Chitosan hollow microspheres and preparation method thereof

Abstract

The invention provides a chitosan hollow microsphere and a preparation method thereof, belongs to the technical field of high polymer materials, and solves the problems that the existing hollow microsphere preparation method is tedious and the raw material waste is serious. The preparation method comprises the following steps: providing a dispersing agent, a catalyst, a cross-linking agent, chitosan, hollow particles and water; mixing a catalyst, chitosan, hollow particles and water according to a first preset proportion to obtain a first solution; mixing a cross-linking agent, a dispersing agent and water according to a second preset proportion to obtain a second solution; mixing the first solution and the second solution according to a third preset proportion to obtain a third solution; and mixing the second solution and the third solution according to a fourth preset proportion, and drying to obtain the chitosan hollow microspheres. According to the scheme, the reaction in the preparation process is mild, no organic solvent is needed, the prepared hollow microspheres are uniform in particle size and high in yield, and the production efficiency is improved.

Description

Technical Field

[0001] The invention relates to the technical field of polymer materials, in particular to hollow chitosan microspheres and a preparation method thereof. Background Art

[0002] Chitosan is cheap and easy to obtain. It has multiple physiological functions such as hemostasis, antibacterial, and anti-cancer. It is non-toxic, non-irritating, and naturally degradable. It is widely used in tumor treatment, tissue engineering, drug delivery, water treatment, food packaging, etc. Making chitosan materials into hollow microspheres not only has the advantages of low density and light weight, but also increases the specific surface area of ​​chitosan, thereby improving its hemostasis and antibacterial properties.

[0003] At present, the methods for preparing hollow microspheres mainly include template method, spray drying method, electrostatic drop method, etc. For example, the shell polymer material is coated on the surface of polystyrene microspheres by emulsification crosslinking method to obtain core-shell structure microspheres with polystyrene microspheres as cores and gelatin, sodium alginate, chitosan and polylactic acid as shells, and the core polystyrene microspheres are soaked, dissolved and removed by tetrahydrofuran to obtain hollow microspheres. However, this method is not only cumbersome, but also requires a large amount of organic solvents and there is a waste of raw materials. Summary of the invention

[0004] The invention provides a chitosan hollow microsphere and a preparation method thereof, which solves the problems of complicated preparation method of hollow microsphere and serious waste of raw materials.

[0005] In order to solve the above technical problems, the technical solution of the present invention is as follows:

[0006] A method for preparing hollow chitosan microspheres, comprising:

[0007] providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water;

[0008] Mixing the catalyst, chitosan, hollow particles and water in a first preset ratio to obtain a first solution;

[0009] Mixing the crosslinking agent, the dispersant and water in a second preset ratio to obtain a second solution;

[0010] Mixing the first solution and the second solution in a third preset ratio to obtain a third solution;

[0011] The second solution and the third solution are mixed in a fourth preset ratio, and chitosan hollow microspheres are obtained after drying.

[0012] Optionally, the mass ratio of the dispersant, catalyst, cross-linking agent, chitosan, hollow particles and water is 1:(1-6):(3-18):(15-35):(15-30):(100-200).

[0013] Optionally, the step of mixing the catalyst, chitosan, hollow particles and water in a first preset ratio to obtain a first solution comprises:

[0014] The catalyst, chitosan, hollow particles and water are mixed in a mass ratio of (1-6): (15-35): (15-30): (75-150) to obtain a first solution.

[0015] Optionally, the mixing of the crosslinking agent, the dispersant and the water in a second preset ratio to obtain the second solution comprises:

[0016] The crosslinking agent, the dispersant and water are mixed in a mass ratio of (3-18):1:(25-50) to obtain a second solution.

[0017] Optionally, the molecular weight of the chitosan is 3000-30000, and the degree of deacetylation is 60%-90%; the dispersant is one or more of Tween 80, Tween 60, polyvinyl alcohol, polypyrrolidone, polyethylene glycol, OP-30, and triblock copolymer F127; the catalyst is one or more of acetic acid, phosphoric acid, nitric acid, and hydrochloric acid; the cross-linking agent is one or more of genipin, vanillin, glyoxal, glutaraldehyde, and hexaldehyde; the hollow particles are one or more of hollow silica microspheres, hollow glass microspheres, and hollow polymer microspheres; the surface functional groups of the hollow particles are one or more of epoxy, hydroxyl, and amino groups; and the diameter of the hollow particles is 2-100um.

