Anisotropic hydrogel material and method of making the same

Abstract

The present application relates to a kind of anisotropic hydrogel material and its preparation method;Formulate the solution containing monomer, crosslinking agent, photoinitiator, polyamino acid ester with alpha-helix structure and solvent;By shear force or magnetic field effect makes polyamino acid ester molecule in solution orientation form nematic liquid crystal, obtain the solution with orientation structure;After photoinitiation polymerization, obtain polyamino acid ester composite gel;Composite gel is hydrolyzed in hydrogen bromide acetic acid solution, and polyamino acid ester with alpha-helix structure is hydrolyzed into polyamino acid with alpha-helix structure, obtain the anisotropic hydrogel with pH sensitivity.The anisotropic hydrogel material is composed of polyamino acid with alpha-helix structure and ordinary hydrogel matrix.Polyamino acid embedded in hydrogel matrix forms highly oriented liquid crystal structure.The anisotropic hydrogel has higher anisotropy index, generally greater than 2.The anisotropic hydrogel material prepared by the present application is applied to embolization agent.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of composite materials and high molecular functional materials, and particularly relates to an anisotropic hydrogel material and a preparation method. BACKGROUND

[0002] Synthetic hydrogels have many structural similarities with biological tissues, and have good biocompatibility, and are often used in artificial tissues and organs and other biomedical fields. There are also significant differences between the two in structure and performance. In particular, synthetic hydrogels often have isotropic structure and performance, while biological tissues such as muscle, cartilage and tendon often have anisotropic structure and performance. Swelling is the most important property of hydrogels. Many hydrogels can respond to external stimuli and change their swelling degree under the action of external stimuli, and are important intelligent soft materials. Due to the isotropic structure of ordinary hydrogels, their swelling in all directions is usually the same, showing isotropic swelling behavior.

[0003] Anisotropic hydrogels are a new type of hydrogels inspired by the unique structure and properties of biological tissues. These hydrogels also have anisotropic structure, thus exhibit various anisotropic properties, such as anisotropic mechanical properties, anisotropic swelling properties, etc. Anisotropic hydrogels with anisotropic swelling properties, especially capable of anisotropic swelling under external stimuli, have many important uses. Amir H. Milani et al. disclosed anisotropic hydrogels composed of oriented rod-like particles and a hydrogel matrix. The rod-like particles include worm-like triblock copolymer micelles, self-assembled β-sheeted polypeptide fibers, and microcrystalline cellulose fibers. The hydrogel matrix is a cross-linked pH-sensitive nanogel. These anisotropic hydrogels undergo anisotropic swelling under pH stimuli, but the anisotropy index (the ratio of the swelling degree in the perpendicular orientation direction to that in the parallel orientation direction) is small, only 1.11-1.31. (A. H. Milani, et al. Anisotropic pH-Responsive Hydrogels Containing Soft or Hard Rod-Like Particles Assembled Using Low Shear, Chemistry of Materials, 2017, 29(7), 3100-3110) Dai et al. disclosed an anisotropic hydrogel composed of oriented magnetic double-layer nanosheets and a temperature-sensitive poly-N-isopropylacrylamide hydrogel matrix. The hydrogel undergoes anisotropic swelling under temperature stimuli, but the anisotropy index is only 1.125. (C. F. Dai, et al. Magneto-Orientation of Magnetic Double Stacks for Patterned Anisotropic Hydrogels with Multiple Responses and Modulable Motions, Angewandte Chemie International Edition, 2022. 61(35): p. e202207272.) J. M. Boothby et al. disclosed anisotropic hydrogels composed of oriented lyotropic chromonic liquid crystals and a temperature-sensitive poly-N-isopropylacrylamide hydrogel matrix or a pH-sensitive polyacrylic acid hydrogel matrix. The hydrogel undergoes anisotropic swelling under temperature or pH stimuli, but the anisotropy index is only 1.26.(J.M. Boothby, et al., Molecularly-ordered hydrogels with controllable, anisotropic stimulus response, Soft Matter, 2019. 15(22): p. 4508-4517.).

