercle bacillus, and is still a main drug for treating tuberculosis until now; isoxazole hydrazide, i.e. isocarboxazid, smoothie, is an antidepressant; recent studies have shown that hydrazide ligands such as m-phenoxybenzoyl hydrazine, p-phenoxybenzoyl hydrazine, nicotinyl hydrazide and the like have good anti-leishmania activity. The development of drug molecules into different dosage forms is a key technical link in drug research and development and pesticide application.
An Inclusion compound (supramolecular compound) is a supramolecular compound formed by molecules encapsulated in cavities of another molecule. The inclusion compound consists of two parts of Host molecules and guest molecules, and outer-layer molecules with cavities for inclusion are called Host molecules (Host molecules); the molecule that is included in the cavity of the host molecule is called a Guest molecule (Guest molecule).
As a second generation supramolecular host, cyclodextrins have very wide applications in the fields of medicine, food, supramolecular chemistry, and the like. Cyclodextrin (CD for short) is a general name of a class of cyclic oligosaccharides formed by amylose under specific enzyme catalysis, and generally contains 6-12D-glucopyranose units. The cyclodextrin molecules containing 6, 7 and 8 glucose units are more researched and are respectively called alpha-, beta-and gamma-cyclodextrin. The cyclodextrin molecule has a tapered barrel-like structure with the outside of the cavity being hydrophilic and the inside of the cavity being hydrophobic. The sizes of the inner cavities of the cyclodextrin inclusion compounds are respectively that the solubility, the stability and the optical properties of the cyclodextrin inclusion compounds are changed to a certain extent due to the unique structure of cyclodextrin.
The Cyclodextrin (CD) inclusion technique is a new technique which is currently applied to the field of pharmaceutical preparations. The cyclodextrin is included with oily substance to obtain solid powder with slow release effect, so as to reduce oil volatilization, and increase solubility of corresponding compound. The inclusion compound formed by the cyclodextrin can be prepared into different dosage forms such as tablets, capsules, emulsions and the like, and has wide application prospect.
At present, no report of inclusion compound of aromatic hydrazide compound and cyclodextrin is found.
Disclosure of Invention
In order to solve the technical problems, the invention provides the aromatic hydrazide compound-cyclodextrin inclusion compound and the preparation method thereof, and can provide a new inclusion compound dosage form for the application of the aromatic hydrazide compound.
The technical scheme provided by the invention is as follows:
in a first aspect, the invention provides an aromatic hydrazide compound-cyclodextrin inclusion compound which is obtained by supermolecular assembly of an aromatic hydrazide compound and cyclodextrinThe molecular structure of which is
Figure BDA00031290632500000213
Wherein M is aromatic heterocycle or substituted aryl, and CD is cyclodextrin.
Further, the aroylheterohydrazide is selected from nicotinyl hydrazide, isoniazid, furan hydrazide, thiophene hydrazide or pyrazine hydrazide; the substituted aryl hydrazide is selected from p-hydroxybenzoyl hydrazine, p-bromobenzoyl hydrazine, p-iodobenzoyl hydrazine, m-iodobenzoyl hydrazine, o-iodobenzoyl hydrazine and 3, 4-diiodobenzoyl hydrazine.
Further, the cyclodextrin is selected from alpha-cyclodextrin, beta-cyclodextrin, hydroxypropyl beta-cyclodextrin or gamma-cyclodextrin.
Preferably, if the aroyl hydrazide compound is substituted aryl hydrazide, beta-cyclodextrin is selected as the cyclodextrin, and the aroyl hydrazide is included by using the beta-cyclodextrin, so that the problem of low solubility of the aroyl hydrazide in water can be solved, and the slow release of the aroyl hydrazide can be realized.
The invention provides an inclusion compound of aroylheterohydrazide and Cyclodextrin (CD), which comprises the following components in part by weight:
Figure BDA0003129063250000021
Figure BDA00031290632500000214
Figure BDA0003129063250000022
Figure BDA0003129063250000023
Figure BDA0003129063250000024
Figure BDA0003129063250000025
Figure BDA0003129063250000026
inclusion complexes of substituted aryl hydrazides with Cyclodextrins (CD) include:
Figure BDA0003129063250000027
Figure BDA0003129063250000028
Figure BDA0003129063250000029
Figure BDA00031290632500000210
Figure BDA00031290632500000211
Figure BDA00031290632500000212
the clathrate compound is obtained by supermolecule assembly. The cyclodextrin is a cyclic molecule with a cavity formed by glucose cyclopolymerization, has the characteristics of internal hydrophobicity and external hydrophilicity, can include organic molecules with the same size to form a supramolecular inclusion compound, can improve the solubility of organic matters on one hand, and can realize the slow release of the organic matters on the other hand.