[0018] Optionally, the first solution and the second solution are mixed in a third preset ratio to obtain a third solution, comprising:

[0019] The first solution and the second solution are mixed and stirred at 15° C. to 35° C. for 0.5 h to 1 h to obtain a third solution, wherein the mass ratio of the first solution to the second solution is (106-221): (10-23).

[0020] Optionally, the second solution and the third solution are mixed in a fourth preset ratio, and chitosan hollow microspheres are obtained after drying, comprising:

[0021] reacting the second solution with the third solution at 40° C. to 90° C. for 1 h to 6 h to obtain a fourth solution;

[0022] The fourth solution is centrifuged, washed with water, and dried to obtain hollow chitosan microspheres, wherein the mass ratio of the second solution to the third solution is (19-46): (116-244).

[0023] The embodiment of the present invention also provides a method for preparing hollow chitosan microspheres, comprising:

[0024] providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water;

[0025] The catalyst, chitosan, hollow particles and water are mixed in a mass ratio of 1:20:15:150 to obtain a first solution;

[0026] Mixing a crosslinking agent, a dispersant and water in a mass ratio of 6:1:50 to obtain a second solution;

[0027] The first solution and the second solution are mixed in a mass ratio of 186:23 to obtain a third solution;

[0028] The second solution and the third solution are mixed at a mass ratio of 27:209, and the chitosan hollow microspheres are obtained after drying.

[0029] The embodiment of the present invention further provides a chitosan hollow microsphere, and the chitosan hollow microsphere is prepared by the above method.

[0030] Optionally, the chitosan hollow microspheres have an average particle size of 18 μm, a particle size distribution of 1.347, and a density of 0.69 g / cm 3 , with a specific surface area of ​​451.8m 2 / kg.

[0031] The beneficial effects of the above technical solution of the present invention are:

[0032] The above-mentioned embodiment of the present invention provides a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water; mixes the catalyst, chitosan, hollow particles and water at a first preset ratio to obtain a first solution; mixes the cross-linking agent, dispersant and water at a second preset ratio to obtain a second solution; mixes the first solution and the second solution at a third preset ratio to obtain a third solution; mixes the second solution and the third solution at a fourth preset ratio, and obtains chitosan hollow microspheres after drying. The technical scheme uses a hollow template containing functional groups on the surface as a core layer carrier and chitosan as a coating layer. Through the cross-linking effect of an aldehyde cross-linking agent and functional groups (such as epoxy, hydroxyl, amine) on the hollow template and amino or hydroxyl groups on the chitosan molecular chain, chitosan is in situ coated on the surface of the hollow template to prepare chitosan hollow microspheres. The preparation process has a mild reaction and is free of organic solvents. The prepared hollow microspheres have uniform particle size and high yield, thereby improving production efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 1 is a schematic diagram of a process for preparing hollow chitosan microspheres according to an embodiment of the present invention;

[0034] Figure 2 is a diagram of the preparation process of hollow chitosan microspheres according to an embodiment of the present invention;

[0035] Among them, 1. chitosan hollow microspheres; 2. hollow particles; 3. chitosan coating layer. DETAILED DESCRIPTION

[0036] Embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0037] like Figure 1 As shown, the present invention provides a method for preparing hollow chitosan microspheres, comprising:

[0038] Step 11, providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water;

[0039] Step 12, mixing the catalyst, chitosan, hollow particles and water in a first preset ratio to obtain a first solution;

[0040] Step 13, mixing the crosslinking agent, the dispersant and water in a second preset ratio to obtain a second solution;

[0041] Step 14, mixing the first solution and the second solution in a third preset ratio to obtain a third solution;

[0042] Step 15: Mix the second solution and the third solution in a fourth preset ratio, and obtain hollow chitosan microspheres after drying.