[0004] Existing anisotropic hydrogels that can be anisotropically swollen under external stimuli are composed of two parts. One is the oriented nanofiller, such as the aforementioned worm-like triblock copolymer micelles, self-assembled β-sheet polypeptide fibers, microcrystalline cellulose fibers, magnetic bilayer nanosheets, and lyotropic chromonic liquid crystals. The other is the stimulus-responsive hydrogel matrix, such as the aforementioned temperature-sensitive poly-N-isopropylacrylamide hydrogel matrix or pH-sensitive polyacrylic acid hydrogel matrix. The former provides an oriented structure, and the latter stabilizes the oriented structure of the former and makes the hydrogel stimulus-responsive. In addition, the anisotropy index of most anisotropic hydrogels is small, which is difficult to meet the actual needs. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application proposes a pH-sensitive anisotropic hydrogel constructed with polyamino acid with α-helix structure as filler and ordinary hydrogel matrix. The anisotropic hydrogel material comprises two parts of oriented polyamino acid with α-helix structure and ordinary hydrogel matrix. Here, the polyamino acid is a molecule, which has a larger specific surface area than a nanoparticle, and thus can produce a greater restriction on the movement of chain segments during hydrogel swelling.

[0006] The technical scheme of the present application is as follows:

[0007] An anisotropic hydrogel material composed of polyamino acid with α-helix structure and ordinary hydrogel matrix.

[0008] A preparation method of an anisotropic hydrogel material, characterized by comprising the following steps:

[0009] (1) preparing a solution containing monomers, crosslinking agents, photoinitiators, polyamino acid esters with α-helix structure, and solvents;

[0010] (2) orienting the polyamino acid ester molecules in the solution obtained in step (1) by shear force or magnetic field to form a nematic liquid crystal, and obtaining a solution with oriented structure;

[0011] (3) polymerizing the solution obtained in step (2) by light initiation to obtain a polyamino acid ester composite gel;

[0012] (4) hydrolyzing the composite gel obtained in step (3) in a hydrogen bromide acetic acid solution to hydrolyze the polyamino acid ester with α-helix structure into polyamino acid with α-helix structure, and obtaining the anisotropic hydrogel with pH sensitivity.

[0013] The polyamino acid ester with α-helix structure includes polybenzyl glutamate, polytert-butyl glutamate, polybenzyl lysine, polytert-butyl lysine, poly(benzyl glutamate-alanine) copolymer, poly(tert-butyl glutamate-alanine) copolymer, poly(benzyl lysine-alanine) copolymer or poly(tert-butyl lysine-alanine) copolymer; the concentration of the polyamino acid ester with α-helix structure in the solution is 0.1-0.5 g / mL.

[0014] The monomer includes one or two of acrylamide, N,N-dimethyl acrylamide, N,N-diethyl acrylamide and N-phenyl acrylamide; the concentration of the monomer in the solution is 0.05-0.5 g / mL.

[0015] The crosslinking agent includes N,N'-methylene bisacrylamide or ethylene glycol diacrylate; the concentration of the crosslinking agent in the solution is 0.001-0.01 g / mL.

[0016] The photoinitiator includes 2,2-diethoxyacetophenone, benzildeneacetone, Darocur 1173 or Irgacure-184; the concentration of the photoinitiator in the solution is 0.001-0.05 mg / mL.

[0017] The solvent includes dioxane, N,N-dimethylformamide or dimethyl sulfoxide.

[0018] The shear force is to generate two parallel but opposite forces; preferably by extruding the solution into a small caliber tube or scraping the solution in one direction by a scraper.

[0019] The concentration of the hydrogen bromide acetic acid solution in step (4) is 15-35 wt%, and the hydrolysis time is preferably 4-8 hours.

[0020] The anisotropic hydrogel material prepared by the application is applied to embolization agents.

[0021] The anisotropic hydrogel material obtained by the application includes two parts of oriented polyamino acid with α-helix structure and hydrogel matrix.

[0022] The application utilizes the polyamino acid with α-helix structure generated by hydrolyzing the polyamino acid ester with α-helix structure, and the polyamino acid with α-helix structure is polyglutamic acid, polylysine, polyalanine, polyglutamic acid-alanine copolymer or polylysine-alanine copolymer.

