An iodine-loaded nano-composite gel drug sustained-release preparation, its preparation method and application

Abstract

The present invention belongs to the technical field of medical polymer materials, and particularly relates to an iodine-loaded nano-composite gel drug sustained-release preparation, its preparation method and application. The iodine-loaded nano-composite gel drug sustained-release preparation disclosed by the present invention comprises 5-45 wt% of a nano-composite gel carrier material, 0.01-5 wt% of iodine, and the balance of a solvent. The nano-composite gel carrier material comprises 5-95 wt% of an amphiphilic block copolymer and 95-5 wt% of saponite. A thermosensitive hydrogel is formed by the interaction between saponite and the amphiphilic block copolymer, and further iodine is encapsulated into the gel to obtain an injectable or sprayable nano-composite gel preparation loaded with iodine; based on the complexation interaction between iodine and the hydrophilic block in the amphiphilic block copolymer, the slow release of the drug in the gel carrier is realized, and the antibacterial action time is prolonged. At the same time, the presence of saponite effectively promotes blood coagulation. The iodine-loaded nano-composite gel drug sustained-release preparation disclosed by the present invention can be used for wound repair and long-term antibacterial.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical polymer materials, and particularly relates to an iodine-loaded nano-composite gel drug sustained-release preparation, a preparation method thereof, and an application thereof. Background Art

[0002] Bacterial infection refers to a disease in which pathogenic bacteria invade the blood from a wound or internal infection, disrupting the balance of the human internal environment and causing local or even systemic inflammatory responses in the human body. Iodophor is an extremely typical antibacterial agent, which is a complex formed by iodine and surfactants such as polyvinylpyrrolidone PVP. It can effectively inhibit or even eliminate the growth of pathogenic microorganisms such as bacteria by utilizing the oxidative bactericidal properties of iodine and its derivatives such as hypoiodous acid. Therefore, for the treatment of indications related to bacterial infection such as wound repair, iodophor is a very effective treatment means. However, since iodophor is always a substance existing in a solution state, there are problems of easy loss in vitro and easy absorption in vivo, and it can only play a short-term disinfection and sterilization effect, and it is difficult to meet the clinical requirements for long-term antibacterial.

[0003] Injectable thermosensitive hydrogels have attracted much attention in the research of long-acting sustained-release preparations due to their good biocompatibility, simple operation, and minimally invasive drug delivery. It is in a flowable solution state at low temperature, which endows the system with good injectability and can directly encapsulate active substances such as drugs through a simple physical mixing method; as the temperature rises, the system changes from a solution state to a gel state, thereby embedding the active substances into the gel interior, and under the action of active substance diffusion and / or gel self-degradation, drugs and the like can gradually be released from the gel, thereby achieving sustained release.

[0004] Therefore, finding a medical material that can effectively extend the antibacterial action time of iodophor has become an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, the first object of the present invention is to address the problem of the short antibacterial action time of iodophor. A nano-composite thermogel formed by mixing a copolymer formed with polyvinylpyrrolidone as a hydrophilic block and polyamino acid as a hydrophobic block with lithium alginate is used as a carrier material. Based on the complexation interaction between iodine and the hydrophilic block of the polymer, the slow release of the drug in the gel carrier is realized, the antibacterial action time is extended, and the regulation of the thermogel behavior and gelation temperature by lithium alginate itself, as well as its promoting effect on blood coagulation, are combined to provide an iodine-loaded nano-composite gel drug sustained-release preparation.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] An iodine-loaded nanocomposite gel drug sustained-release preparation comprises 5-45wt% of a nanocomposite gel carrier material, 0.01-5wt% of iodine and the remainder of a solvent, wherein the nanocomposite gel carrier material comprises 5-95wt% of an amphiphilic block copolymer and 95-5wt% of lithium tantalum.

[0008] Preferably, the content of the iodine element in the sustained-release drug preparation is 0.1-1 wt %, and the nanocomposite gel carrier material comprises 25-95 wt % of the amphiphilic block copolymer and 75-5 wt % of lithium terephthalate.

[0009] It is worth noting that lithium diatomite is a synthetic lithium magnesium silicate nanoparticle with an empirical chemical formula of Na + 0.7 [Mg 5.5 Li 0.3 Si8O 20 (OH)4] - 0.7 , the structure is a 2:1 crystal of two silicon-oxygen tetrahedra sandwiching a magnesium-oxygen octahedron, in the form of nanosheets with a diameter of 25nm and a thickness of 0.92nm. The surface of lithium algae has a high negative charge, and the charge on its edge is pH-dependent. It is positively charged when the pH is less than 9. This property allows it to form a gel through the electrostatic interaction of adjacent nanosheets at a certain concentration. In the product, the positive charge on the edge of the nanosheet is also shielded by adding an inorganic pyrophosphate dispersant, so that lithium algae can still flow freely at a solution concentration of up to 30%. In addition, lithium algae also has the property of being exfoliable, and the degree of exfoliation directly affects the adsorption capacity, viscoelasticity and thixotropy of the surface of the nanosheet. These properties make it widely used in the field of biomedical materials.

[0010] As a small molecule, iodine element is easily likely to have an early burst release of the drug when simply mixed into the gel, resulting in reduced bioavailability of the drug and greatly shortening the antibacterial action time. Therefore, for the main component of the thermohydrogel, the amphiphilic block copolymer, polyvinyl pyrrolidone, one of the main components of iodine tincture, was considered in the selection of its hydrophilic block, which can form a complex interaction with iodine, thereby effectively avoiding this burst release; in the selection of its hydrophobic block, polyamino acid blocks with good biocompatibility were considered; further, lithium nitrate was added to the block copolymer, and a gel preparation was obtained through the interaction between the two. By changing the composition of the block copolymer, the length and ratio of the hydrophilic and hydrophobic blocks, and the type and content of lithium nitrate, the gelation temperature and modulus of the gel preparation can be effectively adjusted. The gel preparation is used to encapsulate drug iodine, and long-term antibacterial is achieved based on the interaction between iodine and the polymer carrier. Combined with the coagulant effect of lithium nitrate, rapid healing of open wounds can be achieved, and it is expected to be used as a long-term antibacterial material for other indications.

[0011] Furthermore, the amphiphilic block copolymer comprises 10-90 wt% of a hydrophilic block of polyvinylpyrrolidone and 90-10 wt% of a hydrophobic block of polyamino acid.

[0012] Preferably, the amphiphilic block copolymer comprises 50-70 wt% of a hydrophilic block of polyvinylpyrrolidone and 50-30 wt% of a hydrophobic block of polyamino acid.

[0013] It should be noted that the hydrophilic block of polyvinylpyrrolidone is denoted as polymer block A, and the hydrophobic block of polyamino acid is denoted as polymer block B. The amphiphilic block copolymer provided by the present invention can be a triblock copolymer of ABA type or BAB type, a diblock copolymer of AB type, a graft copolymer of A-g-B or B-g-A type, and a (AB) n type multi-block copolymer, where n is an integer from 2 to 10.

[0014] Furthermore, the average molecular weight of the hydrophilic block of polyvinylpyrrolidone is 500-55000; the hydrophobic block polyamino acid monomer is N-carboxycyclic anhydride, and the structural general formula is:

[0015]

[0016] wherein, R is *H

[0017]

[0018] Furthermore, the polyamino acid includes one or more of polyglycine, polyalanine, polyphenylalanine, poly(alanine-co-phenylalanine), polyglutamic acid, polylysine, polyaspartic acid, polyleucine, polytyrosine, and polyvaline.

[0019] Furthermore, the type of lithiophorite is one or several of RD, XLG, D, RDS, XLS, XL21 or JS.

[0020] Furthermore, the solvent is pure water, buffer solution, physiological saline, tissue culture medium, cell culture medium, animal and plant body fluids or other solvent media that do not take organic solvents as the main body.