[0043] In this embodiment of the present invention, a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water are weighed in a certain ratio, wherein the molecular weight of the chitosan is 3000-30000 and the degree of deacetylation is 60%-90%; the dispersant is one or more of Tween 80, Tween 60, polyvinyl alcohol, polypyrrolidone, polyethylene glycol, OP-30 and triblock copolymer F127, wherein when the dispersant is composed of multiple raw materials, it can include Tween 60 and triblock copolymer F127, or Tween 80 and polypyrrolidone, or Tween 80 and OP-30, or Tween 60 and polyvinyl alcohol, or Tween 60 and triblock copolymer F127 and polypyrrolidone, or polypyrrolidone and triblock copolymer F127; the catalyst is acetic acid, phosphorus The invention discloses a method for preparing a hollow particle of chitosan. The method comprises the following steps: mixing chitosan, a catalyst, hollow particles and 3 / 4 parts of water to prepare a first solution; mixing a crosslinking agent, a dispersant and 1 / 4 parts of water to prepare a second solution; taking 1 / 3 parts of the second solution and mixing and stirring with the first solution to obtain a third solution; adding the remaining 2 / 3 parts of the second solution to the third solution in three batches, and obtaining chitosan hollow microspheres after centrifugation, washing with water and drying.

[0044] This embodiment of the present invention uses a hollow template containing functional groups on the surface as a core layer carrier, and chitosan as a coating layer. Through the cross-linking effect of an aldehyde cross-linking agent and functional groups (such as epoxy, hydroxyl, and amine groups) on the hollow template and amino groups or hydroxyl groups on the chitosan molecular chain, chitosan is in situ coated on the surface of the hollow template to prepare chitosan hollow microspheres. The preparation process has a mild reaction and is free of organic solvents. The prepared hollow microspheres have uniform particle size and high yield, thereby improving production efficiency.

[0045] In some embodiments of the present invention, the mass ratio of the dispersant, catalyst, cross-linking agent, chitosan, hollow particles and water is 1: (1-6): (3-18): (15-35): (15-30): (100-200).

[0046] In some embodiments of the present invention, step 12 includes:

[0047] Step 121, mixing the catalyst, chitosan, hollow particles and water in a mass ratio of (1-6): (15-35): (15-30): (75-150) to obtain a first solution.

[0048] In some embodiments of the present invention, step 13 includes:

[0049] Step 131, mixing a cross-linking agent, a dispersant and water in a mass ratio of (3-18):1:(25-50) to obtain a second solution.

[0050] In some embodiments of the present invention, step 14 includes:

[0051] Step 141, mixing the first solution and the second solution at 15°C to 35°C and stirring for 0.5h to 1h to obtain a third solution.

[0052] In this embodiment of the present invention, the first solution and the second solution are mixed and stirred at 15°C to 35°C for 0.5h to 1h to obtain a third solution, wherein the mass ratio of the first solution to the second solution is (106-221): (10-23).

[0053] In some embodiments of the present invention, step 15 includes:

[0054] Step 151, reacting the second solution with the third solution at 40° C. to 90° C. for 1 h to 6 h to obtain a fourth solution;

[0055] Step 152, centrifuging, washing, and drying the fourth solution to obtain hollow chitosan microspheres.

[0056] In this embodiment of the present invention, the second solution and the third solution are reacted at 40°C to 90°C for 1h to 6h to obtain a fourth solution, wherein the mass ratio of the second solution to the third solution is (19-46):(116-244); the fourth solution is centrifuged, washed with water, and dried to obtain chitosan hollow microspheres.

[0057] The present invention also provides a method for preparing hollow chitosan microspheres, comprising:

[0058] Step 21, providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water;

[0059] Step 22, mixing the catalyst, chitosan, hollow particles and water in a mass ratio of 1:20:15:150 to obtain a first solution;

[0060] Step 23, mixing a crosslinking agent, a dispersant and water in a mass ratio of 6:1:50 to obtain a second solution;

[0061] Step 24, mixing the first solution and the second solution in a mass ratio of 186:23 to obtain a third solution;

[0062] Step 25, mixing the second solution and the third solution at a mass ratio of 27:209, and obtaining the chitosan hollow microspheres after drying.

[0063] The embodiment of the present invention further provides a chitosan hollow microsphere, wherein the chitosan hollow microsphere is prepared by the above method, wherein the chitosan hollow microsphere has an average particle size of 18 μm, a particle size distribution of 1.347, and a density of 0.69 g / cm 3 , with a specific surface area of ​​451.8m 2 / kg.

[0064] Example 1

[0065] This embodiment provides a method for preparing hollow chitosan microspheres, comprising:

[0066] Tween 80, acetic acid, glutaraldehyde, hollow glass microspheres rich in surface hydroxyl groups, chitosan (molecular weight of 6000, deacetylation degree of 85%) and water were weighed in a mass ratio of 1:1:3:16:20:150; the weighed chitosan, aminated hollow glass microspheres and acetic acid were mixed with 3 / 4 part of water to prepare a first solution; glutaraldehyde, Tween 80 and 1 / 4 part of water were mixed to prepare a second solution;

[0067] Take 1 / 3 of the second solution and mix it with the first solution at 25°C for 1 hour to obtain a third solution; add the remaining 2 / 3 of the second solution to the third solution within 1 hour, react at 60°C for 3 hours, filter, wash with water, and dry to obtain chitosan hollow microspheres with a particle size of about 21um and a yield of 85%.