[0023] The anisotropic hydrogel material obtained by the present application has pH sensitivity and anisotropic swelling. When the anisotropic hydrogel is placed in a buffer solution with different pH, the axial and radial swelling degrees of the anisotropic hydrogel change obviously with the change of pH.

[0024] Meanwhile, the axial swelling degree S ⊥ of the anisotropic hydrogel is greater than the radial swelling degree S ‖ , and the anisotropy index is generally greater than 2.

[0025] Advantages and excellent effects: The anisotropic hydrogel material obtained by the present application is composed of oriented polyamino acid with α-helix structure and common hydrogel matrix. The polyamino acid embedded in the hydrogel matrix forms a highly oriented liquid crystal structure. When the anisotropic hydrogel material is placed in a buffer solution with different pH, the axial and radial swelling degrees of the anisotropic hydrogel change obviously with the change of pH. Since the polyamino acid has pH sensitivity, the anisotropic hydrogel material has pH sensitivity without cooperation with a stimulus-responsive hydrogel matrix, and can swell anisotropically under pH stimulation. More importantly, the anisotropy index of the anisotropic hydrogel material is high, generally greater than 2. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 : The axial and radial swelling degrees of the polyglutamic acid composite hydrogel prepared in Example 1 under different pH conditions. When pH > 5.5, the axial swelling degree S ⊥ of the hydrogel is greater than the radial swelling degree S ‖ , and the swelling anisotropy index (S ⊥ / S ∥ ) under different pH is generally greater than 3. The polyglutamic acid composite hydrogel has pH sensitivity.

[0027] Figure 2 : The pH stimulation swelling kinetics of the polyglutamic acid composite hydrogel prepared in Example 1. The axial swelling degree S ⊥ of the hydrogel is greater than the radial swelling degree S ‖ . The swelling anisotropy index (S ⊥ / S ∥ ) is 3.4.

[0028] Figure 3 : The polarizing microscope photos of the polyglutamic acid composite hydrogel prepared in Example 1 in a pH 3.4 buffer solution and a pH 7.4 buffer solution, respectively. The change of pH causes the gel to swell obviously, and the axial swelling degree of the hydrogel is obviously greater than the radial swelling degree. The banded texture structure indicates that the polyglutamic acid in the hydrogel is in a nematic liquid crystal structure. DETAILED DESCRIPTION

[0029] The application will be further described in detail below with reference to the accompanying drawings and specific examples.

[0030] Example 1:

[0031] 1) 1.5 g (0.15 g / mL) of N,N-dimethylacrylamide, 0.5 g (0.05 g / mL) of N-phenylacrylamide, 0.05 g (0.005 g / mL) of N,N'-methylenebisacrylamide, 100 μL (0.01 mg / mL) of 2,2-diethoxyacetophenone, and 2.0 g (0.2 g / mL) of poly (benzyl glutamate) were dissolved in 10.0 mL of 1,4-dioxane to form a solution.

[0032] 2) The solution of step 1 was injected into a capillary tube with an inner diameter of 0.5 mm, so that the poly (benzyl glutamate) formed a nematic liquid crystal.

[0033] 3) The solution of step 2 was subjected to 4 h of ultraviolet light irradiation to obtain a poly (benzyl glutamate) composite gel.

[0034] 4) The poly (benzyl glutamate) composite gel obtained in step 3 was treated in a 35 wt% hydrogen bromide acetic acid solution for 4 h to remove the benzyl group on the poly (benzyl glutamate). The obtained poly (glutamic acid) composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0035] The poly (glutamic acid) composite hydrogel was placed in buffer solutions with different pH (5.5, 6.5, 7.4, 8.5), and it was observed that the axial and radial swelling degrees of the hydrogel changed obviously with increasing pH. The poly (glutamic acid) hydrogel has pH sensitivity. When the pH is greater than 5.5, the axial swelling degree S ⊥ of the hydrogel is greater than the radial swelling degree S ‖ . The swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel under different pH is generally greater than 3, as shown in the accompanying drawings. Figure 1 .