[0021] Furthermore, the iodine-loaded nano-composite gel drug sustained-release preparation provided by the present invention further comprises 0.01-15 wt% of a regulator, and the regulator can be one or more of sugar, salt, sodium carboxymethylcellulose, iodine glycerol, dimethicone, propylene glycol, carbomer, mannitol, sorbitol, surfactant, Tween 20, Tween 40, Tween 80, xylitol, oligosaccharide, chondroitin, chitin, chitosan, collagen, gelatin, protein glue, hyaluronic acid, and polyethylene glycol.

[0022] It should be noted that neither the individual amphiphilic block copolymer nor the laponite in the present invention can form a thermosensitive hydrogel. It is necessary to form a thermosensitive hydrogel through the interaction between the two, including electrostatic interaction, hydrophobic interaction, and hydrogen bonds, etc. And the required gel mechanical strength, sol-gel transition temperature, degradation rate, etc. can be obtained by adjusting the ratio and length of the hydrophilic and hydrophobic blocks of the amphiphilic block copolymer, the content of the block copolymer, and the type and content of the laponite.

[0023] It is also worth noting that the nano-composite gel sustained-release preparation disclosed in the present invention has thermosensitivity and shear thinning properties. It is in a solution state at low temperature and can transform into a gel state when the temperature rises to 4 - 37 °C, and the preferred gel transition temperature is 15 - 30 °C; at the same time, after the temperature rises and transforms into a gel state, the preparation can be transformed from a gel state to a solution state by applying a high shear strain, and it can immediately return to the gel state after removing the shear strain. Therefore, the nano-composite gel sustained-release preparation has good injectability and sprayability.

[0024] The second object of the present invention is to provide a preparation method of the iodine-loaded nano-composite gel drug sustained-release preparation as described above.

[0025] A preparation method of an iodine-loaded nano-composite gel drug sustained-release preparation, dissolving the amphiphilic block copolymer rapidly at low temperature in the solvent, adding the laponite and mixing evenly to obtain the nano-composite gel carrier material, and storing it at low temperature for standby; before use, placing the nano-composite gel carrier material dissolved in the solvent at low temperature and adding iodine and mixing evenly to obtain the gel sustained-release preparation; or,

[0026] Dissolving the laponite at low temperature in the solvent, adding the amphiphilic block copolymer and dissolving it rapidly at low temperature to obtain the nano-composite gel carrier material, and storing it at low temperature for standby; before use, placing the nano-composite gel carrier material dissolved in the solvent at low temperature and adding iodine and mixing evenly to obtain the gel sustained-release preparation; or,

[0027] Dissolving the amphiphilic block copolymer rapidly at low temperature in the solvent, adding the laponite and iodine, dissolving and mixing evenly to obtain the gel sustained-release preparation, and storing it at low temperature in the dark for standby.

[0028] It should be noted that the low temperature is a temperature not higher than the sol-gel transition temperature of the nano-composite gel carrier material.

[0029] Furthermore, the preparation method of the amphiphilic block copolymer disclosed in the present invention includes:

[0030] I. Preparation of amino-terminated polyvinylpyrrolidone: Dissolve small molecule monomers vinylpyrrolidone and mercaptoethylamine in toluene solvent. After complete dissolution, add an initiator and carry out free radical polymerization reaction for 24 h under argon atmosphere; Rotary evaporate to remove most of the toluene solvent, precipitate the product with a poor solvent, pour out the supernatant, and obtain amino-terminated polyvinylpyrrolidone after vacuum drying for 24 h and put it into the next reaction;

[0031] II. Preparation of the amphiphilic block copolymer with polyvinylpyrrolidone as the hydrophilic block and polyamino acid as the hydrophobic block as described above: Dissolve the amino-terminated polyvinylpyrrolidone and a catalyst obtained above in anhydrous dichloromethane solvent, add small molecule monomer N-carboxycyclic anhydride, and react at room temperature for 24 h; Rotary evaporate to remove most of the anhydrous dichloromethane solvent, precipitate the product with a poor solvent, pour out the supernatant, and obtain the above amphiphilic block copolymer after vacuum drying for 24 h.

[0032] Exemplarily, the initiator includes azobisisobutyronitrile, azobisisoheptonitrile, hydrogen peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, dicumyl peroxide, di-tert-butyl peroxide, benzoyl peroxide, lauroyl peroxide, tert-butyl benzoate, tert-butyl peroxypivalate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, potassium persulfate, ammonium persulfate, persulfate-sulfite, persulfate-thiosulfate, persulfate-fatty amine, persulfate-fatty diamine, hydrogen peroxide-ferrous salt, benzoyl peroxide-N,N-dimethylaniline or benzoyl peroxide-copper naphthenate.

[0033] The third object proposed by the present invention is to provide an application of the iodine-loaded nano-composite gel drug sustained-release preparation as described above in the preparation of drug delivery systems, antibacterial materials, hemostatic materials, wound repair materials, bone repair materials, embolizing agents and tissue adhesives.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] (1) The nano-composite gel drug preparation proposed by the present invention has thermosensitivity and shear thinning properties. At low temperatures, the preparation is in a freely flowing solution state, and when the temperature rises to body temperature, it will change to a gel state. And this gel state can become a solution state again under the drive of high shear strain, and once the shear strain is removed, it can immediately return to the gel state. The above properties make the drug-loading preparation process of the preparation simple and convenient, and the application and administration process convenient and fast.

[0036] (2) The nano-composite gel drug preparation proposed by the present invention can effectively avoid the potential early burst release behavior of small molecule drugs through the complexation interaction between iodine and the hydrophilic block in the amphiphilic block copolymer polyvinylpyrrolidone-polyamino acid, achieve the purpose of sustained release, and realize long-term antibacterial.

[0037] (3) The nano - composite gel drug preparation proposed by the present invention can also simply adjust the modulus and gelation temperature of the gel preparation by changing the concentration of lithothamnium or amphiphilic block copolymer, so as to adapt to different physiological environments and be applied to different indications. This is more convenient compared with the adjustment methods of other thermosensitive gels that require changing the chemical structure and composition of the polymer.

[0038] (4) The nano - composite gel drug sustained - release preparation proposed by the present invention combines the pro - coagulation effect of lithothamnium itself and the long - acting antibacterial effect of iodine in the preparation, effectively targeting the hemostasis period and inflammatory reaction period of wound healing. In the early stage, lithothamnium promotes platelet adhesion and helps with blood coagulation, and in the later stage, the long - acting release of iodine effectively inhibits bacterial infection, thus achieving the rapid healing of open wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to the provided drawings.

[0040] Figure 1 It is the MALDI - TOF spectrum of PVP - NH2 in Example 2 of the present invention.

[0041] Figure 2 It is PVP in Example 7 of the present invention 1290-DL -PA 480 of the nuclear magnetic spectrum.

[0042] Figure 3 It is PVP in Example 13 of the present invention 1290-DL -PA 480 Optical photos at different concentrations and the corresponding ultraviolet absorption curves.

[0043] Figure 4 It is the variable - temperature dynamic rheological curve of 10% amphiphilic block copolymer solution (10P0L) in Example 14 of the present invention.

[0044] Figure 5 It is the variable - temperature dynamic rheological curve of 10% amphiphilic block copolymer / 3% lithothamnium composite solution (10P3L) in Example 18 of the present invention.

[0045] Figure 6 It is the variable - temperature dynamic rheological curve of 10% amphiphilic block copolymer / 4% lithothamnium composite solution (10P4L) in Example 19 of the present invention.

[0046] Figure 7It is the variable-temperature dynamic rheological curve of the 10% amphiphilic block copolymer / 5% lithargite composite solution (10P5L) in Example 21 of the present invention.

[0047] Figure 8 It is the variable-temperature dynamic rheological curve of the 10% amphiphilic block copolymer / 8% lithargite composite solution (10P8L) in Example 23 of the present invention.

[0048] Figure 9 It is the variable-temperature dynamic rheological curve of the 8% amphiphilic block copolymer / 4% lithargite composite solution (8P4L) in Example 24 of the present invention.

[0049] Figure 10 It is the variable-temperature dynamic rheological curve of the 8% amphiphilic block copolymer / 5% lithargite composite solution (8P5L) in Example 25 of the present invention.