[0068] Example 2

[0069] This embodiment provides a method for preparing hollow chitosan microspheres, comprising:

[0070] The triblock copolymer F127, acetic acid, genipin, aminated hollow silica microspheres, chitosan (molecular weight of 3000, degree of deacetylation of 85%) and water were weighed in a mass ratio of 1:4:9:25:10:200 respectively; the weighed chitosan, aminated hollow silica microspheres and acetic acid were mixed with 3 / 4 part of water to prepare a first solution; genipin, the triblock copolymer F127 and 1 / 4 part of water were mixed to prepare a second solution;

[0071] Take 1 / 3 of the second solution and mix it with the first solution at 35°C and stir for 0.5h to obtain a third solution; add the remaining 2 / 3 of the second solution to the third solution within 1h, react at 50°C for 3h, filter, wash with water, and dry to obtain chitosan hollow microspheres with a particle size of about 6um and a yield of 80%.

[0072] Example 3

[0073] This embodiment provides a method for preparing hollow chitosan microspheres, comprising:

[0074] Tween 60, phosphoric acid, vanillin, aminated hollow glass microspheres, chitosan (molecular weight of 10,000, degree of deacetylation of 90%) and water were weighed in a mass ratio of 1:2:15:20:20:100 respectively; the weighed chitosan, aminated hollow glass microspheres and phosphoric acid were mixed with 3 / 4 part of water to prepare a first solution; vanillin, Tween 60 and 1 / 4 part of water were mixed to prepare a second solution;

[0075] Take 1 / 3 of the second solution and mix it with the first solution at 15°C for 1 hour to obtain a third solution; add the remaining 2 / 3 of the second solution to the third solution within 1 hour, react at 60°C for 2 hours, filter, wash with water, and dry to obtain chitosan hollow microspheres with a particle size of about 10um and a yield of 92%.

[0076] Example 4

[0077] This embodiment provides a method for preparing hollow chitosan microspheres, comprising:

[0078] Tween 60, acetic acid, glyoxal, hydroxylated polymer hollow microspheres, chitosan (molecular weight of 15,000, deacetylation degree of 90%) and water are weighed in a mass ratio of 1:3:10:15:30:200 respectively; the weighed chitosan, hydroxylated polymer hollow microspheres and acetic acid are mixed with 3 / 4 part of water to prepare a first solution; glyoxal, Tween 60 and 1 / 4 part of water are mixed to prepare a second solution;

[0079] Take 1 / 3 of the second solution and mix it with the first solution at 35°C for 1 hour to obtain a third solution; add the remaining 2 / 3 of the second solution to the third solution within 1 hour, react at 80°C for 3 hours, filter, wash with water, and dry to obtain chitosan hollow microspheres with a particle size of about 18um and a yield of 85%.

[0080] Comparative Example 1

[0081] Compared with Examples 1 to 4, Comparative Example 1 is prepared without using a hollow template, and the specific steps are as follows:

[0082] Tween 80, acetic acid, glutaraldehyde, chitosan (molecular weight 6000, deacetylation degree 85%) and water were weighed in a mass ratio of 1:1:3:20:150; the weighed chitosan and acetic acid were mixed with 3 / 4 of water to prepare a first solution; glutaraldehyde, Tween 80 and 1 / 4 of water were mixed to prepare a second solution;

[0083] Take 1 / 3 of the second solution and mix it with the first solution at 25°C for 1 hour to obtain a third solution; add the remaining 2 / 3 of the second solution to the third solution within 1 hour, react at 60°C for 3 hours, and then filter, wash and dry to obtain chitosan particles with uneven particle size distribution.

[0084] The difference between Comparative Example 1 and Examples 1 to 4 is that Comparative Example 1 is prepared without using a hollow template.

[0085] The chitosan particles prepared in Examples 1 to 4 and Comparative Example 1 were tested for particle size, particle size distribution, specific surface area, and density. The test results are shown in Table 1.