[0036] The poly (glutamic acid) composite hydrogel was transferred from a pH 3.4 buffer solution to a pH 7.4 buffer solution, and it was observed that the gel swelled obviously due to the change in pH, and the axial swelling degree of the hydrogel was obviously greater than the radial swelling degree, as shown in the accompanying drawings. Figure 2 The axial (S ⊥ =l ⊥,pH7.4 / l ⊥,pH3.4 ) and radial (S ‖ =l ‖,pH7.4 / l ‖,pH3.4 ) swelling degrees of the hydrogel were determined, and the swelling anisotropy index (S ⊥ / S ∥) is 3.43. The swelling anisotropy index is much larger than that of most stimuli-responsive anisotropic hydrogels. The photographs of the polyglutamic acid composite hydrogel in pH 3.4 buffer solution and pH 7.4 buffer solution, respectively, were taken by polarizing microscope, see the photographs in the description attached Figure 3 The banded texture structure can be clearly seen, indicating that the polyglutamic acid in the hydrogel is in a nematic liquid crystal structure.

[0037] Example 2:

[0038] 1) 2.0 g (0.2 g / mL) of N,N-dimethylacrylamide, 0.5 g (0.05 g / mL) of N-phenylacrylamide, 0.1 g (0.01 g / mL) of N,N'-methylenebisacrylamide, 100 μL (0.01 mg / mL) of 2,2-diethoxyacetophenone, and 2.5 g (0.25 g / mL) of polyglutamic acid benzyl ester were dissolved in 10.0 mL of dimethyl sulfoxide to form a solution.

[0039] 2) The solution of step 1 was scraped into a thin layer with a thickness of 0.5 mm by a film scraper, so that the polyglutamic acid benzyl ester formed a nematic liquid crystal.

[0040] 3) The solution of step 2 was subjected to 24 h ultraviolet light irradiation to obtain a polyglutamic acid benzyl ester composite gel.

[0041] 4) The polyglutamic acid benzyl ester composite gel obtained in step 3 was treated in 35 wt% hydrogen bromide acetic acid solution for 4 h to remove the benzyl group on the polyglutamic acid benzyl ester. The obtained polyglutamic acid composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0042] When the polyglutamic acid composite hydrogel was transferred from the pH 3.4 buffer solution to the pH 7.4 buffer solution, it was observed that the gel swelled obviously due to the change in pH. The swelling degree of the hydrogel in the axial direction (S ⊥ = l ⊥,pH7.4 / l ⊥,pH3.4 ) and the radial direction (S ‖ = l ‖,pH7.4 / l ‖,pH3.4 ) were measured, and the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated to be 3.07.

[0043] Example 3:

[0044] 1) 2.0 g (0.2 g / mL) of N,N-dimethylacrylamide, 0.5 g (0.05 g / mL) of N,N-diethylacrylamide, 0.05 g (0.005 g / mL) of ethylene glycol diacrylate, 100 μL (0.01 mg / mL) of Darocur 1173, and 3.0 g (0.3 g / mL) of poly (L-glutamic acid tert-butyl ester) were dissolved in 10.0 mL of 1,4-dioxane to form a solution.

[0045] 2) The solution of step 1 was placed in a 1 T magnetic field for 24 hours to make the poly (L-glutamic acid tert-butyl ester) form a nematic liquid crystal.

[0046] 3) The solution of step 2 was subjected to 8 h of ultraviolet light to obtain a poly (L-glutamic acid tert-butyl ester) composite gel.

[0047] 4) The poly (L-glutamic acid tert-butyl ester) composite gel obtained in step 3 was treated in a 30 wt% hydrogen bromide acetic acid solution for 5 h to remove the tert-butyl group on the poly (L-glutamic acid tert-butyl ester). The obtained poly (L-glutamic acid) composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0048] The poly (L-glutamic acid) composite hydrogel was transferred from the pH 3.4 buffer solution to a pH 7.4 buffer solution, and a significant swelling of the gel due to the change in pH was observed. The swelling degree of the hydrogel in the axial direction (S ⊥ = l ⊥,pH7.4 / l ⊥,pH3.4 ) and the radial direction (S ‖ = l ‖,pH7.4 / l ‖,pH3.4 ) was measured, and the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated to be 3.21.

[0049] Example 4:

[0050] 1) 5 g (0.5 g / mL) of acrylamide, 0.1 g (0.01 g / mL) of N,N'-methylenebisacrylamide, 10 μL (0.001 mg / mL) of 2,2-diethoxyacetophenone, and 1.0 g (0.1 g / mL) of poly (L-lysine benzyl ester) were dissolved in 10.0 mL of 1,4-dioxane to form a solution.