Further, the molar ratio of the heterocyclic hydrazide to the cyclodextrin in the inclusion compound is 1: 1.
In a second aspect, the present invention provides a method for preparing the clathrate compound of the first aspect, comprising the steps of:
(1) weighing aromatic hydrazide compounds and cyclodextrin, adding into secondary distilled water, heating, stirring and dissolving to obtain colorless solution;
(2) carrying out heat preservation reaction on the colorless solution until the reaction is complete;
(3) and (3) concentrating the solution obtained in the step (2), and removing the solvent to obtain the inclusion compound of the aromatic hydrazide compound and the cyclodextrin.
Further, the molar ratio of the aromatic hydrazide compound to the cyclodextrin in the step (1) is 1: 1.
Further, the amount of the secondary distilled water in the step (1) is 1000 times equivalent of that of the aroylhydrazine and the cyclodextrin for neutralization.
Further, in the step (1), the reaction temperature is 50-60 ℃.
Further, in the step (2), the temperature of the heat-preservation object is 50-60 ℃; if M is aromatic heterocycle, reacting under ultrasonic for 4 minutes; and if M is the substituted aryl hydrazide, stirring and reacting under the condition of heat preservation.
Further, in the step (3), if M is an aromatic heterocycle, freeze-drying to remove the solvent, wherein the freeze-drying temperature is-20 ℃; and if M is substituted aryl hydrazide, volatilizing to remove the solvent.
The invention has the following beneficial effects:
(1) the invention uses cyclodextrin to carry out inclusion on aroyl hydrazine compounds, solves the problem of higher solubility of isoniazide in water, and because isoniazide has better water solubility, the half-life period in a human body is too short, the isoniazide is not beneficial to exerting the drug effect, so that the development of various slow release formulations of isoniazide is a trend of the current isoniazide drugs, but no report of inclusion formulations of isoniazide and cyclodextrin exists at present; meanwhile, the solubility of other aromatic hydrazide compounds is improved;
(2) the beta-cyclodextrin is used for clathrating the substituted aroylhydrazide, so that the problem of low solubility of the aroylhydrazide in water is solved, and the slow release of the aroylhydrazide can be realized;
(3) the inclusion compound has the advantages of good biocompatibility and low cost;
(4) the method for preparing the inclusion compound has the advantages of simple and convenient synthesis route, simple equipment, easily obtained raw materials, easily controlled production conditions and high yield, and can be used for industrial production;
(5) the clathrate compound prepared by the invention can be used for developing and researching drug sustained-release formulations on one hand and can also be used for developing pesticide sustained-release formulations on the other hand.
Drawings
FIG. 1 is a schematic diagram of the formation of an inclusion complex of an aroylhydrazide and a cyclodextrin;
FIG. 2 is an infrared spectrum of an isoniazid and beta-cyclodextrin inclusion compound;
FIG. 3 is an infrared spectrum of an isoniazid and alpha-cyclodextrin inclusion compound;
FIG. 4 is an infrared spectrum of thiophene and beta-cyclodextrin;
FIG. 5 is an infrared spectrum of isonicotinyl hydrazide and hydroxypropyl-beta-cyclodextrin inclusion compound;
FIG. 6 is a schematic diagram of the formation of an aroylhydrazide and a beta-cyclodextrin inclusion compound;
FIG. 7 is an infrared spectrum of a complex of m-iodobenzoyl hydrazine and beta-cyclodextrin;
FIG. 8 is an infrared spectrum of a p-iodobenzoyl hydrazine and beta-cyclodextrin inclusion compound;
FIG. 9 is an infrared spectrum of p-hydroxybenzoyl hydrazine and beta-cyclodextrin inclusion compound.
Detailed Description
The present invention will be described in more detail and fully with reference to the following examples, which are not intended to limit the scope of the invention.
The invention provides a preparation method of an aromatic hydrazide compound-cyclodextrin inclusion compound, which has certain differences based on different reactants and is respectively explained below.
1. The hydrazide compound is aroylhydrazide, and the preparation method is as follows (shown in figure 1):
(1) weighing 1 equivalent of cyclodextrin in a beaker, adding 1000 equivalents of secondary distilled water, heating to 50 ℃ under the condition of stirring, and preparing into a saturated aqueous solution of cyclodextrin for later use;
(2) weighing a proper amount of aroylheterohydrazide, dissolving in a proper amount of deionized water at 50 ℃, mixing a saturated aqueous solution of cyclodextrin with a solution of the hydrazide, performing ultrasonic treatment for 40 minutes at 50 ℃, performing rotary evaporation and concentration on the obtained solution, and freeze-drying the obtained concentrated solution to obtain an amorphous sample of the inclusion compound.
