Crosslinking sodium hyaluronate gel and preparation method thereof

A technology for cross-linking hyaluronic acid and sodium hyaluronate, which is used in pharmaceutical formulations, prostheses, drug delivery, etc., can solve the problem of inability to effectively increase the proportion of cross-linking modification, and achieves reducing the degree of suspension modification and improving cross-linking. The effect of joint modification and low cost

Active Publication Date: 2017-01-04
BEIJING DATSING BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The above methods adjust tissue toxicity and degradation time by controlling the total degree of modification, all of which belong to the category of traditional cross-linking technology, and cannot effectively increase the proportion of the degree of cross-linking modification in the total degree of cross-linking

Method used

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  • Crosslinking sodium hyaluronate gel and preparation method thereof
  • Crosslinking sodium hyaluronate gel and preparation method thereof
  • Crosslinking sodium hyaluronate gel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The influence of time on degree of cross-linking in embodiment 1 traditional cross-linking process

[0043] 1. Add 1.0 g of sodium hyaluronate with a molecular weight of 2 million Daltons into 150 mL of 1% (w / w) NaOH solution, and stir at room temperature for 4 hours until completely dissolved.

[0044] 2. Take 0.2mL of 1,4-butanediol diglycidyl ether, dilute it with 50mL of distilled water and keep it for later use.

[0045] 3. Put the NaOH solution of sodium hyaluronate in a magnetic stirrer, add the diluted BDDE solution dropwise to the system under stirring at room temperature, and finish dropping in 10 minutes. After dropping, continue to react for a certain period of time. The reaction time is shown in the table 1.

[0046] 4. Add 0.005 mol / L hydrochloric acid solution to adjust to pH = 7.2, and balance for 2 hours under stirring, then add 500 mL of absolute ethanol, precipitate for 2 hours, and take out the massive solid.

[0047] After freeze-drying the obtain...

Embodiment 2

[0050] Influence of crosslinking temperature on degree of crosslinking in the traditional crosslinking process of embodiment 2

[0051] 1. Add 1.0 g of sodium hyaluronate with a molecular weight of 2 million Daltons into 150 mL of 1% (w / w) NaOH solution, and stir at room temperature for 4 hours until completely dissolved.

[0052] 2. Take 0.2mL of 1,4-butanediol diglycidyl ether, dilute it with 50mL of distilled water and keep it for later use.

[0053] 3. Put the NaOH solution of sodium hyaluronate in a magnetic stirrer, and add the BDDE solution dropwise to the system under stirring in the temperature range of 25-45°C. After 10 minutes, continue to react for 36 hours. .

[0054] 4. Add 0.005 mol / L hydrochloric acid solution to adjust to pH = 7.2, and balance for 2 hours under stirring, then add 500 mL of absolute ethanol, precipitate for 2 hours, and take out the massive solid.

[0055] After freeze-drying the obtained solid, the degree of cross-linking was tested, and the...

Embodiment 3

[0058] Influence of reaction time on degree of crosslinking in the ultrasonic crosslinking process of embodiment 3

[0059] 1. Add 1.0 g of sodium hyaluronate with a molecular weight of 2 million Daltons into 150 mL of 1% (w / w) NaOH solution, and stir at room temperature for 4 hours until completely dissolved.

[0060] 2. Take 0.2mL of 1,4-butanediol diglycidyl ether, dilute it with 50mL of distilled water and keep it for later use.

[0061] 3. Put the NaOH solution of sodium hyaluronate in an ultrasonic reactor with adjustable frequency, adjust the ultrasonic frequency to 25KHz, ultrasonicate at room temperature, and add the BDDE solution to the system dropwise, and finish dropping in 10 minutes. After dropping, continue to ultrasonicate React for 0 to 40 minutes, and observe the effect of reaction time on the degree of crosslinking (Table 3).

[0062] 4. Add 0.005 mol / L hydrochloric acid solution to adjust to pH = 7.2, and balance for 2 hours under stirring, then add 500 mL...

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Abstract

The invention provides crosslinking sodium hyaluronate gel and a preparation method thereof. The preparation method comprises the following steps: dropwise adding a crosslinking agent in an aqueous alkaline solution of sodium hyaluronate and carrying out crosslinking reaction; after reaction is finished, adjusting pH value of a system to be 7.1-7.5 with acid; stirring for 1-2 hours; and then precipitating with anhydrous ethanol to obtain the crosslinking sodium hyaluronate gel. The shortcoming that the proportion of crosslinking modification degree in a traditional crosslinking technology is lower (about 10%) is overcome effectively, and the proportion of the crosslinking modification degree is increased to be about 60% and is controllable. An ultrasonic crosslinking technology is introduced, the proportion of the crosslinking modification degree in crosslinking hyaluronic acid can be increased effectively, the proportion of suspension modification degree is reduced, and degradation time of a material is prolonged.

Description

technical field [0001] The invention relates to the technical field of material engineering, in particular to a cross-linked sodium hyaluronate gel and a preparation method thereof. Background technique [0002] Hyaluronic acid (Hyaluronic acid, HA), also known as hyaluronic acid, is the most representative of mucopolysaccharides. It is widely distributed in various parts of the human body. It shows a variety of important functions in the body with its unique molecular structure and physical and chemical properties. Physiological functions, such as lubricating joints, regulating the permeability of blood vessel walls, regulating protein, water and electrolyte diffusion and operation, promoting wound healing, etc. In addition, hyaluronic acid has a special water-locking effect and is the most moisturizing substance found in nature so far. It is called an ideal natural moisturizing factor (Natural moisturizing factor, NMF), such as 2% pure hyaluronic acid aqueous solution Can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/28C08J3/075A61L27/52A61L27/50A61L27/20C08L5/08
CPCA61L27/20A61L27/50A61L27/52A61L2400/06C08J3/075C08J3/24C08J3/28C08J2305/08C08L5/08
Inventor 孙乐青袁源张婷婷李湘杰李次会
Owner BEIJING DATSING BIO TECH
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