[0050] Figure 11 It is the shear-thinning rheological curve of the 10% amphiphilic block copolymer / 3.5% lithargite composite solution (10P3.5L) in Example 26 of the present invention. Detailed implementation manners

[0051] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0052] The special term "embodiment" here, any embodiment described as "exemplary" does not have to be interpreted as superior to or better than other embodiments. For the performance index tests in the embodiments of the present application, unless otherwise specified, the conventional test methods in the art are adopted. It should be understood that the terms described in the present application are only for describing specific embodiments and are not used to limit the content disclosed in the present application.

[0053] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as commonly understood by those of ordinary skill in the technical field to which the present application belongs; the test methods and technical means not specifically noted in the present application are the experimental methods and technical means commonly adopted by those of ordinary skill in the art.

[0054] As used herein, the terms "substantially" and "about" are used to describe minor fluctuations. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. Numerical data presented or represented herein in a range format is used only for convenience and brevity and should therefore be interpreted flexibly as including not only the values explicitly recited as the bounds of the range, but also all individual values or sub-ranges included within that range. For example, a numerical range of "1 to 5%" should be interpreted as including not only the explicitly recited values of 1% to 5%, but also the individual values and sub-ranges within the indicated range. Thus, individual values such as 2%, 3.5%, and 4% and sub-ranges such as 1% to 3%, 2% to 4%, and 3% to 5% etc. are included within this numerical range. This principle also applies to ranges that list only one numerical value. In addition, such an interpretation applies regardless of the width of the range or the characteristics described.

[0055] For a better illustration of the content of the present application, numerous specific details are given in the following specific embodiments. Those skilled in the art should understand that the present application can also be implemented without some of these specific details. In the embodiments, some methods, means, instruments, equipment, etc. well-known to those skilled in the art are not described in detail in order to highlight the gist of the present application.

[0056] On the premise of no conflict, the technical features disclosed in the embodiments of the present application can be combined arbitrarily, and the obtained technical solutions belong to the content disclosed in the embodiments of the present application.

[0057] The present invention discloses an iodine-loaded nano-composite gel drug sustained-release preparation, which comprises 5 to 45 wt% of a nano-composite gel carrier material, 0.1 to 1 wt% of iodine, and the balance of a solvent.

[0058] Preferably, the iodine-loaded nano-composite gel drug sustained-release preparation comprises 5 to 45 wt% of a nano-composite gel carrier material, 0.01 to 5 wt% of iodine, and the balance of a solvent

[0059] The nano-composite gel carrier material comprises 5 to 95 wt% of an amphiphilic block copolymer and 95 to 5 wt% of saponite. Among them, the amphiphilic block copolymer comprises 10 to 90 wt% of a hydrophilic block polyvinylpyrrolidone and 90 to 10 wt% of a hydrophobic block polyamino acid; the saponite model is one or several of RD, XLG, D, RDS, XLS, XL21 or JS.

[0060] Preferably, the nano-composite gel carrier material comprises 25 to 95 wt% of an amphiphilic block copolymer and 75 to 5 wt% of saponite.

[0061] The solvent is pure water, buffer solution, physiological saline, tissue culture medium, cell culture medium, animal and plant body fluids or other solvent media that do not have an organic solvent as the main body.

[0062] Preferably, the iodine-loaded nano-composite gel drug sustained-release preparation further comprises 0.01-15 wt% of a regulator, and the regulator can be one or more of sugar, salt, sodium carboxymethylcellulose, iodine glycerol, dimethicone, propylene glycol, carbomer, mannitol, sorbitol, surfactant, Tween 20, Tween 40, Tween 80, xylitol, oligosaccharide, chondroitin, chitin, chitosan, collagen, gelatin, protein glue, hyaluronic acid, polyethylene glycol.

[0063] The present invention also discloses a preparation method of the iodine-loaded nano-composite gel drug sustained-release preparation as described above:

[0064] Method 1: At 0-4°C, the amphiphilic block copolymer is rapidly stirred and dissolved in the solvent at a speed of 100-1000 rpm within 3 h, and the lithium alginate is added and stirred and mixed evenly at a speed of 100-1000 rpm to obtain the nano-composite gel carrier material, which is stored at low temperature below 4°C for standby; before use, iodine is added to the nano-composite gel carrier material dissolved in the solvent at 0-4°C, and stirred and mixed evenly at a speed of 100-1000 rpm to obtain the gel sustained-release preparation;

[0065] Method 2: At 0-4°C, the lithium alginate is stirred and dispersed in the solvent at a speed of 100-1000 rpm, and the amphiphilic block copolymer is added and rapidly stirred and dissolved at a speed of 100-1000 rpm within 3 h to obtain the nano-composite gel carrier material, which is stored at low temperature below 4°C for standby; before use, iodine is added to the nano-composite gel carrier material dissolved in the solvent at 0-4°C, and stirred and mixed evenly at a speed of 100-1000 rpm to obtain the gel sustained-release preparation;

[0066] Method 3: At 0-4°C, the amphiphilic block copolymer is rapidly stirred and dissolved in the solvent at a speed of 100-1000 rpm within 3 h, the lithium alginate and iodine are added, and after dissolution and mixing, the gel sustained-release preparation is obtained, which is stored in the dark at low temperature below 4°C for standby.

[0067] It should be noted that there is no obvious difference in the preparation effects of the above three preparation methods.

[0068] Among them, the preparation method of the amphiphilic block copolymer includes:

[0069] I. Preparation of Amino-Terminated Polyvinylpyrrolidone: Add small molecule monomer vinylpyrrolidone (NVP), mercaptoethylamine and toluene solvent into a 250 mL three-necked flask, and stir magnetically at 50 °C until completely dissolved; then insert an argon gas conduit below the liquid level, and bubble to remove oxygen for 15 min to remove the dissolved oxygen in the solution, with the bubbling rate controlled at one bubble per second; after deoxygenation, add an initiator to the system under an argon atmosphere, heat up to 70 °C, and carry out free radical polymerization for 24 h; after the reaction is completed, rotary evaporate to remove most of the toluene solvent, precipitate the product with a poor solvent, pour out the supernatant, and vacuum dry for 24 h to obtain amino-terminated polyvinylpyrrolidone for the next step of the reaction;

[0070] The initiators include azobisisobutyronitrile, azobisisoheptonitrile, hydrogen peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, dicumyl peroxide, di-tert-butyl peroxide, benzoyl peroxide, lauroyl peroxide, tert-butyl perbenzoate, tert-butyl peroxypivalate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, potassium persulfate, ammonium persulfate, persulfate-sulfite, persulfate-thiosulfate, persulfate-fatty amine, persulfate-fatty diamine, hydrogen peroxide-ferrous salt, benzoyl peroxide-N,N-dimethylaniline, benzoyl peroxide-copper naphthenate.

[0071] II. Preparation of the amphiphilic block copolymer with polyvinylpyrrolidone as the hydrophilic block and polyamino acid as the hydrophobic block: Add small molecule monomer N-carboxycyclic anhydride into a dry 250 mL flask with a side port, replace the gas three times, and then inject anhydrous dichloromethane (DCM) and ultra-dry N,N-dimethylformamide (DMF) solvents (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Then add the amino-terminated polyvinylpyrrolidone into another 250 mL flask, add toluene solvent and stir to dissolve, heat up to 280 °C for azeotropic dehydration, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous dichloromethane (the molar ratio of 18-Crown-6 to amino-terminated polyvinylpyrrolidone is 1:1), stir and mix evenly, and inject it into the above monomer solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, rotary evaporate to remove most of the anhydrous dichloromethane solvent, precipitate the product with a poor solvent, pour out the supernatant, and vacuum dry for 24 h to obtain the above amphiphilic block copolymer.

[0072] To better understand the present invention, the following examples are used to further specifically illustrate the present invention, but it should not be understood as a limitation of the present invention. For some non-essential improvements and adjustments made by those skilled in the art based on the above invention content, they are also considered to fall within the protection scope of the present invention.

