Chitosan hydrogel and preparation method thereof

Abstract

The chitosan hydrogel disclosed by the invention is prepared from the following components in parts by weight: 6 to 15 parts of carboxymethyl chitosan, 0.4 to 1 part of a cross-linking agent and 300 to 900 parts of water. The invention belongs to the technical field of polymer hydrogel, and particularly relates to chitosan hydrogel and a preparation method thereof, the prepared chitosan hydrogel is low in toxicity and safer, a low-temperature and high-temperature step-by-step cross-linking product is adopted, compared with a one-step cross-linking product, the residual amount of a cross-linking agent is lower, a chitosan solution and the cross-linking agent react slowly under the low-temperature condition, and the cross-linking effect is good. The mixing is more sufficient under a liquid condition.

Description

Technical Field

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

[0002] Hydrogel is a kind of composite system with a three-dimensional network structure formed by cross-linking hydrophilic polymer compounds by physical or chemical methods and containing a large amount of water. It has physical and chemical properties very similar to human tissues, such as high water content and good biocompatibility. Therefore, it is widely used in biomedical fields such as drug controlled release and tissue repair. Among them, injectable hydrogels are particularly eye-catching. Injectable hydrogel materials generally have a certain fluidity in vitro and can be evenly mixed with cells, drugs or active molecules. When injected into the body, they can gel in situ to form hydrogels. The cells embedded inside can continue to grow, and drugs or active molecules can also be gradually released, thereby playing a role in tissue repair or disease treatment. According to the different gelation or cross-linking methods, injectable hydrogels can be divided into two categories: chemically cross-linked hydrogels and physically cross-linked hydrogels. Chemically cross-linked hydrogels are formed by chemical cross-linking and have good mechanical properties and stability, but generally require the addition of cross-linking agents or initiators, which may produce greater toxicity; while physically cross-linked hydrogels are formed by hydrogen bonds, hydrophobic interactions, etc., and cause less damage to cells, but their performance is easily changed with changes in external physical conditions and their stability is poor.

[0003] Chitosan is a cationic natural high molecular weight polysaccharide obtained by deacetylation of chitin. Since its discovery in 1859, chitosan has attracted much attention from researchers. Due to its abundant sources, low price, good degradability and film-forming properties, chitosan has been widely used in chemical and chemical fields such as water treatment and food preservation. Through in-depth research, it was found that chitosan also has good physical and chemical properties such as biocompatibility, antibacterial and hemostatic activity, and contains a large number of active groups such as hydroxyl, amino and acetylated amino groups that are easy to modify on the molecular chain. Therefore, chitosan has also attracted much attention in the field of biomedicine. Among them, injectable chitosan hydrogel has aroused great interest among researchers in recent years. Because it retains the excellent properties of chitosan and has the advantages of injectable hydrogel, injectable chitosan hydrogel has gradually attracted attention in biomedical fields such as drug carriers, gene carriers, cell scaffolds and wound repair.

[0004] Therefore, the primary purpose of the present invention is to provide a method for preparing chitosan hydrogel. The hydrogel prepared by this method is safer and has better thermal stability than conventional glutaraldehyde cross-linking. Compared with directly adding the cross-linking agent to the reaction material, the diluted cross-linking agent can be fully mixed with the material, and the product has better uniformity in viscoelasticity, light transmittance, etc. The product using low-temperature and then high-temperature step-by-step cross-linking has lower cross-linking agent residue than the one-step cross-linking product. Finally, a certain amount of non-cross-linked chitosan solution is added, and the product has better viscoelasticity. At the same time, the non-cross-linked chitosan can reduce the irritation of the product to the skin and increase the immune buffer period. Summary of the invention

[0005] In order to solve the deficiencies of the prior art, the primary purpose of the present invention is to provide a chitosan hydrogel, a preparation method, and evaluate its performance and heat-resistant modification effect. The present invention selects a less toxic and safer BDDE crosslinking agent, and the crosslinking product is first crosslinked at low temperature and then at high temperature. The crosslinking agent residue is lower than that of the one-step crosslinking product. Under low temperature conditions, the chitosan solution and the crosslinking agent react slowly, and the mixing is more complete under liquid conditions. Finally, a certain amount of non-crosslinked chitosan solution is added, and the product has better viscoelasticity. At the same time, the non-crosslinked chitosan can reduce the irritation of the product to the skin and increase the immune buffer period.

[0006] The technical scheme adopted by the present invention is as follows: a chitosan hydrogel of the present invention comprises the following components in parts by weight: 6-15 parts of carboxymethyl chitosan, 0.4-1 part of a cross-linking agent, and 300-900 parts of water.

[0007] Furthermore, the chitosan hydrogel of the present invention comprises the following components in parts by weight: 8-12 parts of carboxymethyl chitosan, 0.5-0.7 parts of a cross-linking agent, and 450-700 parts of water.

