CN114316306A - Preparation method of injectable temperature-sensitive hydrogel - Google Patents

Preparation method of injectable temperature-sensitive hydrogel Download PDF

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CN114316306A
CN114316306A CN202111649930.6A CN202111649930A CN114316306A CN 114316306 A CN114316306 A CN 114316306A CN 202111649930 A CN202111649930 A CN 202111649930A CN 114316306 A CN114316306 A CN 114316306A
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mixture
sensitive hydrogel
temperature
injectable
total mass
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刘平
孙淋暂
张乃保
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Puliyan Nanjing Medical Technology Co ltd
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Puliyan Nanjing Medical Technology Co ltd
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Abstract

The invention provides a preparation method of an injectable temperature-sensitive hydrogel, which comprises the following steps: mixing chitosan accounting for 1.2-3.6% of the total mass and hydroxypropyl methyl cellulose accounting for 7.5-9.8% of the total mass in a dry state to obtain a mixture I; slowly heating an acetic acid solution with the mass concentration of 0.53-1.54% from room temperature to 80-90 ℃ at the speed of 0.04 ℃/s-0.05 ℃/s to obtain a mixture II; adding the mixture I into the mixture II, and continuously stirring and dissolving for 30-50 min to obtain a mixture III; adding glycerol accounting for 30% -36% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel; the injectable temperature-sensitive hydrogel is preserved in an environment of 4-6 ℃. The preparation process is simple and controllable, and the obtained product has more excellent and stable performance.