[0073] Example 1

[0074] Preparation of hydrophilic block polyvinylpyrrolidone (PVP-NH2):

[0075] Add 0.10 mol of N-vinylpyrrolidone (NVP), 0.012 mol of 2-mercaptoethylamine, and 65 mL of toluene solvent into a 250 mL three-necked flask, and stir magnetically at 50 °C until completely dissolved; then insert the inlet of the argon gas duct below the liquid surface, and bubble to remove oxygen for 15 min to remove the dissolved oxygen in the solution, and control the bubbling rate at one bubble per second; after the deoxygenation is completed, add 0.5 g of azobisisobutyronitrile (AIBN) initiator into the system under an argon atmosphere, raise the temperature to 70 °C, and react for 24 h. After the reaction is completed, remove most of the toluene solvent by rotary evaporation, add a small amount of anhydrous dichloromethane, stir to dissolve, and dropwise add it to 10 - 20 times the volume of ice-cold diethyl ether, precipitate at -20 °C for 24 h, filter off the upper clear liquid and vacuum dry for 24 h to obtain amino-terminated polyvinylpyrrolidone (PVP-NH2), with a yield of about 75%. The number-average and weight-average molecular weights (M n , M w ) of the above polymer were measured to be 510 and 670 respectively by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF), and the polydispersity index was 1.31.

[0076] Example 2

[0077] Preparation of hydrophilic block polyvinylpyrrolidone (PVP-NH2):

[0078] Add 0.25 mol of N-vinylpyrrolidone (NVP), 0.012 mol of 2-mercaptoethylamine, and 65 mL of toluene solvent into a 250 mL three-necked flask, and stir magnetically at 50 °C until completely dissolved; then insert the inlet of the argon gas duct below the liquid surface, and bubble to remove oxygen for 15 min to remove the dissolved oxygen in the solution, and control the bubbling rate at one bubble per second; after the deoxygenation is completed, add 0.5 g of azobisisobutyronitrile (AIBN) initiator into the system under an argon atmosphere, raise the temperature to 70 °C, and react for 24 h. After the reaction is completed, remove most of the toluene solvent by rotary evaporation, add a small amount of anhydrous dichloromethane, stir to dissolve, and dropwise add it to 10 - 20 times the volume of ice-cold diethyl ether, precipitate at -20 °C for 24 h, filter off the upper clear liquid and vacuum dry for 24 h to obtain amino-terminated polyvinylpyrrolidone (PVP-NH2), with a yield of about 77%. The number-average and weight-average molecular weights (M n , M w ) of the above polymer were measured to be 1290 and 1490 respectively by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF), and the polydispersity index was 1.20, and the results are as Figure 1 shown.

[0079] Example 3

[0080] Preparation of hydrophilic block polyvinylpyrrolidone (PVP-NH2):

[0081] Add 2 mol of vinylpyrrolidone (NVP), 0.012 mol of mercaptoethylamine, and 65 mL of toluene solvent into a 250 mL three-necked flask, and stir magnetically at 50 °C until completely dissolved; then insert the inlet of the argon gas duct below the liquid level, and bubble to remove oxygen for 15 min to remove the dissolved oxygen in the solution. The bubbling rate is controlled at one bubble per second; after the deoxygenation is completed, add 0.5 g of azobisisobutyronitrile (AIBN) initiator into the system under an argon atmosphere, raise the temperature to 70 °C, and react for 24 h. After the reaction is completed, remove most of the toluene solvent by rotary evaporation, add a small amount of anhydrous dichloromethane, stir to dissolve, and dropwise add it to 10 - 20 times the volume of ice-cold diethyl ether, and precipitate at -20 °C for 24 h. Filter off the upper clear liquid and vacuum dry for 24 h to obtain amino-terminated polyvinylpyrrolidone (PVP-NH2). The yield is about 74%. The number-average and weight-average molecular weights (M n , M w ) of the above polymer are 10300 and 13200 respectively, and the molecular weight distribution coefficient is 1.28.

[0082] Example 4

[0083] Preparation of hydrophilic block polyvinylpyrrolidone (PVP-NH2):

[0084] Add 10 mol of vinylpyrrolidone (NVP), 0.012 mol of mercaptoethylamine, and 65 mL of toluene solvent into a 250 mL three-necked flask, and stir magnetically at 50 °C until completely dissolved; then insert the inlet of the argon gas duct below the liquid level, and bubble to remove oxygen for 15 min to remove the dissolved oxygen in the solution. The bubbling rate is controlled at one bubble per second; after the deoxygenation is completed, add 0.5 g of azobisisobutyronitrile (AIBN) initiator into the system under an argon atmosphere, raise the temperature to 70 °C, and react for 24 h. After the reaction is completed, remove most of the toluene solvent by rotary evaporation, add a small amount of anhydrous dichloromethane, stir to dissolve, and dropwise add it to 10 - 20 times the volume of ice-cold diethyl ether, and precipitate at -20 °C for 24 h. Filter off the upper clear liquid and vacuum dry for 24 h to obtain amino-terminated polyvinylpyrrolidone (PVP-NH2). The yield is about 72%. The number-average and weight-average molecular weights (M n , M w ) of the above polymer are 51500 and 68000 respectively, and the molecular weight distribution coefficient is 1.32.

[0085] Example 5

[0086] Preparation of amphiphilic block copolymer (PVP- L -PA):

[0087] Add 7 g of L-alanine-N-carboxylic acid anhydride (L-Ala-NCA) into a dry 250 mL three-necked flask. After displacing the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 1 into another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the L-Ala-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is gradually added dropwise to 10 - 20 times the volume of ice-cold diethyl ether, and allowed to settle at -20 °C for 24 h. The supernatant is removed by suction filtration and vacuum dried for 24 h to obtain the polyvinylpyrrolidone-polyalanine diblock copolymer (PVP- L -PA), with a yield of about 78%. Its NMR characterization is carried out, and the calculated molecular weight of the product is 510 - 520, that is, PVP 510-L -PA 520 .

[0088] Example 6

[0089] Preparation of amphiphilic block copolymer (PVP- DL -PPhe):

[0090] In a dry 250 mL three-necked flask, add 7 g of D,L-phenylalanine-N-carboxyanhydride (D,L-Phe-NCA). After displacing the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 1 to another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the D,L-Phe-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is slowly added dropwise to 10-20 times the volume of ice-cold diethyl ether, and allowed to precipitate at -20 °C for 24 h. After filtering off the upper clear liquid and drying in vacuo for 24 h, the polyvinylpyrrolidone-polyphenylalanine diblock copolymer (PVP- DL -PPhe) is obtained, with a yield of about 76%. Its NMR characterization is carried out, and the calculated molecular weight of the product is 510-530, that is, PVP 510-DL -PPhe 530 .

[0091] Example 7

[0092] Preparation of amphiphilic diblock copolymer (PVP- DL -PA):

[0093] Add 1.5 g of L-alanine-N-carboxyanhydride (L-Ala-NCA) and 1.5 g of D-alanine-N-carboxyanhydride (D-Ala-NCA) into a dry 250 mL round-bottom flask with a side neck. After purging the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 2 into another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1). Stir and mix evenly, and inject it into the D,L-Ala-NCA solution with a long needle. React at room temperature for 24 h. After the reaction is completed, rotary evaporate to remove most of the DCM solvent, and then dropwise add it to 10 - 20 times the volume of ice-cold diethyl ether, precipitate at -20 °C for 24 h, filter off the upper clear liquid and vacuum dry for 24 h to obtain polyvinylpyrrolidone-polyalanine diblock copolymer (PVP- DL -PA), with a yield of about 74%. Perform NMR characterization on it, and the results are as Figure 2 shown. The molecular weight of the product is calculated to be 1290 - 480, that is, PVP 1290-DL -PA 480 .

[0094] Example 8

[0095] Preparation of amphiphilic diblock copolymer (PVP- L -PASP):

[0096] In a dry 250 mL three-necked flask, add 3 g of L-aspartic acid 4-benzyl ester-N-carboxyanhydride (L-Asp(Obzl)-NCA). After purging the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 2 to another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the L-Ala-Asp(Obzl)-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is gradually added dropwise to 10-20 times the volume of ice-cold diethyl ether, and allowed to settle at -20 °C for 24 h. The upper clear liquid is removed by suction filtration and vacuum dried for 24 h to obtain the polyvinylpyrrolidone-polyaspartic acid diblock copolymer (PVP- L -PASP), with a yield of about 76%. Its NMR characterization was carried out, and the calculated molecular weight of the product was 1290-580, that is, PVP 1290-L -PASP 580 .