[0051] 2) The solution of step 1 was injected into a capillary tube with an inner diameter of 1 mm to make the poly (L-lysine benzyl ester) form a nematic liquid crystal.

[0052] 3) The solution of step 2 was subjected to 4 h of ultraviolet light to obtain a poly (L-lysine benzyl ester) composite gel.

[0053] 4) The polylysine-benzyl ester composite hydrogel obtained in step 3 was treated in 15 wt% hydrogen bromide-acetic acid solution for 8 h to remove the benzyl groups on the polylysine-benzyl ester. The obtained polylysine composite hydrogel was washed thoroughly in water and then placed in a pH 10.5 buffer solution.

[0054] The polylysine composite hydrogel was transferred from the pH 10.5 buffer solution to a pH 7.4 buffer solution. It was observed that the gel swelled significantly due to the change in pH. The swelling degree of the hydrogel in the axial direction (S ⊥ = 1 ⊥,pH7.4 / 1 ⊥,pH10.5 ) and the radial direction (S ‖ = 1 ‖,pH7.4 / 1 ‖,p10.5 ) was measured, and the anisotropy index of the swelling of the hydrogel (S ⊥ / S ∥ ) was calculated to be 2.49.

[0055] Example 5:

[0056] 1) 0.5 g (0.025 g / mL) of N,N-dimethylacrylamide, 0.5 g (0.025 g / mL) of N-phenylacrylamide, 0.02 g (0.001 g / mL) of N,N'-methylenebisacrylamide, 500 μL (0.025 mg / mL) of 2,2-diethoxyacetophenone, and 10.0 g (0.5 g / mL) of poly(glutamic acid-alanine) benzyl ester were dissolved in 20.0 mL of dimethyl sulfoxide to prepare a solution.

[0057] 2) The solution of step 1 was injected into a glass tube with an inner diameter of 10 mm, and the poly(glutamic acid-alanine) benzyl ester was formed into a nematic phase liquid crystal.

[0058] 3) The solution of step 2 was subjected to ultraviolet light for 12 h to obtain a poly(glutamic acid-alanine) benzyl ester composite hydrogel.

[0059] 4) The poly(glutamic acid-alanine) benzyl ester composite hydrogel obtained in step 3 was treated in 20 wt% hydrogen bromide-acetic acid solution for 6 h to remove the benzyl groups on the poly(glutamic acid-alanine) benzyl ester. The obtained poly(glutamic acid-alanine) composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0060] The poly(glutamic acid-alanine) composite hydrogel was transferred from the pH 3.4 buffer solution to a pH 7.4 buffer solution. It was observed that the gel swelled significantly due to the change in pH. The swelling degree of the hydrogel in the axial direction (S ⊥ = 1 ⊥,pH7.4 / 1 ⊥,pH3.4) and the radial swelling degree (S ‖ = 1 ‖,pH7.4 / l ‖,pH3.4 ), the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated as 2.19.

[0061] Example 6:

[0062] 1) 2.0 g (0.2 g / mL) of N, N-diethylacrylamide, 1.0 g (0.1 g / mL) of N-phenylacrylamide, 0.1 g (0.01 g / mL) of ethylene glycol diacrylate, 300 μL (0.03 mg / mL) of benzophenone, and 2.0 g (0.2 g / mL) of poly (tert-butyl glutamate) were dissolved in 10.0 mL of 1, 4-dioxane to prepare a solution.

[0063] 2) The solution of step 1 was injected into a glass tube with an inner diameter of 5 mm, and the poly (tert-butyl glutamate) formed a nematic liquid crystal.

[0064] 3) The solution of step 2 was subjected to UV light for 10 h to obtain a poly (tert-butyl glutamate) composite gel.