Description

Preparation method of injectable temperature-sensitive hydrogel
Technical Field
The invention belongs to the technical field of polymer medical materials, and particularly relates to a preparation method of an injectable temperature-sensitive hydrogel.
Background
The temperature-sensitive hydrogel is an intelligent material, can perform sol-gel conversion under the change of temperature, can perform the repair and treatment of specific parts, and has wide application prospect in the field of biomedicine. Temperature sensitive gels mainly comprise three major types, namely isopropyl acrylamide copolymers, block polymers and polysaccharide/salt systems.
In view of the current state of research, the most promising system is the polysaccharide/salt system, which has good biological applicability but still has some problems, limiting its application. There are mainly the following problems:
the hydrophilicity of macromolecules is insufficient, the concentration of a macromolecule solution is low, and therefore the strength of a formed gel framework is low, the water content is high, and water is easy to run off;
secondly, the sol-gel phase change rate needs to be further improved;
thirdly, the degradation and erosion rate can not meet the long-term stable drug release requirement. Therefore, the selection of the temperature-sensitive material is very important.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: the preparation method of the injectable temperature-sensitive hydrogel is provided, the preparation process is simple and controllable, and the performance of the obtained product is more excellent and stable.
The invention is realized by the following steps: a preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan accounting for 1.2-3.6% of the total mass and hydroxypropyl methyl cellulose accounting for 7.5-9.8% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 0.53-1.54% from room temperature to 80-90 ℃ at the speed of 0.04 ℃/s-0.05 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 30-50 min to obtain a mixture III;
adding glycerol accounting for 30% -36% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 4-6 ℃.
Further, the method comprises the following steps:
mixing chitosan accounting for 1.2 percent of the total mass and hydroxypropyl methyl cellulose accounting for 7.5 percent of the total mass under a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 0.53% from room temperature to 80 ℃ at the speed of 0.04 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 30min to obtain a mixture III;
adding glycerol accounting for 30% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 4 ℃.
Further, the method comprises the following steps:
mixing chitosan accounting for 3.6% of the total mass and hydroxypropyl methyl cellulose accounting for 9.8% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 1.54% from room temperature to 90 ℃ at the speed of 0.05 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 50min to obtain a mixture III;
adding glycerol accounting for 36% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 6 ℃.
Further, the method comprises the following steps:
mixing chitosan accounting for 2.6% of the total mass and hydroxypropyl methyl cellulose accounting for 8.4% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 1.2% from room temperature to 85 ℃ at the speed of 0.042 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 40min to obtain a mixture III;
adding glycerol accounting for 32.5 percent of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 5 ℃.
Further, the viscosity of the hydroxypropyl methylcellulose is 6-8 mPa.s.
And further adding the mixture I into the mixture II, and then putting the mixture I into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 30min-50min to obtain a mixture III.
And further, the glycerol is added into the second mixture in a dropwise adding mode, and the injectable temperature-sensitive hydrogel is obtained after uniform mixing.
Further, the heating process of the acetic acid solution is completed by slowly heating in a water bath or oil bath environment.
The invention also provides an injectable temperature-sensitive hydrogel prepared by the preparation method.
The invention also provides application of the injectable temperature-sensitive hydrogel, and the injectable temperature-sensitive hydrogel is used for manufacturing a prosthesis.
The invention has the following beneficial effects: the temperature-sensitive hydrogel has better hemostatic property, antibacterial property, moisture retention, healing promotion and formability by adding chitosan; the thermo-sensitive cellulose ether-hydroxypropyl methylcellulose and chitosan both belong to polysaccharide substances, and the structures of the cellulose ether-hydroxypropyl methylcellulose and chitosan have certain similarity, so that the compatibility among the substances can be enhanced; in addition, the addition of the cellulose ether can improve the concentration of the polymer in the system, reduce the loss of water and simultaneously enhance the strength of a gel skeleton; the hydroxypropyl methyl cellulose has good chemical stability and biodegradability, and the hydrogel preparation cost is low.
Detailed Description
The invention is further described below. The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby.
Example one
A preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan accounting for 1.2 percent of the total mass and hydroxypropyl methyl cellulose accounting for 7.5 percent of the total mass under a dry state to obtain a mixture I, wherein the viscosity of the hydroxypropyl methyl cellulose is 6 mPa.s.
The acetic acid solution with the mass concentration of 0.53% was put into a water bath tank and slowly heated from room temperature to 80 ℃ at a rate of 0.04 ℃/s to obtain a second mixture.
And adding the mixture I into the mixture II, and putting the mixture I into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 30min to obtain a mixture III.
Dropwise adding glycerol accounting for 30% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 4 ℃.
The embodiment also provides an injectable temperature-sensitive hydrogel prepared by the preparation method.
The embodiment also provides application of the injectable temperature-sensitive hydrogel, and the injectable temperature-sensitive hydrogel is used for manufacturing a prosthesis.
Example two
A preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan 3.6% of the total mass and hydroxypropyl methylcellulose 9.8% of the total mass under dry state to obtain a mixture I, wherein the viscosity of the hydroxypropyl methylcellulose is 7 mPa.s.
The acetic acid solution having a mass concentration of 1.54% was put into an oil bath tank and slowly heated from room temperature to 90 ℃ at a rate of 0.05 ℃/s to obtain a second mixture.
And adding the mixture I into the mixture II, and then putting the mixture I into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 50min to obtain a mixture III.
And dropwise adding glycerol accounting for 36% of the total mass into the second mixture and uniformly mixing to obtain the injectable temperature-sensitive hydrogel.
The injectable temperature-sensitive hydrogel is preserved in an environment of 6 ℃.
The embodiment also provides an injectable temperature-sensitive hydrogel prepared by the preparation method.
The embodiment also provides application of the injectable temperature-sensitive hydrogel, and the injectable temperature-sensitive hydrogel is used for manufacturing a prosthesis.
EXAMPLE III
A preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan 2.6% of the total mass and hydroxypropyl methylcellulose 8.4% of the total mass under dry state to obtain a mixture I, wherein the viscosity of the hydroxypropyl methylcellulose is 8 mPa.s.
The acetic acid solution with a mass concentration of 1.2% was put into a water bath tank and slowly heated from room temperature to 85 ℃ at a rate of 0.042 ℃/s to obtain a second mixture.
And adding the mixture I into the mixture II, and putting the mixture I into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 40min to obtain a mixture III.
And dropwise adding glycerol accounting for 32.5 percent of the total mass into the second mixture and uniformly mixing to obtain the injectable temperature-sensitive hydrogel.
The injectable temperature-sensitive hydrogel is preserved in an environment of 5 ℃.
Example four
A preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan accounting for 1.8% of the total mass and hydroxypropyl methyl cellulose accounting for 9.1% of the total mass in a dry state to obtain a mixture I, wherein the viscosity of the hydroxypropyl methyl cellulose is 7 mPa.s.
The acetic acid solution with the mass concentration of 0.8% was put into a heating thermostat and slowly heated from room temperature to 82 ℃ at a rate of 0.046 ℃/s to obtain a second mixture.
And adding the mixture I into the mixture II, and putting the mixture into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 35min to obtain a mixture III.
And dropwise adding glycerol accounting for 34.5% of the total mass into the second mixture and uniformly mixing to obtain the injectable temperature-sensitive hydrogel.
The injectable temperature-sensitive hydrogel is preserved in an environment of 5 ℃.
EXAMPLE five
A preparation method of an injectable temperature-sensitive hydrogel comprises the following steps:
mixing chitosan 3.2% of the total mass and hydroxypropyl methylcellulose 7.9% of the total mass under dry state to obtain a mixture I, wherein the viscosity of the hydroxypropyl methylcellulose is 8 mPa.s.
The acetic acid solution with the mass concentration of 1.05% was put into a water bath tank and slowly heated from room temperature to 90 ℃ at a rate of 0.042 ℃/s to obtain a second mixture.
And adding the mixture I into the mixture II, and then putting the mixture I into a constant-temperature magnetic stirrer to be continuously stirred and dissolved for 45min to obtain a mixture III.
And dropwise adding the glycerol accounting for 31.8 percent of the total mass into the second mixture dropwise, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel.
The injectable temperature-sensitive hydrogel is preserved in an environment of 4 ℃.
In the invention, the acetic acid solution is slowly heated by adopting a water bath tank, an oil bath tank and a constant temperature heating tank, so that an exogenous heating substance can be prevented from being introduced, and the temperature of 25 +/-0.5 ℃ can be considered as room temperature.
Figure DEST_PATH_IMAGE001
And (4) conclusion: according to the comparison of galactomannan-poly (N-isopropylacrylamide) composite hydrogel, the invention has the advantages of proper Young modulus, stable phase transition temperature and stable phase transition time, meets the biological evaluation of cytotoxicity, and is stable and not easy to deteriorate and degrade under the required storage environment.
The above is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.