[0086] As can be seen from Table 1, compared with Comparative Example 1, Examples 1 to 4 have narrow particle size distribution, low density, large specific surface area, and good application prospects because of the use of hollow templates for preparation.

[0087] Table 1 Performance comparison of Examples 1 to 4 and Comparative Example 1

[0088] Test samples Particle size / um Particle size distribution <![CDATA[Density (g / cm 3 )]]> <![CDATA[Specific surface area (m 2 / kg)]]> Example 1 21 1.967 0.63 540 Example 2 6 1.672 0.86 1016 Example 3 10 1.624 0.75 529.4 Example 4 18 1.347 0.69 451.8 Comparative Example 1 26 2.577 1.33 168.9

[0089] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific implementation", or "some implementations" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example.

[0090] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A method for preparing hollow chitosan microspheres, It is characterized in that include: providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water; Mixing the catalyst, chitosan, hollow particles and water in a first preset ratio to obtain a first solution; Mixing the crosslinking agent, the dispersant and water in a second preset ratio to obtain a second solution; Mixing the first solution and the second solution in a third preset ratio to obtain a third solution; The second solution and the third solution are mixed in a fourth preset ratio, and the chitosan hollow microspheres are obtained after drying.

2. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The mass ratio of the dispersant, catalyst, cross-linking agent, chitosan, hollow particles and water is 1: (1-6): (3-18): (15-35): (15-30): (100-200).

3. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The step of mixing the catalyst, chitosan, hollow particles and water in a first preset ratio to obtain a first solution comprises: The catalyst, chitosan, hollow particles and water are mixed in a mass ratio of (1-6): (15-35): (15-30): (75-150) to obtain a first solution.

4. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The step of mixing the crosslinking agent, the dispersant and the water in a second preset ratio to obtain a second solution comprises: The crosslinking agent, the dispersant and water are mixed in a mass ratio of (3-18):1:(25-50) to obtain a second solution.

5. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The molecular weight of the chitosan is 3000-30000, and the degree of deacetylation is 60%-90%; The dispersant is one or more of Tween 80, Tween 60, polyvinyl alcohol, polypyrrolidone, polyethylene glycol, OP-30, and triblock copolymer F127; The catalyst is one or more of acetic acid, phosphoric acid, nitric acid and hydrochloric acid; The cross-linking agent is one or more of genipin, vanillin, glyoxal, glutaraldehyde, and hexanedialdehyde; The hollow particles are one or more of hollow silica microspheres, hollow glass microspheres, and hollow polymer microspheres; The surface functional groups of the hollow particles are one or more of epoxy, hydroxyl and amino groups; The diameter of the hollow particles is 2-100 um.

6. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The first solution and the second solution are mixed in a third preset ratio to obtain a third solution, comprising: The first solution and the second solution are mixed and stirred at 15° C. to 35° C. for 0.5 h to 1 h to obtain a third solution, wherein the mass ratio of the first solution to the second solution is (106-221): (10-23).

7. The method for preparing hollow chitosan microspheres according to claim 1, It is characterized in that The second solution and the third solution are mixed in a fourth preset ratio, and chitosan hollow microspheres are obtained after drying, including: reacting the second solution with the third solution at 40° C. to 90° C. for 1 h to 6 h to obtain a fourth solution; The fourth solution is centrifuged, washed with water, and dried to obtain hollow chitosan microspheres, wherein the mass ratio of the second solution to the third solution is (19-46): (116-244).

8. A method for preparing hollow chitosan microspheres, It is characterized in that include: providing a dispersant, a catalyst, a cross-linking agent, chitosan, hollow particles and water; The catalyst, chitosan, hollow particles and water are mixed in a mass ratio of 1:20:15:150 to obtain a first solution; Mixing a crosslinking agent, a dispersant and water in a mass ratio of 6:1:50 to obtain a second solution; The first solution and the second solution are mixed in a mass ratio of 186:23 to obtain a third solution; The second solution and the third solution are mixed at a mass ratio of 27:209, and the chitosan hollow microspheres are obtained after drying.

9. A chitosan hollow microsphere, It is characterized in that The chitosan hollow microspheres are prepared by the method according to any one of claims 1 to 8.

10. The hollow chitosan microspheres according to claim 9, It is characterized in that The average particle size of the chitosan hollow microspheres is 18 μm, the particle size distribution is 1.347, and the density is 0.69 g / cm 3 , with a specific surface area of ​​451.8m 2 / kg.

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