2. The hydrazide compound is substituted aryl hydrazide, and the preparation method is as follows (shown in figure 6):
(1) weighing 1 equivalent of substituted aryl hydrazide and beta-cyclodextrin according to a molar ratio, adding 1000 equivalents of secondary distilled water, adding a small amount of ethanol for assisting dissolution of the hydrazide which is insoluble in water, heating and stirring at 60 ℃ for dissolving to obtain a colorless solution;
(2) stirring the obtained solution at 60 ℃ for 16 hours, carrying out rotary evaporation and concentration on the obtained solution, placing the concentrated solution in a beaker, sealing the beaker by using a preservative film, volatilizing the solution in the air, and obtaining a large amount of colorless blocky crystals after one week.
Example 1
Weighing 0.0685g of isoniazid, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.5680g of beta-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 50 ℃ to dissolve the isoniazid, mixing the isoniazid and the beta-cyclodextrin, ultrasonically shaking for 40 minutes at 50 ℃, carrying out rotary evaporation and concentration until a small amount of precipitate appears, and freeze-drying the rest solution at-20 ℃ to obtain a large amount of white solid powder. Weight 0.6150g, yield 96.6%.
FT-IR(KBr pellet,cm-1):3354(br),2922(s),1652(s),1541(m),1418(m),1368(m),1338(m),1157(s),1080(s),1029(vs),938(m),861(m),756(s),707(m),608(m),578(s),529(m).
Example 2
0.0687g of isoniazid is weighed and heated and dissolved in 5.0ml of secondary distilled water, 0.4860g of alpha-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water and heated to 50 ℃ to be dissolved, the two are mixed, ultrasonic vibration is carried out for 40 minutes at 50 ℃, rotary evaporation and concentration are carried out until a small amount of precipitate appears, and the rest solution is frozen and dried at-20 ℃ to obtain a large amount of white solid powder. Weight 0.5230g, yield 94.5%.
FT-IR(KBr pellet,cm-1):3337(br),2927(s),1654(s),1541(s),1412(m),1364(m),1331(s),1153(s),1079(s),1031(vs),950(s),846(m),757(s),703(m),574(s).
Example 3
Weighing 0.0683g of isoniazid benzoyl hydrazine, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.6485g of gamma-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 50 ℃ to dissolve, mixing the two, ultrasonically shaking at 50 ℃ for 40 minutes, carrying out rotary evaporation and concentration until a small amount of precipitate appears, and freeze-drying the rest solution at-20 ℃ to obtain a large amount of white solid powder. Weight 0.6980g, yield 97.3%.
FT-IR(KBr pellet cm-1):3072(w),1632(m),1597(m),1479(m),1433(s),1415(m),1384(w),1229(w),1161(w),1110(w),1095(m),1057(w),1045(w),1028(w),848(m),750(s),696(s),545(m),522(s),504(m),489(m).
Example 4
Weighing 0.0685g of isoniazid, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.7710g of 2-HP-beta-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 50 ℃ to dissolve, mixing the two, ultrasonically shaking at 50 ℃ for 40 minutes, carrying out rotary evaporation and concentration until a small amount of precipitate appears, and freeze-drying the rest solution at-20 ℃ to obtain a large amount of white solid powder. Weight 0.8011g, yield 95.6%.
FT-IR(KBr pellet,cm-1):3385(br),2928(s),1654(s),1555(s),1457(m),1413(m),1335(m),1156(s),1082(s),1033(vs),948(s),849(m),756(s),707(m),683(m),583(m).
Example 5
Weighing 0.0685g of nicotinhydrazide, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.5677g of beta-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 50 ℃ to dissolve the beta-cyclodextrin, mixing the beta-cyclodextrin and the secondary distilled water, ultrasonically shaking at 50 ℃ for 40 minutes, carrying out rotary evaporation and concentration until a small amount of precipitate appears, and freeze-drying the rest solution at-20 ℃ to obtain a large amount of white solid powder. Weight 0.6120g, yield 96.2%.
FT-IR(KBr pellet,cm-1):3082(w),1632(m),1597(m),1480(m),1432(m),1415(m),1384(w),1226(w),1158(w),1094(m),1027(w),848(m),750(m),649(s),570(w),521(s),509(w),487(w).
