A kind of preparation method of carboxymethyl chitin critical hydrogel

Abstract

The invention provides a preparation method of a completely new gel form, namely a critical gel, wherein with carboxymethyl chitin as a raw material and natural and non-toxic amino acid, namely lysine, as a modifying substance, the critical gel is prepared under the catalytic action of a coupling reagent, namely 4-(4,6-dimethoxytriazin-2-yl)-4-methyl morpholine hydrochloride (DMTMM). The gel has the main characteristic that the gel can constantly keep viscous modulus and elasticity modulus equal, which is to say the gel possesses two properties, namely high viscosity and high elasticity. The modified gel, which is under a 'critical state', can achieve terminal sterilization, prolong an in vivo residue time and achieve single-dose injection; with the application of the non-toxic amino acid modifying substance, the intrinsic biocompatibility and bio-activity of the carboxymethyl chitin are reserved, and all potential risks are avoided; since the viscous modulus and the elasticity modulus are simultaneously increased and are constantly kept equal, the viscoelasticity of the carboxymethyl chitin is enhanced; and meanwhile, the original liquid state of the carboxymethyl chitin is kept, so that pain in injection can be relieved easily.

Description

technical field

[0001] The invention relates to the technical field of medical biomaterials, in particular to a method for preparing an injectable, water-soluble, viscous and elastic carboxymethyl chitin critical state hydrogel, and the critical state hydrogel is both viscous And elasticity, it has potential application value in joint cavity injection, ophthalmic viscoelastic agent and so on. technical background

[0002] Osteoarthritis (OA) is one of the most common joint diseases affecting human health. disease. Its incidence rate is about 5% or more, and it is one of the main diseases that cause functional disability of people over 50 years old, cause economic losses and affect social development. Years of research have found that osteoarthritis is related to factors such as trauma, inflammation, aging, metabolism and immunity. Overall, the main pathological features of OA are apoptosis of articular chondrocytes and progressive degradation of extracellular matrix. The...

Examples

Embodiment 1

[0027] Dissolve 2g of carboxymethyl chitin dry powder (molecular weight: 580,000 Daltons, degree of deacetylation: 13.41%) in 50mL of water for injection, stir well, then add 0.5g of lysine and 1g of 4-(4,6- Dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH of the reaction solution was adjusted to 6.0 with 1M HCl, and reacted at 37° C. for 24 hours.

[0028] Homogenize the reaction mixture, slowly add 2 times the volume of ethanol dropwise under stirring, wash the dry powder twice with ethanol, and dry it in vacuum for 2 hours, then dissolve it in 100mL of water for injection. Stir well and adjust the pH to 7.2 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

Embodiment 2

[0030] Dissolve 1.5g of carboxymethyl chitin dry powder (molecular weight: 650,000 Daltons, degree of deacetylation: 9.95%) in 60mL of water for injection, stir well, then add 0.8g of lysine and 2.5g of 4-(4, 6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH of the reaction solution was adjusted to 7.5 with 1M HCl, and reacted at 25° C. for 48 hours.

[0031] The mixture obtained by the reaction was homogenized, and slowly added dropwise 2 times the volume of ethanol in the mixture under stirring, and the dry powder was washed with ethanol twice, dried in vacuum for 4 hours, and then dissolved in 90 mL of water for injection. Stir well and adjust the pH value to 6.5 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

Embodiment 3

[0033] Dissolve 5 g of carboxymethyl chitin dry powder (molecular weight: 840,000 Daltons, degree of deacetylation: 7.99%) in 75 mL of water for injection, stir well, then add 1.5 g of lysine and 0.25 g of 4-(4,6 -dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH value of the reaction solution was adjusted to 7.2 with 1M HCl, and placed at 4° C. for 240 h.

[0034] The mixture obtained by the reaction was homogenized, and slowly added dropwise 3 times the volume of ethanol of the mixture under stirring, the dry powder was washed with ethanol 5 times, dried in vacuum for 30min, and then dissolved in 200mL of water for injection. Stir thoroughly and evenly, and adjust the pH value to 7.0 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

technical field

[0001] The invention relates to the technical field of medical biomaterials, in particular to a method for preparing an injectable, water-soluble, viscous and elastic carboxymethyl chitin critical state hydrogel, and the critical state hydrogel is both viscous And elasticity, it has potential application value in joint cavity injection, ophthalmic viscoelastic agent and so on. technical background

[0002] Osteoarthritis (OA) is one of the most common joint diseases affecting human health. disease. Its incidence rate is about 5% or more, and it is one of the main diseases that cause functional disability of people over 50 years old, cause economic losses and affect social development. Years of research have found that osteoarthritis is related to factors such as trauma, inflammation, aging, metabolism and immunity. Overall, the main pathological features of OA are apoptosis of articular chondrocytes and progressive degradation of extracellular matrix. The...

Examples

Embodiment 1

[0027] Dissolve 2g of carboxymethyl chitin dry powder (molecular weight: 580,000 Daltons, degree of deacetylation: 13.41%) in 50mL of water for injection, stir well, then add 0.5g of lysine and 1g of 4-(4,6- Dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH of the reaction solution was adjusted to 6.0 with 1M HCl, and reacted at 37° C. for 24 hours.

[0028] Homogenize the reaction mixture, slowly add 2 times the volume of ethanol dropwise under stirring, wash the dry powder twice with ethanol, and dry it in vacuum for 2 hours, then dissolve it in 100mL of water for injection. Stir well and adjust the pH to 7.2 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

Embodiment 2

[0030] Dissolve 1.5g of carboxymethyl chitin dry powder (molecular weight: 650,000 Daltons, degree of deacetylation: 9.95%) in 60mL of water for injection, stir well, then add 0.8g of lysine and 2.5g of 4-(4, 6-dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH of the reaction solution was adjusted to 7.5 with 1M HCl, and reacted at 25° C. for 48 hours.

[0031] The mixture obtained by the reaction was homogenized, and slowly added dropwise 2 times the volume of ethanol in the mixture under stirring, and the dry powder was washed with ethanol twice, dried in vacuum for 4 hours, and then dissolved in 90 mL of water for injection. Stir well and adjust the pH value to 6.5 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

Embodiment 3

[0033] Dissolve 5 g of carboxymethyl chitin dry powder (molecular weight: 840,000 Daltons, degree of deacetylation: 7.99%) in 75 mL of water for injection, stir well, then add 1.5 g of lysine and 0.25 g of 4-(4,6 -dimethoxytriazin-2-yl)-4-methylmorpholine hydrochloride. After mixing, the pH value of the reaction solution was adjusted to 7.2 with 1M HCl, and placed at 4° C. for 240 h.

[0034] The mixture obtained by the reaction was homogenized, and slowly added dropwise 3 times the volume of ethanol of the mixture under stirring, the dry powder was washed with ethanol 5 times, dried in vacuum for 30min, and then dissolved in 200mL of water for injection. Stir thoroughly and evenly, and adjust the pH value to 7.0 with 1M HCl to obtain a transparent and uniform critical state gel. And canned in a disposable glass syringe, sterilized at 121° C. for 15 minutes to obtain carboxymethyl chitin critical state hydrogel that can be used for intra-articular injection.

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