Claims (10)

1. The preparation method of the injectable temperature-sensitive hydrogel is characterized by comprising the following steps:
mixing chitosan accounting for 1.2-3.6% of the total mass and hydroxypropyl methyl cellulose accounting for 7.5-9.8% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 0.53-1.54% from room temperature to 80-90 ℃ at the speed of 0.04 ℃/s-0.05 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 30-50 min to obtain a mixture III;
adding glycerol accounting for 30% -36% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 4-6 ℃.
2. The method for preparing the injectable temperature-sensitive hydrogel according to claim 1, comprising the following steps:
mixing chitosan accounting for 1.2 percent of the total mass and hydroxypropyl methyl cellulose accounting for 7.5 percent of the total mass under a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 0.53% from room temperature to 80 ℃ at the speed of 0.04 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 30min to obtain a mixture III;
adding glycerol accounting for 30% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 4 ℃.
3. The method for preparing the injectable temperature-sensitive hydrogel according to claim 1, comprising the following steps:
mixing chitosan accounting for 3.6% of the total mass and hydroxypropyl methyl cellulose accounting for 9.8% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 1.54% from room temperature to 90 ℃ at the speed of 0.05 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 50min to obtain a mixture III;
adding glycerol accounting for 36% of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 6 ℃.
4. The method for preparing the injectable temperature-sensitive hydrogel according to claim 1, comprising the following steps:
mixing chitosan accounting for 2.6% of the total mass and hydroxypropyl methyl cellulose accounting for 8.4% of the total mass in a dry state to obtain a mixture I;
slowly heating an acetic acid solution with the mass concentration of 1.2% from room temperature to 85 ℃ at the speed of 0.042 ℃/s to obtain a mixture II;
adding the mixture I into the mixture II, and continuously stirring and dissolving for 40min to obtain a mixture III;
adding glycerol accounting for 32.5 percent of the total mass into the second mixture, and uniformly mixing to obtain the injectable temperature-sensitive hydrogel;
the injectable temperature-sensitive hydrogel is preserved in an environment of 5 ℃.
5. The method for preparing an injectable temperature-sensitive hydrogel according to any one of claims 1 to 4, wherein the viscosity of the hydroxypropylmethylcellulose is 6 to 8 mPa.s.
6. The preparation method of the injectable temperature-sensitive hydrogel according to any one of claims 1 to 4, wherein the mixture I is added into the mixture II, and then the mixture II is placed into a constant temperature magnetic stirrer to be continuously stirred and dissolved for 30min to 50min to obtain a mixture III.
7. The preparation method of the injectable temperature-sensitive hydrogel according to any one of claims 1 to 4, wherein the glycerol is added into the second mixture in a dropwise manner, and the injectable temperature-sensitive hydrogel is obtained by uniformly mixing.
8. The preparation method of the injectable temperature-sensitive hydrogel according to any one of claims 1 to 4, wherein the heating process of the acetic acid solution is completed by slow heating in a water bath or oil bath environment.
9. An injectable temperature-sensitive hydrogel, characterized in that it is prepared by the preparation method of claim 1.
10. The application of the injectable temperature-sensitive hydrogel is characterized in that the injectable temperature-sensitive hydrogel is used for manufacturing a prosthesis.
CN202111649930.6A 2021-12-30 2021-12-30 Preparation method of injectable temperature-sensitive hydrogel Pending CN114316306A (en)

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Application publication date: 20220412