[0008] Furthermore, the chitosan hydrogel of the present invention comprises the following components in parts by weight: 9 parts of carboxymethyl chitosan, 0.6 parts of a cross-linking agent, and 490 parts of water.

[0009] A method for preparing chitosan hydrogel comprises the following steps:

[0010] Step 1: weigh 9 g of carboxymethyl chitosan, add water to 450 g, and stir to dissolve to obtain a chitosan solution;

[0011] Step 2: Weigh 0.6 mL of the cross-linking agent, add water to 50 mL, and stir to dissolve to obtain a cross-linking agent solution;

[0012] Step 3: Weigh 100 g of chitosan solution, place it in a beaker, stir, then add 50 mL of cross-linker solution, mix thoroughly, add to a water bath, and cross-link in a water bath for 2 h;

[0013] Step 4: Add 50 g of chitosan solution to the cross-linked solution in step 3, and cross-link in a water bath for 2 h to obtain cross-linked chitosan;

[0014] Step 5: Place the cross-linked chitosan in a dialysis bag and dialyze for 72 hours;

[0015] Step 6: After the dialysis is completed, add 50 g of chitosan solution and mix thoroughly to obtain chitosan gel;

[0016] Step 7: Canning and sterilizing to obtain the chitosan hydrogel finished product.

[0017] Furthermore, the viscosity of the carboxymethyl chitosan in step 1 is 150 and the molecular weight is 200,000.

[0018] Furthermore, the cross-linking agent in step 2 is BEED.

[0019] Furthermore, in step three, the water bath temperature is 35°C.

[0020] Furthermore, in step 4, the water bath temperature is 45°C.

[0021] Furthermore, in step 5, the molecular weight cutoff of the dialysis bag is 50,000 Da, and the water is replaced every 8 hours during the dialysis process.

[0022] After adopting the above technical solution, the beneficial effects of the present invention are as follows:

[0023] 1. The gel obtained by cross-linking with BDDE has better thermal stability, and does not change color or decompose at 121°C for 30 minutes;

[0024] 2. Compared with conventional glutaraldehyde as a cross-linking agent, BDDE is safer;

[0025] 3. Compared with directly adding the cross-linking agent to the reaction material, the diluted cross-linking agent can be fully mixed with the material, and the uniformity of the product's viscoelasticity, light transmittance, etc. is better;

[0026] 4. The cross-linking product is cross-linked step by step at low temperature and then at high temperature. Compared with the one-step cross-linking product, the cross-linking agent residue is lower;

[0027] 5. Finally, add a certain amount of non-cross-linked chitosan solution to make the product more viscoelastic. At the same time, non-cross-linked chitosan can reduce the irritation of the product to the skin and increase the immune buffer period. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a physical picture of chitosan hydrogel. DETAILED DESCRIPTION

[0029] The technical solutions in the embodiments of the present invention are clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0030] The overall technical solution of the present invention is first described below.

[0031] The invention discloses a chitosan hydrogel, which comprises the following components in parts by weight: 6-15 parts of carboxymethyl chitosan, 0.4-1 part of a cross-linking agent and 300-900 parts of water.

[0032] When the above substances are used to prepare chitosan hydrogel, the following preparation steps are included:

[0033] Step 1: weigh 9 g of carboxymethyl chitosan, add water to 450 g, and stir to dissolve to obtain a chitosan solution;

[0034] Step 2: Weigh 0.6 mL of the cross-linking agent, add water to 50 mL, and stir to dissolve to obtain a cross-linking agent solution;

[0035] Step 3: Weigh 100 g of chitosan solution, place it in a beaker, stir, then add 50 mL of cross-linker solution, mix thoroughly, add to a water bath, and cross-link in a water bath for 2 h;

[0036] Step 4: Add 50 g of chitosan solution to the cross-linked solution in step 3, and cross-link in a water bath for 2 h to obtain cross-linked chitosan;

[0037] Step 5: Place the cross-linked chitosan in a dialysis bag and dialyze for 72 hours;

[0038] Step 6: After the dialysis is completed, add 50 g of chitosan solution and mix thoroughly to obtain chitosan gel;

[0039] Step 7: Canning and sterilizing to obtain the chitosan hydrogel finished product.

[0040] Next, the present invention is described in detail through specific embodiments.

[0041] Example 1

[0042] Weigh 6 g of carboxymethyl chitosan (150 viscosity, molecular weight 200,000), add water to 300 g, dissolve to obtain A, weigh 0.6 mL of BDDE (99%), add water to 34 mL, obtain B, weigh 68 g of chitosan solution (A), put it into a beaker, stir, and add 34 mL of cross-linking agent (B), mix thoroughly and put it into a 35°C water bath, cross-link in a water bath for 2 hours, add 68 g of chitosan solution (A) again, cross-link in a water bath (45°C) for 2 hours to obtain cross-linked chitosan; put the cross-linked chitosan into a dialysis bag and dialyze it for 72 hours (the dialysis bag has a molecular weight cutoff of 50,000 Da, and the water is replaced every 8 hours during the dialysis process). After the dialysis is completed, add 68 g of chitosan solution (A) and mix thoroughly to obtain chitosan gel, and sterilize the chitosan hydrogel product in a can.