Example 6
Weighing 0.0630g of furan-2-hydrazide, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.5682g of beta-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 50 ℃ to dissolve, mixing the two, ultrasonically shaking at 50 ℃ for 40 minutes, carrying out rotary evaporation and concentration until a small amount of precipitate appears, and freeze-drying the rest solution at-20 ℃ to obtain a large amount of white solid powder. Weight 0.6028g, yield 95.5%.
FT-IR(KBr pellet,cm-1):3365(w),2926(m),2360(s),2342(s),1653(m),1594(m),1559(m),1418(m),1363(m),1157(s),1080(s),1029(vs),947(m),755(s),705(m),579(s),529(m).
Example 7
0.0710g of thiophene-2-hydrazide is weighed and heated and dissolved in 5.0ml of secondary distilled water, 0.5683g of beta-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water and heated to 50 ℃ to be dissolved, the two are mixed, ultrasonic vibration is carried out for 40 minutes at 50 ℃, rotary evaporation and concentration are carried out until a small amount of precipitate appears, and the rest solution is frozen and dried at-20 ℃ to obtain a large amount of white solid powder. Weight 0.6052g, yield 94.6%.
FT-IR(KBr pellet,cm-1):3355(w),2924(s),2359(s),1635(m),1418(m),1384(w),1157(s),1080(s),1029(vs),947(m),862(w),755(m),707(m),609(m),579(s),529(s).
Example 8
Weighing 0.0673g of p-hydroxybenzoyl hydrazine, heating and dissolving in 5.0ml of secondary distilled water, weighing 0.5677g of beta-cyclodextrin, dissolving in 10.0ml of secondary distilled water, heating to 60 ℃ to dissolve the beta-cyclodextrin, mixing the beta-cyclodextrin and the secondary distilled water, stirring for 16 hours at 60 ℃, performing rotary evaporation and concentration, filtering the rest solution, putting the filtered solution into a beaker, covering and punching a plurality of small holes with a preservative film, precipitating a large amount of colorless crystals after one week, weighing 0.5210g and obtaining the yield of 82%. FT-IR (KBr pellet, cm)-1):3071(w),2925(w),1631(m),1596(m),1569(m),1478(m),1433(s),1416(m),1384(m),1230(w),1182(w),1094(m),1027(w),848(m),835(m),745(m),695(s),574(m),522(s),504(m),491(m).
Example 9
Weighing 0.1075g of p-bromobenzoyl hydrazine, heating and dissolving in a mixed solvent of 10.0ml of secondary distilled water and 2.0ml of absolute ethanol, and weighing beta-0.5673g of cyclodextrin is dissolved in 10.0ml of secondary distilled water, the mixture is stirred for 16 hours at the temperature of 60 ℃, the mixture is concentrated by rotary evaporation, the residual solution is filtered and put into a beaker, a plurality of small holes are punched by a preservative film, a large amount of colorless crystals are separated out after one week, the weight is 0.5737g, and the yield is 85 percent. FT-IR (KBr pellet, cm)-1):3310(br),2922(s),1663(m),1617(s),1559(s),1338(m),1157(s),1080(s),1028(vs),945(s),835(m),753(s),704(m),579(s),528(m).
Example 10
0.1312g of p-iodobenzoyl hydrazine is weighed, heated and dissolved in a mixed solvent of 10.0ml of secondary distilled water and 2.0ml of absolute ethyl alcohol, 0.5679g of beta-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water at the temperature of 60 ℃, stirred for 16 hours, evaporated and concentrated in a rotary manner, the rest solution is filtered and put into a beaker, a plurality of small holes are punched by a preservative film, a large amount of colorless crystals are separated after one week, the weight is 0.5453g, and the yield is 78%. FT-IR (KBr pellet cm)-1):3072(w),1632(m),1597(m),1479(m),1433(s),1415(m),1384(w),1229(w),1161(w),1110(w),1095(m),1057(w),1045(w),1028(w),848(m),750(s),696(s),545(m),522(s),504(m),489(m).
Example 11
0.1310g of m-iodobenzoyl hydrazine is weighed, heated and dissolved in a mixed solvent of 10.0ml of secondary distilled water and 2.0ml of absolute ethyl alcohol, 0.5671g of beta-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water at the temperature of 60 ℃, stirred for 16 hours, evaporated and concentrated in a rotary manner, the rest solution is filtered and put into a beaker, a plurality of small holes are punched by a preservative film, a large amount of colorless crystals are separated after one week, the weight is 0.5585g, and the yield is 80%. FT-IR (KBr pellet, cm)-1):3363(br),2922(s),1654(s),1417(m),1368(m),1157(s),1080(s),1029(vs),938(s),860(s),756(m),707(s),609(m),578(s),531(m).