[0065] 4) The poly (tert-butyl glutamate) composite gel obtained in step 3 was treated in a 30 wt% hydrogen bromide acetic acid solution for 5 h to remove the tert-butyl group on the poly (tert-butyl glutamate). The obtained poly (glutamic acid) composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0066] When the poly (glutamic acid) composite hydrogel was transferred from the pH 3.4 buffer solution to a pH 7.4 buffer solution, a significant swelling of the gel due to the change in pH was observed. The axial swelling degree (S ⊥ = 1 ⊥,pH7.4 / l ⊥,pH3.4 ) and the radial swelling degree (S ‖ = 1 ‖,pH7.4 / l ‖,pH3.4 ), the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated as 2.77.

[0067] Example 7:

[0068] 1) Dissolve 1.0 g (0.1 g / mL) of N,N-dimethylacrylamide, 1.5 g (0.15 g / mL) of N-phenylacrylamide, 0.03 g (0.003 g / mL) of N,N'-methylenebisacrylamide, 100 μL (0.01 mg / mL) of 2,2-diethoxyacetophenone, and 2.5 g (0.25 g / mL) of poly(L-lysine-L-alanine tert-butyl ester) in 10.0 mL of 1,4-dioxane to make a solution.

[0069] 2) Inject the solution from Step 1 into a capillary tube with an inner diameter of 2 mm to form a nematic phase liquid crystal of poly(L-lysine-L-alanine tert-butyl ester).

[0070] 3) Subject the solution from Step 2 to UV light for 6 h to obtain a poly(L-lysine-L-alanine tert-butyl ester) composite gel.

[0071] 4) Treat the poly(L-lysine-L-alanine tert-butyl ester) composite gel from Step 3 in 20 wt% hydrogen bromide acetic acid solution for 6 h to remove the tert-butyl groups from the poly(L-lysine-L-alanine tert-butyl ester). The resulting poly(L-lysine-L-alanine) composite hydrogel is washed thoroughly in water and then placed in a pH 8.5 buffer solution.

[0072] Upon transferring the poly(L-lysine-L-alanine) composite hydrogel from the pH 8.5 buffer solution to a pH 5.5 buffer solution, a significant swelling of the gel due to the change in pH is observed. The swelling degree of the hydrogel in the axial direction (S ⊥ = l ⊥,pH5.5 / l ⊥,pH8.5 ) and the radial direction (S ‖ = l ‖,pH5.5 / l ‖,pH8.5 ) is measured, and the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel is calculated to be 2.15.

[0073] Example 8:

[0074] 1) Dissolve 3.0 g (0.3 g / mL) of N,N-diethylacrylamide, 0.01 g (0.001 g / mL) of N,N'-methylenebisacrylamide, 200 μL (0.02 mg / mL) of 2,2-diethoxyacetophenone, and 2.0 g (0.2 g / mL) of poly(L-glutamic acid-L-alanine tert-butyl ester) in 10.0 mL of N,N-dimethylformamide to make a solution.

[0075] 2) Use a film applicator to apply the solution from Step 1 as a 0.3 mm film to form a nematic phase liquid crystal of poly(L-glutamic acid-L-alanine tert-butyl ester).

[0076] 3) The solution from step 2 was exposed to UV light for 12 h to obtain a poly(glutamic acid-alanine) t-butyl ester composite hydrogel.

[0077] 4) The poly(glutamic acid-alanine) t-butyl ester composite hydrogel from step 3 was treated in 33 wt% hydrogen bromide acetic acid solution for 4 h to remove the t-butyl groups from the poly(glutamic acid-alanine) t-butyl ester. The resulting poly(glutamic acid-alanine) composite hydrogel was washed thoroughly in water and then placed in a pH 3.4 buffer solution.

[0078] Upon transferring the poly(glutamic acid-alanine) composite hydrogel from the pH 3.4 buffer solution to a pH 7.4 buffer solution, a significant swelling of the gel was observed due to the change in pH. The swelling degree of the hydrogel in the axial direction (S ⊥ = l ⊥,pH7.4 / l ⊥,pH3.4 ) was significantly greater than the swelling degree in the radial direction (S ‖ = l ‖,pH7.4 / l ‖,pH3.4 ). The swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated to be 2.50.

[0079] Example 9:

[0080] 1) 1.0 g (0.1 g / mL) of acrylamide, 0.05 g (0.005 g / mL) of N,N'-methylenebisacrylamide, 200 μL (0.02 mg / mL) of Darocur 1173, and 4.0 g (0.4 g / mL) of polylysine t-butyl ester were dissolved in 10.0 mL of 1,4-dioxane to form a solution.