[0097] Example 9

[0098] Preparation of amphiphilic diblock copolymer (PVP- D -PPhe):

[0099] Add 3.4 g of D-phenylalanine-N-carboxyanhydride (D-Phe-NCA) into a dry 250 mL three-necked flask. After purging the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 3 into another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the D-Phe-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is gradually added dropwise to 10 - 20 times the volume of ice-cold diethyl ether, and allowed to settle at -20 °C for 24 h. After filtering off the upper clear liquid and drying in vacuo for 24 h, the polyvinylpyrrolidone-polyphenylalanine diblock copolymer (PVP- D -PPhe) is obtained, with a yield of about 78%. Its NMR characterization is carried out, and the calculated molecular weight of the product is 10300 - 5700, that is, PVP 10300-D -PPhe 5700 .

[0100] Example 10

[0101] Preparation of amphiphilic diblock copolymer (PVP- DL -PASP):

[0102] Add 1.7 g of D-Asp(Obzl)-NCA and 1.7 g of L-Asp(Obzl)-NCA into a dry 250 mL three-necked flask. After displacing the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 3 into another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the D,L-Ala-Asp(Obzl)-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is slowly added dropwise to 10-20 times the volume of ice-cold diethyl ether, and allowed to settle at -20 °C for 24 h. After filtering off the upper clear liquid and drying in vacuo for 24 h, the polyvinylpyrrolidone-polyaspartic acid diblock copolymer (PVP- DL -PASP) is obtained, with a yield of about 72%. Its NMR characterization is carried out, and the calculated molecular weight of the product is 10300 - 5670, that is, PVP 10300-DL -PASP 5670 .

[0103] Example 11

[0104] Preparation of amphiphilic diblock copolymer (PVP- L -PA):

[0105] Add 2.3 g of L-alanine-N-carboxyanhydride (L-Ala-NCA) into a dry 250 mL three-necked flask. After purging the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 4 into another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the L-Ala-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is slowly added dropwise to 10 - 20 times the volume of ice-cold diethyl ether, and allowed to precipitate at -20 °C for 24 h. Filter off the upper clear liquid and dry it under vacuum for 24 h to obtain the polyvinylpyrrolidone-polyaspartic acid diblock copolymer (PVP- L -PA), with a yield of about 72%. Perform NMR characterization on it, and calculate that the molecular weight of the product is 51500 - 22500, that is, PVP 51500-L -PA 22500 .

[0106] Example 12

[0107] Preparation of amphiphilic diblock copolymer (PVP- D -PASP):

[0108] In a dry 250 mL three-necked flask, add 2.3 g of D-aspartic acid-4-benzyl ester-N-carboxyanhydride (D-Asp(Obzl)-NCA). After purging the gas three times, inject 100 mL of anhydrous dichloromethane (DCM) and 10 mL of ultra-dry N,N-dimethylformamide (DMF) (the volume ratio of DCM to DMF is 10:1) into the system under an argon atmosphere, and stir to dissolve. Subsequently, add 5 g of the polymer PVP-NH2 obtained in Example 4 to another 250 mL eggplant-shaped flask, add 40 mL of toluene to dissolve it, raise the temperature to 280 °C for azeotropic water removal, cool to room temperature, and then add a solution of 18-crown-6 (18-Crown-6) dissolved in anhydrous DCM (the molar ratio of 18-Crown-6 to PVP-NH2 is 1:1), stir and mix evenly, and inject it into the D-Ala-Asp(Obzl)-NCA solution with a long needle, and react at room temperature for 24 h. After the reaction is completed, most of the DCM solvent is removed by rotary evaporation, and then it is slowly added dropwise to 10-20 times the volume of ice-cold diethyl ether, and allowed to precipitate at -20 °C for 24 h. After filtering off the upper clear liquid and vacuum drying for 24 h, the polyvinylpyrrolidone-polyaspartic acid diblock copolymer (PVP- D -PASP) is obtained, with a yield of about 76%. Its NMR characterization is carried out, and the calculated molecular weight of the product is 51500 - 20700, that is, PVP 51500-D -PASP 20700 .

[0109] Example 13

[0110] Dissolution property test of amphiphilic block copolymer (PVP 1290-DL -PA 480 ):

[0111] In order to investigate the dissolution property of the amphiphilic block copolymer PVP 1290-DL -PA 480 in water, a series of aqueous polymer solutions with different concentration gradients (0, 0.05, 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 10, 15 wt%) were prepared, and their absorbance at a visible light wavelength of 630 nm was measured using a UV-visible spectrophotometer. The results are as Figure 3 shown. At low concentrations, the polymer has good dissolution properties, the aqueous solution is clear and transparent and has a low absorbance. As the concentration increases, in the concentration range of 2 - 3 wt%, the solution directly changes from clear and transparent to slightly yellow and opaque, and the corresponding absorbance value will change abruptly.

[0112] Example 14

[0113] Dissolution property test of amphiphilic block copolymer (PVP 1290-DL -PA 480)Rheological property test of PBS solution:

[0114] Using phosphate buffer solution (PBS) as the solvent, the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480 was configured into a 10% 10P0L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes of the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as Figure 4 shown. The 10% PVP 1290-DL -PA 480 polymer solution has no intersection point within the test temperature range of 1 - 50 °C, cannot undergo sol-gel phase transition, and the modulus of the system at this time is only 0.56 Pa.

[0115] Example 15

[0116] Rheological property test of the pure aqueous solution of amphiphilic block copolymer (PVP 10300-D -PPhe 5700 ) :

[0117] Using pure water as the solvent, the amphiphilic block copolymer PVP in Example 9 10300-D -PPhe 5700 was configured into a 12% 12P0L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes of the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results show that the 12% PVP 10300-D -PPhe 5700 polymer solution has no intersection point within the test temperature range of 1 - 50 °C, cannot undergo sol-gel phase transition, and does not have thermosensitivity.

[0118] Example 16

[0119] Rheological property test of the saline solution of xonotlite (XLS):

[0120] Using physiological saline as the solvent, xonotlite (XLS) was respectively configured into 3%, 5%, and 8% solutions. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes of the storage modulus (G') and loss modulus (G") of each xonotlite saline solution with temperature. The results show that none of the solutions can undergo sol-gel phase transition within the test temperature range of 1 - 50 °C, and they do not have thermosensitivity.

[0121] Example 17

[0122] Preparation and Rheological Property Test of Nano-Composite Gel Carrier Material (15P3L):

[0123] At 0 - 4 °C, the amphiphilic block copolymer PVP 510-DL -PPhe 530 in Example 6 was rapidly stirred and dissolved in the solvent physiological saline containing 1 wt% of the regulator Tween-20 at a concentration of 15 wt% within 3 h, and then 3 wt% of lithothamnion (RD) was added and stirred evenly at a speed of 100 - 1000 rpm to obtain a 15P3L polymer solution. Under a fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes of the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results show that there is an intersection point between the storage modulus and the loss modulus of the 15P3L polymer solution within the test temperature range of 1 - 50 °C, indicating that it can undergo sol-gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 33 °C, and the modulus of the system at 37 °C is 15 Pa.

[0124] Example 18

[0125] Preparation and Rheological Property Test of Nano-Composite Gel Carrier Material (10P3L):

[0126] At 0 - 4 °C, the amphiphilic block copolymer PVP 1290-DL -PA 480 in Example 7 was rapidly stirred and dissolved in the solvent phosphate buffer solution (PBS) at a concentration of 10 wt% within 3 h, and then 3 wt% of lithothamnion (XLS) was added and stirred evenly at a speed of 100 - 1000 rpm to obtain a 10P3L polymer solution. Under a fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes of the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results Figure 5 show that there is an intersection point between the storage modulus and the loss modulus of the 10P3L polymer solution within the test temperature range of 1 - 50 °C, indicating that it can undergo sol-gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 30 °C, and the modulus of the system at 37 °C is 26 Pa.

