CN114533942A - Polysaccharide hemostatic material, preparation method and application thereof - Google Patents
Polysaccharide hemostatic material, preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a polysaccharide hemostatic material and a preparation method and application thereof. The invention can generate physical and chemical effects with the whole blood components through the synergistic effect of hydrophilicity and hydrophobicity, promote the whole blood components to be quickly gelled within 10-30s, and enhance the hemostatic effect of the material.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to a polysaccharide hemostatic material for promoting blood gelation and a preparation method thereof.
Background
Bleeding is one of the leading causes of death in trauma patients, with uncontrollable massive bleeding representing 90.9% of preventable traumatic deaths. Therefore, the realization of rapid and efficient hemostasis after bleeding from wounds has great significance for improving the survival rate of bleeding patients and the battlefield rescue rate.
At present, the blood coagulation routes of the hemostatic materials are only divided into three categories: firstly, the hemostatic material is utilized to improve the concentration of blood coagulation factors in blood, thereby enhancing the physiological blood coagulation effect; secondly, promoting blood to gel by utilizing the physical and chemical action between the hemostatic material and the blood component, thereby forming blood clots to physically block bleeding parts; thirdly, the strong viscosity of the hemostatic material is utilized to directly block the bleeding site, thereby realizing rapid hemostasis. Among them, the first type of pathway has a slow response speed, and the third type of pathway is prone to cause secondary bleeding when the strongly viscous hemostatic material is removed, so that the second type of coagulation pathway is a currently preferred scheme for preparing the rapid hemostatic material.
The existing hemostatic materials mainly promote blood gelation through physicochemical action with single components of blood. The main components of blood are blood cells, plasma proteins and water. At present, the hemostatic material for promoting blood gelation is mainly used for causing blood gelation by aggregating blood cells in blood or absorbing water in blood, and has the defects of long action time of the hemostatic material and the blood, slow time for promoting blood gelation, weak mechanical property of formed blood gel and the like, and the stable and rapid hemostasis cannot be realized.
Therefore, in view of the defects in the prior art, the inventor designs a polysaccharide hemostatic material for rapidly promoting blood gelation by realizing physical and chemical actions with blood components through the synergistic action of hydrophilic and hydrophobic properties aiming at the main components of red blood cells, plasma proteins and water in blood, shortens the action time of the hemostatic material and the blood components, accelerates the blood gelation promotion speed of the hemostatic material in a quantitative manner, and improves the mechanical properties of the formed blood gel.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the technical problem to be solved by the present invention is to develop a hemostatic material that promotes blood gelation rapidly and stably.
In order to achieve the aim, the invention provides a polysaccharide hemostatic material, a preparation method and application thereof, and the preparation method comprises the preparation of a hydrophobic modified polysaccharide material, the preparation of a hydrophilic modified polysaccharide material and the preparation of a hydrophilic and hydrophobic synergistic polysaccharide hemostatic material for promoting blood gelation.
The invention discloses a polysaccharide hemostatic material in a first aspect, which specifically comprises the following steps:
step 1, adding a hydrophobic functional substance and EDC/NHS into a water-soluble polysaccharide solution, grafting the hydrophobic functional substance on a polysaccharide macromolecular main chain through a coupling reaction, and preparing a hydrophobically modified polysaccharide material through precipitation, washing and vacuum drying.
And 2, adding a hydrophilic functional substance and EDC/NHS into the water-soluble polysaccharide solution, grafting the hydrophilic functional substance on a polysaccharide macromolecular main chain through a coupling reaction, and dialyzing and freeze-drying to obtain the hydrophilic modified polysaccharide material.
And 3, dissolving the hydrophobically modified polysaccharide material and the hydrophilically modified polysaccharide material in a specific solvent according to a certain molar ratio, uniformly mixing, freezing by using liquid nitrogen, and freeze-drying to prepare the hydrophilic-hydrophobic synergistic polysaccharide hemostatic material for promoting blood gelation.