[0081] 2) The solution from step 1 was injected into a capillary tube with an inner diameter of 2 mm, and the polylysine t-butyl ester formed a nematic phase liquid crystal.

[0082] 3) The solution from step 2 was exposed to UV light for 4 h to obtain a polylysine t-butyl ester composite hydrogel.

[0083] 4) The polylysine t-butyl ester composite hydrogel from step 3 was treated in 33 wt% hydrogen bromide acetic acid solution for 4 h to remove the t-butyl groups from the polylysine t-butyl ester. The resulting polyglutamic acid composite hydrogel was washed thoroughly in water and then placed in a pH 10.5 buffer solution.

[0084] Upon transferring the polyglutamic acid composite hydrogel from the pH 10.5 buffer solution to a pH 7.4 buffer solution, a significant swelling of the gel was observed due to the change in pH. The swelling degree of the hydrogel in the axial direction (S ⊥ = l⊥,pH7.4 / l ⊥,pH10.5 ) and the radial swelling degree (S ‖ = l ‖,pH7.4 / l ‖,pH10.5 ), the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated to be 2.90.

[0085] Example 10:

[0086] 1) 1.5 g (0.15 g / mL) of N,N-diethylacrylamide, 0.5 g (0.05 g / mL) of N-phenylacrylamide, 0.1 g (0.01 g / mL) of N,N'-ethylene glycol diacrylate, 0.50 mg (0.05 mg / mL) of Irgacure-184 and 3 g (0.3 g / mL) of poly(lysine-alanine) benzyl ester were dissolved in 10.0 mL of 1,4-dioxane to form a solution.

[0087] 2) The solution of step 1 was injected into a capillary tube with an inner diameter of 0.5 mm, so that the poly(lysine-alanine) benzyl ester formed a nematic liquid crystal.

[0088] 3) The solution of step 2 was subjected to 2 h ultraviolet light irradiation to obtain a poly(lysine-alanine) benzyl ester composite gel.

[0089] 4) The poly(lysine-alanine) benzyl ester composite gel obtained in step 3 was treated in 33 wt% hydrogen bromide acetic acid solution for 4 h to remove the benzyl group on the poly(lysine-alanine) benzyl ester. The obtained poly(lysine-alanine) composite hydrogel was washed thoroughly in water and then placed in a pH 8.5 buffer solution.

[0090] The poly(lysine-alanine) composite hydrogel was transferred from the pH 8.5 buffer solution to a pH 5.5 buffer solution, and it was observed that the gel swelled obviously due to the change in pH. The axial swelling degree (S ⊥ = l ⊥,pH5.5 / l ⊥,pH8.5 ) and the radial swelling degree (S ‖ = l ‖,pH5.5 / l ‖,pH8.5 ), the swelling anisotropy index (S ⊥ / S ∥ ) of the hydrogel was calculated to be 3.15.

[0091] Example 11:

[0092] The anisotropic gel obtained in the application is subjected to a blood vessel embolization experiment. Six rabbits weighing 2 kg are selected, and three rabbits are grouped into a control group and an experimental group. The rabbits in the control group are not subjected to any treatment. The rabbits in the experimental group are subjected to the following treatment: the fur on the outer side of the rabbit's auricle is removed, and the rabbit's auricle is cleaned with alcohol, and the rabbit is anesthetized by intravenous injection of a 1.5% sodium pentobarbital solution along the auricular margin. After the animal enters a state of anesthesia, the central branch of the auricular artery of the rabbit is blocked by clamping with an arterial clamp, and an anisotropic gel sample with a diameter of 0.2 mm and a length of 20 mm is implanted into the central artery of the rabbit's auricle. After the animal wakes up, it is placed in a cage for normal feeding.