[0127] Example 19

[0128] Preparation and Rheological Property Test of Nano-Composite Gel Carrier Material (10P4L):

[0129] At 0 - 4 °C, the amphiphilic block copolymer PVP in Example 7 was rapidly stirred and dissolved in the solvent phosphate buffer (PBS) at a concentration of 10 wt% within 3 h at a rotation speed of 100 - 1000 rpm. Then, 4 wt% of lithium aluminate (XLS) was added and stirred evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P4L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as 1290-DL -PA 480 shown. In the test temperature range of 1 - 50 °C, the storage modulus and loss modulus of the 10P4L polymer solution have an intersection point, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 18 °C, and the modulus of the system at 37 °C is 85 Pa. Figure 6 shown. In the test temperature range of 1 - 50 °C, the storage modulus and loss modulus of the 10P4L polymer solution have an intersection point, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 18 °C, and the modulus of the system at 37 °C is 85 Pa.

[0130] Example 20

[0131] Preparation and rheological property test of the nano - composite gel carrier material (10P4L):

[0132] At 0 - 4 °C, the amphiphilic block copolymer PVP10300 - D - PPhe5700 in Example 9 was rapidly stirred and dissolved in pure water containing 0.01 wt% of the regulator Tween - 80 at a concentration of 10 wt% within 3 h at a rotation speed of 100 - 1000 rpm. Then, 4 wt% of lithium aluminate (XL21) was added and stirred evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P4L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results show that in the test temperature range of 1 - 50 °C, the storage modulus and loss modulus of the 10P4L polymer solution have an intersection point, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 17 °C, and the modulus of the system at 37 °C is 101 Pa.

[0133] Example 21

[0134] Preparation and rheological property test of the nano - composite gel carrier material (10P5L):

[0135] At 0 - 4 °C, the amphiphilic block copolymer PVP in Example 7 was rapidly stirred and dissolved in the solvent phosphate buffer (PBS) at a concentration of 10 wt% within 3 h at a rotation speed of 100 - 1000 rpm. Then, 4 wt% of lithium aluminate (XLS) was added and stirred evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P4L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as 1290-DL -PA 480It was rapidly stirred and dissolved in the solvent phosphate buffer solution (PBS) at a concentration of 10 wt% within 3 h, and then 5 wt% of xonotlite (XLS) was added and stirred and mixed evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P5L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as Figure 7 shown. For the 10P5L polymer solution, there is an intersection point between the storage modulus and the loss modulus within the test temperature range of 1 - 50 °C, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 12 °C, and the modulus of the system at 37 °C is 195 Pa.

[0136] Example 22

[0137] Preparation and rheological property test of the nano - composite gel carrier material (4P5L):

[0138] At 0 - 4 °C, the amphiphilic block copolymer PVP 51500-D -PASP 20700 in Example 12 was rapidly stirred and dissolved in the solvent phosphate buffer solution (PBS) at a concentration of 4 wt% within 3 h, and then 5 wt% of xonotlite (XLS) was added and stirred and mixed evenly at a rotation speed of 100 - 1000 rpm to obtain a 4P5L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results show that for the 4P5L polymer solution, there is an intersection point between the storage modulus and the loss modulus within the test temperature range of 1 - 50 °C, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 9 °C, and the modulus of the system at 37 °C is 570 Pa.

[0139] Example 23

[0140] Preparation and rheological property test of the nano - composite gel carrier material (10P8L):

[0141] At 0 - 4 °C, the amphiphilic block copolymer PVP 1290-DL -PA 480Dissolve it in the solvent phosphate buffer solution (PBS) at a concentration of 10 wt% with rapid stirring within 3 h, and then add 8 wt% of xonotlite (XLS) and stir evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P8L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), use a rotational rheometer to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as Figure 8 shown. In the test temperature range of 1 - 50 °C, the storage modulus of the 10P8L polymer solution is always greater than the loss modulus, indicating that it is always in a gel state, and the modulus of the system at 37 °C is 1780 Pa.

[0142] Example 24

[0143] Preparation and rheological property test of the nano-composite gel carrier material (8P4L):

[0144] At 0 - 4 °C, rotate the amphiphilic block copolymer PVP in Example 7 at a rotation speed of 100 - 1000 rpm 1290-DL -PA 480 Dissolve it in the solvent phosphate buffer solution (PBS) at a concentration of 8 wt% with rapid stirring within 3 h, and then add 4 wt% of xonotlite (XLS) and stir evenly at a rotation speed of 100 - 1000 rpm to obtain an 8P4L polymer solution. Under fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), use a rotational rheometer to test the changes in the storage modulus (G') and loss modulus (G") of the polymer solution with temperature. The results are as Figure 9 shown. In the test temperature range of 1 - 50 °C, the storage modulus and loss modulus of the 8P4L polymer solution have an intersection point, indicating that it can undergo a sol-gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 25 °C, and the modulus of the system at 37 °C is 22 Pa.

[0145] Example 25

[0146] Preparation and rheological property test of the nano-composite gel carrier material (8P5L):

[0147] At 0 - 4 °C, rotate the amphiphilic block copolymer PVP in Example 7 at a rotation speed of 100 - 1000 rpm 1290-DL -PA 480It was rapidly stirred and dissolved in the solvent phosphate buffer solution (PBS) at a concentration of 8 wt% within 3 h, and then 5 wt% of xonotlite (XLS) was added and stirred and mixed evenly at a rotation speed of 100 - 1000 rpm to obtain an 8P5L polymer solution. Under the conditions of a fixed shear frequency (1.592 Hz), shear strain (1%), and heating rate (1 °C / min), a rotational rheometer was used to test the changes in the storage modulus (G') and loss modulus (G'') of the polymer solution with temperature. The results are as Figure 10 shown. In the test temperature range of 1 - 50 °C for the 8P5L polymer solution, there is an intersection point between the storage modulus and the loss modulus, indicating that it can undergo a sol - gel phase transition and has thermosensitivity. The phase transition temperature corresponding to the intersection point is 20 °C, and the modulus of the system at 37 °C is 48 Pa.

[0148] Example 26

[0149] Preparation and rheological property test of the nano - composite gel carrier material (10P3.5L):

[0150] At 0 - 4 °C, the amphiphilic block copolymer PVP 1290-DL -PA 480 in Example 7 was rapidly stirred and dissolved in the solvent phosphate buffer solution (PBS) at a concentration of 10 wt% within 3 h, and then 3.5 wt% of xonotlite (XLS) was added and stirred and mixed evenly at a rotation speed of 100 - 1000 rpm to obtain a 10P3.5L polymer solution. Under the conditions of a fixed test temperature (37 °C), shear frequency (1.592 Hz), and shear strain (1%), a rotational rheometer was used to test the change of the viscosity (η) of the system with the shear rate. The results are as Figure 11 shown. As the shear rate continuously increases, the viscosity of the system continuously decreases, dropping by nearly four orders of magnitude, indicating that the nano - composite hydrogel formed by the amphiphilic block copolymer and xonotlite has good shear - thinning properties.

[0151] Example 27

[0152] Rheological property test of the nano - composite gel carrier material (10P4L):

[0153] The 10P4L polymer solution obtained in Example 20 was used to test the change of the viscosity (η) of the system with the shear rate under the conditions of a fixed test temperature (37 °C), shear frequency (1.592 Hz), and shear strain (1%) using a rotational rheometer. As the shear rate continuously increases, the viscosity of the system continuously decreases, indicating that the nano - composite hydrogel formed by the amphiphilic block copolymer and xonotlite has good shear - thinning properties.