Further, the concentration of the polysaccharide dissolved in the step 1 and the step 2 is 10-50 mg/mL.
Further, the molar ratio of the polysaccharide dissolved in the step 1 to the added hydrophobic functional substance is 5:1-20: 1.
Further, the molar ratio of the solubilized polysaccharide in step 1 to the added coupling reaction activators EDC/NHS was 1: 1: 1.
further, the molar ratio of the polysaccharide dissolved in the step 2 to the hydrophilic functional substance added is 1:0.5-1: 2.
Further, the molar ratio of the solubilized polysaccharide in step 2 to the added coupling reaction activators EDC/NHS was 1: 2: 2.
further, in step 3 the hydrophobically modified polysaccharide material and the hydrophilically modified polysaccharide material are mixed in a specific solvent in a molar ratio of 1:0.1 to 1: 10.
Preferably, the water-soluble polysaccharide in the preparation process is selected from one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid or aminodextran.
Preferably, the hydrophobic functional substance in the preparation process is selected from one or more of n-octanoic acid, dodecanoic acid, hexadecanoic acid, caprylic anhydride, dodecanoic anhydride, hexadecanoic anhydride, n-octylamine, n-dodecylamine, n-hexadecylamine or n-octadecylamine.
Preferably, the hydrophilic functional substance in the preparation process is selected from one or more of 3, 4-dihydroxyphenyl propionic acid, 3,4, 5-trihydroxybenzoic acid, 4-carboxyphenylboronic acid, dopamine hydrochloride and 3-aminophenylboronic acid hydrochloride.
Preferably, the specific solvent in the preparation process is selected from one or more of PBS buffer, MES buffer, HEPES buffer, hydrochloric acid, acetic acid, lactic acid or tranexamic acid aqueous solution with different mass fractions.
The second aspect of the invention discloses a polysaccharide hemostatic material, which is prepared by physically crosslinking a hydrophobically modified polysaccharide material and a hydrophilically modified polysaccharide material, and comprises a water-soluble polysaccharide material, a hydrophobic functional substance and a hydrophilic functional substance, wherein the hydrophobic functional substance and the hydrophilic functional substance are respectively grafted on different polysaccharide macromolecule main chains. The third aspect of the invention provides a polysaccharide hemostatic material or a use of a method of preparing a polysaccharide hemostatic material in the preparation of a hemostatic dosage form.
The invention has the beneficial effects that: the designed polysaccharide hemostatic material can generate physicochemical action with the whole blood components (blood cells, plasma protein and water) through the synergistic action of hydrophilicity and hydrophobicity, so that the whole blood components are promoted to be rapidly gelled within 10-30s, and the hemostatic effect of the material is enhanced; the polysaccharide hemostatic material with hydrophilic-hydrophobic synergistic and blood gelation promoting effects can be widely used as a raw material for preparing various hemostatic dosage forms (such as powder, sponge, bandage, gauze, spray and the like), and has wide application prospects in the fields of military, medical and other rapid hemostasis.
Drawings
FIG. 1 is a reaction scheme of the preparation process of the present invention;
FIG. 2 is a topographical view of a hemostatic material of the present invention;
FIG. 3 is a graph showing the effect of tube inversion in the in vitro coagulation test of the present invention.
Detailed Description
The technical contents of the preferred embodiments of the present invention will be more clearly and easily understood by referring to the drawings attached to the specification. The present invention may be embodied in many different forms of embodiments and the scope of the invention is not limited to the embodiments set forth herein.
Example 1
2g of chitosan was dissolved in 100mL of 0.2M acetic acid and 100mL of ethanol was added followed by 364uL of caprylic anhydride and 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 1:3 molar ratio in a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with hydrophilicity and hydrophobicity coordination and blood gelation promotion.
Example 2
2g of chitosan was dissolved in 100mL of 0.2M acetic acid, and 100mL of ethanol was added, heated to 45 deg.C, followed by the addition of 0.2g of dodecanoic anhydride, and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 1:3 molar ratio in a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with hydrophilicity and hydrophobicity coordination and blood gelation promotion.