Example 12
0.1314g of o-iodobenzoyl hydrazine is weighed, heated and dissolved in a mixed solvent of 10.0ml of secondary distilled water and 2.0ml of absolute ethyl alcohol, 0.5668g of beta-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water at 60 ℃, stirred for 16 hours, evaporated and concentrated in a rotary manner, the rest solution is filtered and put into a beaker, a plurality of small holes are punched by a preservative film, a large amount of colorless crystals are separated out after one week, the weight is 0.5237g, and the yield is 75 percent.Found(％):C 50.25,H 3.42,N 5.08.FT-IR(KBr pellet,cm-1):3082(w),1632(m),1597(m),1480(m),1432(m),1415(m),1384(w),1226(w),1158(w),1094(m),1027(w),848(m),750(m),649(s),570(w),521(s),509(w),487(w).
Example 13
0.0970g of 3, 4-diiodobenzoyl hydrazine is weighed and heated and dissolved in a mixed solvent of 10.0ml of secondary distilled water and 4.0ml of absolute ethyl alcohol, 0.2836g of beta-cyclodextrin is weighed and dissolved in 10.0ml of secondary distilled water, the mixture is stirred for 16 hours at the temperature of 60 ℃, rotary evaporation and concentration are carried out, the rest solution is filtered and put into a beaker, a plurality of small holes are punched by a preservative film, a large amount of colorless crystals are separated out after one week, the weight is 0.3273g, and the yield is 86%. FT-IR (KBr pellet, cm)-1):3331(br),2923(w),1717(s),1661(m),1539(m),1446(m),1368(m),1336(w),1280(s),1247(m),1157(s),1108(w),1078(s),1028(vs),945(s),757(s),703(s),650(m),606(w),574(m),527(m).
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any modification, equivalent replacement, and improvement made by those skilled in the art within the technical scope of the present invention should be included in the scope of the present invention.

Claims (10)

1. The aromatic hydrazide compound-cyclodextrin inclusion compound is characterized by being obtained by supermolecular assembly of aromatic hydrazide compound and cyclodextrin, and the molecular structure of the aromatic hydrazide compound-cyclodextrin inclusion compound is
Figure FDA0003129063240000011
Wherein M is aromatic heterocycle or substituted aryl, and CD is cyclodextrin.
2. The clathrate of claim 1, wherein: the aroylhydrazine is selected from nicotinyl hydrazide, isoniazid, furan hydrazide, thiophene hydrazide or pyrazine hydrazide; the substituted aryl hydrazide is selected from p-hydroxybenzoyl hydrazine, p-bromobenzoyl hydrazine, p-iodobenzoyl hydrazine, m-iodobenzoyl hydrazine, o-iodobenzoyl hydrazine or 3, 4-diiodobenzoyl hydrazine.
3. The clathrate of claim 1, wherein: the cyclodextrin is selected from alpha-cyclodextrin, beta-cyclodextrin, hydroxypropyl beta-cyclodextrin or gamma-cyclodextrin.
4. The clathrate of claim 1, wherein: the molar ratio of the aromatic hydrazide compound to the cyclodextrin in the inclusion compound is 1: 1.
5. A method for preparing a clathrate compound described in any one of claims 1 to 4, characterized by comprising the steps of:
(1) weighing aromatic hydrazide compounds and cyclodextrin, adding into secondary distilled water, heating, stirring and dissolving to obtain colorless solution;
(2) carrying out heat preservation reaction on the colorless solution until the reaction is complete;
(3) and (3) concentrating the solution obtained in the step (2), and removing the solvent to obtain the inclusion compound of the aromatic hydrazide compound and the cyclodextrin.
6. The method of claim 5, wherein: in the step (1), the molar ratio of the aromatic hydrazide compound to the cyclodextrin is 1: 1.
7. The method of claim 5, wherein: the using amount of the secondary distilled water in the step (1) is 1000 times equivalent of the sum of the aroylhydrazide and the cyclodextrin.
8. The method of claim 5, wherein: in the step (1), the reaction temperature is 50-60 ℃.
9. The method of claim 5, wherein: in the step (2), the temperature of the heat-preservation object is 50-60 ℃; if M is aromatic heterocycle, reacting under ultrasonic for 60 minutes; and if M is the substituted aryl hydrazide, stirring and reacting under the condition of heat preservation.
10. The method of claim 5, wherein: in the step (3), if M is an aromatic heterocycle, freeze-drying to remove the solvent, wherein the freeze-drying temperature is-20 ℃; and if M is substituted aryl hydrazide, volatilizing to remove the solvent.
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