[0093] After embolization for 1 day, the rabbit's auricle in the experimental group and the control group is subjected to photography and infrared thermal imaging, respectively. By comparing the photographs of the rabbit's auricle in the two groups, it can be found that there is no obvious change in the control group, and the embolized rabbit's auricle in the experimental group is obviously different from the surrounding blood vessels, and the anisotropic swollen gel can be seen to expand the blood vessels. By comparing the thermal imaging images of the two groups, it can be obviously observed that the temperature of the rabbit's auricle in the control group is high, and there is an obvious blood vessel thermal image; the temperature of the rabbit's auricle in the experimental group is obviously reduced, and the embolization of the central artery of the rabbit's auricle leads to a significant reduction in blood flow, and no blood vessel thermal image can be observed on the rabbit's auricle.

[0094] The above experimental results show that the anisotropic gel has obvious blood vessel embolization effect.

[0095] The technical solutions disclosed and proposed in the application can be implemented by referring to the content of the present application, appropriately changing the conditions and routes, etc. Although the methods and preparation techniques of the present application have been described by means of preferred embodiments, it is obvious to those skilled in the art that the methods and technical routes described herein can be modified or recombined without departing from the content, spirit and scope of the present application, to realize the final preparation technique. It is particularly pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they are considered to be included in the spirit, scope and content of the present application.

Claims

1. An anisotropic hydrogel material, characterized in that, It is composed of oriented polyamino acids with α-helical structures and a hydrogel matrix; the preparation method includes the following steps: (1) Prepare a solution containing monomers, crosslinking agents, photoinitiators, polyamino acid esters with α-helical structures, and solvents; (2) The polyamino acid ester molecules in the solution obtained in step (1) are oriented by shear force or magnetic field to form a nematic liquid crystal, thus obtaining a solution with an oriented structure; (3) The solution obtained in step (2) is subjected to photo-initiated polymerization to obtain a polyamino acid ester composite gel; (4) The composite gel obtained in step (3) is hydrolyzed in a solution of bromoacetic acid. The polyamino acid ester with an α-helical structure is hydrolyzed into a polyamino acid with an α-helical structure, resulting in an anisotropic hydrogel with pH sensitivity.

2. The method for preparing anisotropic hydrogel material according to claim 1, characterized in that, Includes the following steps: (1) Prepare a solution containing monomers, crosslinking agents, photoinitiators, polyamino acid esters with α-helical structures, and solvents; (2) The polyamino acid ester molecules in the solution obtained in step (1) are oriented by shear force or magnetic field to form a nematic liquid crystal, thus obtaining a solution with an oriented structure; (3) The solution obtained in step (2) is subjected to photo-initiated polymerization to obtain a polyamino acid ester composite gel; (4) The composite gel obtained in step (3) is hydrolyzed in a solution of bromoacetic acid. The polyamino acid ester with an α-helical structure is hydrolyzed into a polyamino acid with an α-helical structure, resulting in an anisotropic hydrogel with pH sensitivity.

3. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, Polyamino acid esters with an α-helical structure include polybenzyl glutamate, polytert-butyl glutamate, polybenzyl lysine, polytert-butyl lysine, poly(glutamate-alanine) benzyl ester copolymer, poly(glutamate-alanine) tert-butyl ester copolymer, poly(lysine-alanine) benzyl ester copolymer, or poly(lysine-alanine) tert-butyl ester copolymer; the concentration of the polyamino acid ester with an α-helical structure in solution is 0.1-0.5 g / mL.

4. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, The monomers include one or two of acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-phenylacrylamide; the concentration of the monomers in the solution is 0.05-0.5 g / mL.

5. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, The crosslinking agent includes N,N'-methylenebisacrylamide or ethylene glycol diacrylate; the concentration of the crosslinking agent in solution is 0.001-0.01 g / mL.

6. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that the photoinitiator... Including 2,2-diethoxyacetophenone, diphenylacetone, Darocur 1173, or Irgacure-184; the photoinitiator concentration in solution is 0.001-0.05 mg / mL.

7. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, Solvents include dioxane, N,N-dimethylformamide, or dimethyl sulfoxide.

8. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, Shear force is generated by two parallel but opposite forces; it is produced by squeezing the solution into a small-diameter pipe or by scraping the solution in one direction with a scraper.

9. The method for preparing the anisotropic hydrogel material as described in claim 2, characterized in that, In step (4), the concentration of the hydrobromic acid solution is 15-35 wt%, and the hydrolysis time is 4-8 hours.

10. The anisotropic hydrogel material of claim 1 and its application in embolic agents.

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