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Injectable hydrogel with self-healing and pH response properties, and preparation method and application thereof

A technology for injecting water and performance, which is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, organic active ingredients, etc. It can achieve the effect of excellent self-healing performance and obvious pH response performance.

Active Publication Date: 2017-05-31
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in recent years, injectable hydrogels based on chitosan and its derivatives have the following deficiencies: first, they are easily damaged due to external force extrusion, body fluid erosion, and other chemical substances, resulting in gel formation. Microscopic cracks are formed in the gel, and the propagation of these cracks will affect the integrity and mechanical properties of the gel structure, thereby shortening the life of the gel implant and endangering the health and safety of patients; Slight fluctuations, such as gastric juice is about 1-3, intestinal tissue is about 5-7, and the pH value of the occasional cancer tumor site is about below 6. These pH fluctuations will affect the water condensation used for drug release. Glue causes structural damage and destruction, which greatly affects the delivery of drugs; third, various organic chemical reagents are common in the common hydrogel preparation process, which limits its clinical application to a certain extent

Method used

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  • Injectable hydrogel with self-healing and pH response properties, and preparation method and application thereof
  • Injectable hydrogel with self-healing and pH response properties, and preparation method and application thereof
  • Injectable hydrogel with self-healing and pH response properties, and preparation method and application thereof

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preparation example Construction

[0043] A method for preparing a novel injectable hydrogel with self-healing and pH-responsive properties, comprising the following steps:

[0044] 1) Preparation of CEC (N-carboxyethyl chitosan) polymer: Add chitosan and acrylic acid to deionized water at a mass-volume ratio of 4g:(5-6)mL and react at 40-60°C to remove The amount of ionized water added is based on the ability to dissolve chitosan and acrylic acid. The ratio of chitosan to deionized water is 4g: (150-200) mL. After 65 hours, the CEC polymer is obtained, and the reaction is preferably 65-75 hours;

[0045] 2) Preparation of PEGDA (Dibenzaldehyde-Terminated Poly(ethyleneglycol), benzaldehyde-terminated polyethylene glycol) polymer: under nitrogen atmosphere, inert gas or vacuum environment, polyethylene glycol (PEG), p-formaldehyde Acylbenzoic acid and 4-dimethylaminopyridine are reacted in anhydrous tetrahydrofuran solvent, and N,N'-dicyclohexylcarboimide is added after 10-30 minutes. The total reaction time is ...

Embodiment 1

[0052] 1) Preparation of CEC (N-carboxyethyl chitosan) polymer: Add 5.84mL of acrylic acid to a round bottom flask filled with 200mL of deionized water, heat up to 50°C, and then add 4g of chitosan Sugar powder, stirred and reacted for 3 days, adjusted the pH to 9-10 with 1M NaOH aqueous solution to generate carboxylate; the reaction solution was dialyzed in deionized water for 2 days with a dialysis membrane with an average molecular weight of 8000 to remove excess salt, and the product was in - Freeze at 80°C, and use a freeze dryer to obtain a freeze-dried product after two to three days;

[0053] 2) Preparation of PEGDA (Dibenzaldehyde-Terminated Poly(ethyleneglycol), benzaldehyde-terminated polyethylene glycol) polymer: 4.89g of polyethylene glycol (PEG2000), 1.47g of p-formylbenzoic acid and 0.075g of 4-Dimethylaminopyridine was added to a 100mL round-bottomed flask, reacted at room temperature under nitrogen atmosphere for 20 minutes, then added 2.52g of N,N'-dicyclohex...

Embodiment 2

[0056] 1) Preparation of CEC (N-carboxyethyl chitosan) polymer: Add 5.84mL of acrylic acid to a round bottom flask filled with 200mL of deionized water, heat up to 50°C, and then add 4g of chitosan Sugar powder, stirred and reacted for 3 days, adjusted the pH to 9-10 with 1M NaOH aqueous solution to generate carboxylate; the reaction solution was dialyzed in deionized water for 2 days with a dialysis membrane with an average molecular weight of 8000 to remove excess salt, and the product was in - Freeze at 80°C, and use a freeze dryer to obtain a freeze-dried product after two to three days;

[0057] 2) Preparation of PEGDA (Dibenzaldehyde-Terminated Poly(ethyleneglycol), benzaldehyde-terminated polyethylene glycol) polymer: 4.89g of polyethylene glycol (PEG2000), 1.47g of p-formylbenzoic acid and 0.075g of 4-Dimethylaminopyridine was added to a 100mL round-bottomed flask, reacted at room temperature under nitrogen atmosphere for 20 minutes, then added 2.52g of N,N'-dicyclohex...

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Abstract

The invention relates to injectable hydrogel with self-healing and pH response properties, and a preparation method and an application thereof. The preparation method comprises the following steps: using a water soluble polymer CEC as a main raw material of the hydrogel; using a PEGDA polymer as a crosslinking agent; and mixing a CEC polymer solution with a PEGDA polymer solution, and performing mutual crosslinking to obtain the injectable hydrogel with self-healing and pH response properties. The preparation method is simple, no additional chemical reagent is added in the preparation process, no purification is carried out, the injectable hydrogel is safe and nontoxic, meanwhile the operation is convenient, and the raw material cost is low; and the prepared hydrogel CEC / PEGDA has excellent self-healing property, and obvious pH response property when serving as a drug carrier, can greatly promote the adhesion and proliferation of fibrocyte (L929), displays very strong biocompatibility, and has a very good application prospect in the field of drug transport.

Description

[0001] 【Technical field】 [0002] The invention belongs to the technical field of degradable biomedical materials, and in particular relates to a novel injectable hydrogel with self-healing and pH response properties and a preparation method thereof. [0003] 【Background technique】 [0004] In general chemotherapy, drugs are freely distributed throughout the body after being administered with conventional preparations, and only a small part can reach the lesion site. Drugs distributed in non-lesion sites not only cause certain side effects, but also greatly weaken the therapeutic effect. (Tacar O, Sriamornsak P, Dass CR. The Journal of pharmacy and pharmacology.2013; 65:157-70.) Therefore, it is of great importance to prepare a material that allows chemotherapy drugs to be injected in situ and released slowly at the lesion site. clinical significance. [0005] In recent years, based on its excellent pharmacokinetics and a variety of practical advantages, such as easy injection...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075A61K9/06A61K47/36A61K31/704A61P35/00C08L71/02C08L5/08
CPCA61K47/36A61K9/0019A61K9/06A61K31/704C08J3/075C08J3/246C08J2371/02C08J2405/08
Inventor 郭保林屈锦赵鑫
Owner XI AN JIAOTONG UNIV
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