[0043] Example 2

[0044] Weigh 9 g of carboxymethyl chitosan (150 viscosity, molecular weight 200,000), add water to 450 g, dissolve to obtain A, weigh 0.6 mL of BDDE (99%), add water to 50 mL, obtain B, weigh 100 g of chitosan solution (A), put it into a beaker, stir, add 50 mL of cross-linking agent (B), mix thoroughly and put it into a 35°C water bath, cross-link in a water bath for 2 hours, add 50 g of chitosan solution (A) again, cross-link in a water bath (45°C) for 2 hours to obtain cross-linked chitosan; put the cross-linked chitosan into a dialysis bag and dialyze it for 72 hours (the dialysis bag has a molecular weight cutoff of 50,000 Da, and the water is replaced every 8 hours during the dialysis process). After the dialysis is completed, add 50 g of chitosan solution (A) and mix thoroughly to obtain chitosan gel, and sterilize the chitosan hydrogel product in a can.

[0045] Example 3

[0046] Weigh 15 g of carboxymethyl chitosan (150 viscosity, molecular weight 200,000), add water to 750 g, dissolve to obtain A, weigh 1 mL of BDDE (99%), add water to 84 mL to obtain B, weigh 168 g of chitosan solution (A), put it into a beaker, stir, and add 84 mL of cross-linking agent (B), mix thoroughly and put it into a 35°C water bath, cross-link in a water bath for 2 hours, add 168 g of chitosan solution (A) again, cross-link in a water bath (45°C) for 2 hours to obtain cross-linked chitosan; put the cross-linked chitosan into a dialysis bag and dialyze it for 72 hours (the dialysis bag has a molecular weight cutoff of 50,000 Da, and the water is replaced every 8 hours during the dialysis process). After the dialysis is completed, add 168 g of chitosan solution (A) and mix thoroughly to obtain chitosan gel, and sterilize the chitosan hydrogel product in a can.

[0047] The chitosan hydrogel products of the above examples were baked at 121 degrees for 30 minutes without changing color or decomposition.

[0048] The present invention and its embodiments are described above, but such description is not restrictive. What is shown in the specification is only part of the embodiments of the present invention, and the actual method is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. A chitosan hydrogel, characterized in that: The invention comprises the following components in parts by weight: 6-15 parts of carboxymethyl chitosan, 0.4-1 part of a cross-linking agent and 300-900 parts of water.

2. A chitosan hydrogel according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 8-12 parts of carboxymethyl chitosan, 0.5-0.7 parts of a cross-linking agent and 450-700 parts of water.

3. A chitosan hydrogel according to claim 1-2, characterized in that: The invention comprises the following components in parts by weight: 9 parts of carboxymethyl chitosan, 0.6 parts of a cross-linking agent and 490 parts of water.

4. A method for preparing the chitosan hydrogel according to any one of claims 1 to 4, characterized in that: The following steps are involved: Step 1: weigh 9 g of carboxymethyl chitosan, add water to 450 g, and stir to dissolve to obtain a chitosan solution; Step 2: Weigh 0.6 mL of the cross-linking agent, add water to 50 mL, and stir to dissolve to obtain a cross-linking agent solution; Step 3: Weigh 100 g of chitosan solution, place it in a beaker, stir, then add 50 mL of cross-linker solution, mix thoroughly, add to a water bath, and cross-link in a water bath for 2 h; Step 4: Add 50 g of chitosan solution to the cross-linked solution in step 3, and cross-link in a water bath for 2 h to obtain cross-linked chitosan; Step 5: Place the cross-linked chitosan in a dialysis bag and dialyze for 72 hours; Step 6: After the dialysis is completed, add 50 g of chitosan solution and mix thoroughly to obtain chitosan gel; Step 7: Canning and sterilizing to obtain the chitosan hydrogel finished product.

5. The preparation method according to claim 4, characterized in that: Step 1: The viscosity of carboxymethyl chitosan is 150 and the molecular weight is 200,000.

6. The preparation method according to claim 4, characterized in that: The cross-linking agent in step 2 is BEED.

7. The preparation method according to claim 4, characterized in that: In step 3, the water bath temperature is 35°C.

8. The preparation method according to claim 4, characterized in that: Step 4 In step 4, the water bath temperature is 45°C.

9. The preparation method according to claim 4, characterized in that: In step 5, the molecular weight cutoff of the dialysis bag is 50,000 Da, and the water is replaced every 8 hours during the dialysis process.

Images