[0154] Example 28

[0155] Rheological property test of the nano-composite gel carrier material (10P4L):

[0156] The 10P4L polymer solution obtained in Example 19 was used to test the changes of the storage modulus (G') and loss modulus (G") of the system with the alternating shear strain (1% - 100% - 1% - 100% - 1% - 100%) at a fixed test temperature (37 °C) and shear frequency (1.592 Hz) using a rotational rheometer. The results showed that when the shear strain was 1%, the storage modulus (G') of the system was greater than the loss modulus (G"), and it was in the gel state; when the shear strain was 100%, the storage modulus (G') of the system was less than the loss modulus (G"), and it was in the solution state; and during the process of applying multiple alternating strains, for the same strain conditions, the modulus of the system remained almost unchanged, indicating that the nano-composite hydrogel formed by the amphiphilic block copolymer and lithium diatomite has good shear thinning properties and excellent self-healing properties at the same time.

[0157] Example 29

[0158] In vivo biocompatibility test of the nano-composite gel carrier material (10P4L):

[0159] The 10P4L polymer solution obtained in Example 19 was filtered and sterilized through a 0.2 μm sterile filter head. Approximately 0.2 mL of the above solution was injected subcutaneously into the back of an anesthetized ICR mouse. The mouse was sacrificed at specific time points, and the residual size of the nano-composite gel in the mouse body and the inflammatory conditions of the tissues around the gel were observed by dissection. The results showed that the nano-composite gel could continuously degrade in vivo for up to 60 days, and there were no conditions such as edema and tissue necrosis at the injection site of the gel, indicating that the in vivo biocompatibility of this material is acceptable.

[0160] Example 30

[0161] The 4P5L polymer solution obtained in Example 22 was filtered and sterilized through a 0.2 μm sterile filter head. Approximately 0.2 mL of the above solution was injected subcutaneously into the back of an anesthetized ICR mouse. The mouse was sacrificed at specific time points, and the residual size of the nano-composite gel in the mouse body and the inflammatory conditions of the tissues around the gel were observed by dissection. The results showed that the nano-composite gel could continuously degrade in vivo for up to 80 days, and there were no conditions such as edema and tissue necrosis at the injection site of the gel, indicating that the in vivo biocompatibility of this material is acceptable.

[0162] Example 31

[0163] Preparation test of the iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.2I:

[0164] At 0-4 °C and a rotation speed of 100-1000 rpm, the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480 was rapidly stirred and dissolved in PBS at a concentration of 10 wt% within 3 h. 4 wt% of lithium alginate (XLS) was added and stirred evenly. Further, 0.2 wt% of iodine was added at 0-4 °C. After uniform dissolution, it became an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.2I, which was stored for later use at low temperature in the dark.

[0165] Example 32

[0166] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.2I:

[0167] At 0-4 °C and a rotation speed of 100-1000 rpm, 4 wt% of lithium alginate (XLS) was stirred and dispersed in PBS. 10 wt% of the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480 was added and rapidly dissolved by stirring at a rotation speed of 100-1000 rpm within 3 h. Further, 0.2 wt% of iodine was added at 0-4 °C. After uniform dissolution, it became an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.2I, which was stored for later use at low temperature in the dark.

[0168] Example 33

[0169] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.15I:

[0170] At 0-4 °C and a rotation speed of 100-1000 rpm, the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480 was rapidly stirred and dissolved in PBS at a concentration of 10 wt% within 3 h. Further, 4 wt% of lithium alginate (XLS) and 0.15 wt% of iodine were added. After uniform dissolution, it became an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.15I, which was stored for later use at low temperature in the dark.

[0171] Example 34

[0172] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I:

[0173] At 0-4 °C and a rotation speed of 100-1000 rpm, the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480Dissolve it in PBS by rapid stirring at a concentration of 10 wt% within 3 h, add 4 wt% of lithium alginate (XLS), stir and mix evenly, further add 0.5 wt% of iodine at 0 - 4 °C. After dissolving evenly, it becomes an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I, and store it for later use at low temperature in the dark.

[0174] Example 35

[0175] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I:

[0176] Disperse 4 wt% of lithium alginate (XLS) in PBS by stirring at a speed of 100 - 1000 rpm at 0 - 4 °C, add 10 wt% of the amphiphilic block copolymer PVP 1290-DL -PA 480 in Example 7, and rapidly dissolve it by stirring within 3 h at a speed of 100 - 1000 rpm. Further add 0.5 wt% of iodine at 0 - 4 °C. After dissolving evenly, it becomes an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I, and store it for later use at low temperature in the dark.

[0177] Example 36

[0178] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I:

[0179] Dissolve the amphiphilic block copolymer PVP 1290-DL -PA 480 in Example 7 in PBS by rapid stirring at a concentration of 10 wt% within 3 h. Further add 4 wt% of lithium alginate (XLS) and 0.5 wt% of iodine. After dissolving and mixing evenly, it becomes an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I, and store it for later use at low temperature in the dark.

[0180] Example 37

[0181] Preparation test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.8I:

[0182] Dissolve the amphiphilic block copolymer PVP 1290-DL -PA 480 in Example 7 in PBS by rapid stirring at a concentration of 10 wt% within 3 h, add 4 wt% of lithium alginate (XLS), stir and mix evenly. Further add 0.8 wt% of iodine at 0 - 4 °C. After dissolving evenly, it becomes an iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.8I, and store it for later use at low temperature in the dark.

[0183] Example 38

[0184] Preparation experiment of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.8I:

[0185] At 0 - 4 °C, stir and disperse 4 wt% of lithium alginate (XLS) in PBS at a rotation speed of 100 - 1000 rpm, and add 10 wt% of the amphiphilic block copolymer PVP in Example 7 1290-DL -PA 480 , and rapidly dissolve it by stirring at a rotation speed of 100 - 1000 rpm within 3 h. Further add 0.8 wt% of iodine at 0 - 4 °C. After dissolving evenly, it becomes iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.8I, and store it for later use in low temperature and dark.

[0186] Example 39

[0187] Preparation experiment of iodine-loaded nano-composite gel drug sustained-release preparation 4P5L@2I:

[0188] At 0 - 4 °C, dissolve the amphiphilic block copolymer PVP in Example 12 51500-D -PASP 20700 at a concentration of 4 wt% in the solvent phosphate buffer (PBS) by rapid stirring within 3 h. Further add 5 wt% of lithium alginate (XLS) and 2 wt% of iodine. After dissolving and mixing evenly, it becomes iodine-loaded nano-composite gel drug sustained-release preparation 4P5L@2I, and store it for later use in low temperature and dark.

[0189] Example 40

[0190] Drug release experiment of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.2I:

[0191] Take 0.5 g of the 10P4L@0.2I solution described in Example 31 and add it to a glass release tube. Place it in a 37 °C water bath shaker for 15 min to gel it, and then slowly add 5 mL of preheated phosphate buffer (PBS). Regularly take out the upper release liquid and add 5 mL of new preheated PBS solution. Detect the concentration of the drug in the release sample by ultraviolet-visible spectrophotometer. The results show that the release period of iodine in the nano-composite gel drug sustained-release preparation is about 3 days.

[0192] Example 41

[0193] Drug release experiment of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.5I:

[0194] Take 0.5 g of the 10P4L@0.5I solution described in Example 34 and add it to a glass release tube. Place it in a 37 °C water bath shaker for 15 min to gel it. Then slowly add 5 mL of pre-warmed phosphate buffer solution (PBS). Regularly take out the upper layer of the release solution and add 5 mL of freshly pre-warmed PBS solution. Detect the concentration of the drug in the release sample by ultraviolet-visible spectrophotometer. The results show that the release period of iodine in the nano-composite gel drug sustained-release preparation is about 7 days.

[0195] Example 42

[0196] Drug release test of iodine-loaded nano-composite gel drug sustained-release preparation 10P4L@0.8I:

[0197] Take 0.5 g of the 10P4L@0.8I solution described in Example 37 and add it to a glass release tube. Place it in a 37 °C water bath shaker for 15 min to gel it. Then slowly add 5 mL of pre-warmed phosphate buffer solution (PBS). Regularly take out the upper layer of the release solution and add 5 mL of freshly pre-warmed PBS solution. Detect the concentration of the drug in the release sample by ultraviolet-visible spectrophotometer. The results show that the release period of iodine in the nano-composite gel drug sustained-release preparation is about 10 days.

[0198] Example 43

[0199] Antibacterial property test of iodine-loaded nano-composite gel drug sustained-release preparation:

[0200] Evaluate the antibacterial activity of iodine-loaded nano-composite gel through the inhibition zone experiment. Spread the bacterial suspensions of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (1×10 8 CFU / mL) evenly on LB agar plates respectively. After standing for 20 - 30 min, place 4 Oxford cups on each agar plate in turn, and inject the sterilized 10P4L@0.2I solution described in Example 31, the 10P4L@0.5I solution described in Example 34, the 10P4L@0.8I solution described in Example 37, and the 10P4L polymer solution described in Example 19. The amount of the injected liquid should be level with the top of the Oxford cup. Then incubate at 37 °C for 24 h. Use a 0.02 mm vernier caliper to measure the diameter of the inhibition zone, and repeat 3 times. The results show that for both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the diameter of the inhibition zone of the iodine-loaded groups is significantly higher than that of the non-iodine-loaded groups, indicating that the iodine-loaded nano-composite gel drug sustained-release preparation described in the present invention has excellent antibacterial activity. At the same time, the higher the iodine-loading concentration, the larger the diameter of the inhibition zone and the better the antibacterial effect.

[0201] Example 44

[0202] Coagulation-promoting performance test of iodine-loaded nano-composite gel drug sustained-release preparation:

[0203] The coagulation-promoting ability of the nano-composite gel was evaluated by detecting the whole blood coagulation time in contact with the surface of the nano-composite gel in a 96-well plate. The experimental groups were: blank group (without adding any materials), 10P0L nano-composite material described in Example 14, 10P3L nano-composite material described in Example 18, 10P4L nano-composite material described in Example 19, 10P5L nano-composite material described in Example 21, and 10P8L nano-composite material described in Example 23. Inject 200 μL of the polymer solution of each group into the bottom of the well plate and incubate in a water bath shaker at 37 °C for 15 min to form a gel in the nano-composite material group. Then add 50 μL of calcium ion-activated blood (1 mL of sodium citrate-anticoagulated rat whole blood mixed with 0.2 mol L -1 of CaCl2 solution). Timing starts when calcium ion-activated blood is added to all components. At specific time points, rinse the holes with physiological saline to stop coagulation. At the same time, immediately aspirate the upper liquid and rinse repeatedly until the solution is clear, indicating that all soluble blood components have been removed. Take pictures of each hole to confirm the time corresponding to the onset of coagulation for each group. The results show that the group without adding any materials coagulates in about 5 min. For the nano-composite materials, the addition of lithium alginate greatly shortens the coagulation time of the system, and the higher the content of lithium alginate, the shorter the coagulation time. This shows that the iodine-loaded nano-composite gel drug sustained-release preparation described in the present invention has good coagulation-promoting effects.

[0204] Example 45

[0205] Wound repair performance test of iodine-loaded nano-composite gel drug sustained-release preparation:

[0206] Study the application prospect of iodine-loaded nano-composite gel drug sustained-release preparation in wound repair. Using SD rats as an animal model, set up an experimental group (10P4L@0.5I described in Example 34) and a blank control group (physiological saline). After the rats were anesthetized, shave the hair on their backs and create a circular full-thickness wound with a diameter of 1 cm on their backs, and apply the materials of each group. Measure the wound size and take pictures at specific times. The results show that at the corresponding time points, the experimental group has smaller wound sizes, higher wound healing rates compared to the blank control group, and there is no exudate at the wound, and the repaired skin is smooth. This indicates the great potential of the iodine-loaded nano-composite gel drug sustained-release preparation described in the present invention as a wound repair material.

[0207] The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An iodine-loaded nano-composite gel drug sustained-release preparation, comprising 5-45 wt% of a nano-composite gel carrier material, 0.01-5 wt% of iodine element, and the balance of a solvent, characterized in that, The nano-composite gel carrier material comprises 25-95 wt% of an amphiphilic block copolymer and 75-5 wt% of hectorite; The amphiphilic block copolymer comprises 10-90 wt% of a hydrophilic block polyvinylpyrrolidone and 90-10 wt% of a hydrophobic block polyamino acid; The polyamino acid includes one or more of polyglycine, polyalanine, polyphenylalanine, poly(alanine- co -phenylalanine), polyglutamic acid, polylysine, polyaspartic acid, polyleucine, polytyrosine, and polyvaline; The solvent is pure water, a buffer solution, physiological saline, tissue culture medium, cell culture medium or animal and plant body fluid.

2. The iodine-loaded nano-composite gel drug sustained-release preparation according to claim 1, characterized in that, The average molecular weight of the hydrophilic block polyvinylpyrrolidone is 500-55000; The hydrophobic block polyamino acid monomer is an N-carboxy cyclic anhydride, and its structural general formula is: , wherein, R is , , , , , , , , , , .

3. The iodine-loaded nano-composite gel drug sustained-release preparation according to claim 1, wherein The hectorite is of one or several types of RD, XLG, D, RDS, XLS, XL21 or JS.

4. The iodine-loaded nano-composite gel drug sustained-release preparation according to claim 1, characterized in that, It further comprises 0.01-15 wt% of a regulator, and the regulator can be one or more of salts, sodium carboxymethylcellulose, iodinated glycerol, dimethicone, propylene glycol, carbomer, mannitol, sorbitol, Tween 20, Tween 40, Tween 80, xylitol, oligosaccharide, chondroitin, chitin, chitosan, collagen, gelatin, protein glue, hyaluronic acid, polyethylene glycol.

5. A preparation method of the iodine-loaded nano composite gel drug sustained-release preparation as described in claim 1, characterized in that, The amphiphilic block copolymer is rapidly dissolved in the solvent at low temperature, and the hectorite is added and mixed evenly to obtain the nano-composite gel carrier material, which is stored at low temperature for later use; before use, the nano-composite gel carrier material dissolved in the solvent is placed at low temperature and iodine is added and mixed evenly to obtain the gel sustained-release preparation; Or, The hectorite is dissolved in the solvent at low temperature, and the amphiphilic block copolymer is added and rapidly dissolved at low temperature to obtain the nano-composite gel carrier material, which is stored at low temperature for later use; before use, the nano-composite gel carrier material dissolved in the solvent is placed at low temperature and iodine is added and mixed evenly to obtain the gel sustained-release preparation; Or, The amphiphilic block copolymer is rapidly dissolved in the solvent at low temperature, the hectorite and iodine are added, and after dissolution and mixing, the gel sustained-release preparation is obtained, which is stored in the dark at low temperature for later use.

6. The preparation method according to claim 5, characterized in that, The preparation method of the amphiphilic block copolymer comprises: I. Preparation of amino-terminated polyvinylpyrrolidone: Take small molecule monomers vinylpyrrolidone and mercaptoethylamine and dissolve them in a toluene solvent. After complete dissolution, an initiator is added, and a free radical polymerization reaction is carried out for 24 h under an argon atmosphere; most of the toluene solvent is removed by rotary evaporation, the product is precipitated with a poor solvent, the upper clear liquid is poured off, and after vacuum drying for 24 h, the amino-terminated polyvinylpyrrolidone is obtained and put into the next reaction; II. Preparation of the amphiphilic block copolymer with polyvinylpyrrolidone as the hydrophilic block and polyamino acid as the hydrophobic block: The amino-terminated polyvinylpyrrolidone and a catalyst obtained above are dissolved in an anhydrous dichloromethane solvent, and a small molecule monomer N-carboxycyclic anhydride is added, and the reaction is carried out at room temperature for 24 h; most of the anhydrous dichloromethane solvent is removed by rotary evaporation, the product is precipitated with a poor solvent, the upper clear liquid is poured off, and after vacuum drying for 24 h, the above amphiphilic block copolymer is obtained.

7. Use of the iodine-loaded nano-composite gel drug sustained-release preparation as described in claim 1 in the preparation of drug delivery systems, antibacterial materials, hemostatic materials, wound repair materials, bone repair materials, embolizing agents and tissue adhesives.

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