Example 3
2g of chitosan was dissolved in 100mL of 0.2M acetic acid, and 100mL of ethanol was added, heated to 65 ℃, followed by the addition of 0.154g of dodecanoic anhydride, and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 1:3 molar ratio in a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with hydrophilicity and hydrophobicity coordination and blood gelation promotion.
Example 4
2g of chitosan was dissolved in 100mL of 0.2M acetic acid, and 100mL of ethanol was added, heated to 65 ℃, followed by the addition of 0.154g of dodecanoic anhydride, and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.17g of 3,4, 5-trihydroxybenzoic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 1:3 molar ratio in a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with hydrophilicity and hydrophobicity coordination and blood gelation promotion.
Example 5
2g of chitosan was dissolved in 100mL of 0.2M acetic acid, and 100mL of ethanol was added, heated to 65 ℃, followed by the addition of 0.154g of dodecanoic anhydride, and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.03g of 4-carboxyphenylboronic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 1:3 molar ratio in a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with hydrophilicity and hydrophobicity coordination and blood gelation promotion.
Example 6
2g of chitosan was dissolved in 100mL of 0.2M acetic acid, and 100mL of ethanol was added, heated to 65 ℃, followed by the addition of 0.154g of dodecanoic anhydride, and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding 3mL of 5M sodium hydroxide to adjust the pH value to 10, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified chitosan;
dissolving 2g of chitosan in 100mL of 0.2M acetic acid, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.17g of 3,4, 5-trihydroxybenzoic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified chitosan;
dissolving the hydrophobically modified chitosan and the hydrophilically modified chitosan in a 0.2M acetic acid aqueous solution according to a molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the chitosan hemostatic material with synergetic hydrophilicity and hydrophobicity and capable of promoting blood gelation.
Example 7
2g of aminodextran was dissolved in 50mL of deionized water and 50mL of ethanol was added, the pH was adjusted to 5.0, followed by 364uL of caprylic anhydride and 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in a molar ratio of 1:3 into a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 8
2g of aminodextran are dissolved in 50mL of deionized water and 50mL of ethanol are added, heated to 45 ℃ to adjust the pH to 5.0, followed by the addition of 0.2g of dodecanoic anhydride and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in a molar ratio of 1:3 into a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 9
2g of aminodextran are dissolved in 50mL of deionized water and 50mL of ethanol are added, heated to 65 ℃ and the pH is adjusted to 5.0, followed by the addition of 0.154g of dodecanoic anhydride and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in a molar ratio of 1:3 into a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 10
2g of aminodextran are dissolved in 50mL of deionized water and 50mL of ethanol are added, heated to 45 ℃ to adjust the pH to 5.0, followed by the addition of 0.2g of dodecanoic anhydride and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.17g of 3,4, 5-trihydroxybenzoic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing with acidified deionized water for 3 days, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in a molar ratio of 1:3 into a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 11
2g of aminodextran are dissolved in 50mL of deionized water and 50mL of ethanol are added, heated to 45 ℃ to adjust the pH to 5.0, followed by the addition of 0.2g of dodecanoic anhydride and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.02g of 4-carboxyphenylboronic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in a molar ratio of 1:3 into a 1% tranexamic acid aqueous solution, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 12
2g of aminodextran are dissolved in 50mL of deionized water and 50mL of ethanol are added, heated to 65 ℃ and the pH is adjusted to 5.0, followed by the addition of 0.154g of dodecanoic anhydride and the addition of 2.38g of EDC and 1.43g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified aminodextran;
dissolving 2g of aminodextran in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, then sequentially adding 1.19g of 3, 4-dihydroxyphenyl propionic acid, 2.38g of EDC and 1.43g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified aminodextran;
dissolving the hydrophobically modified aminodextran and the hydrophilically modified aminodextran in deionized water according to the molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic aminodextran hemostatic material for promoting blood gelation.
Example 13
2g of hyaluronic acid was dissolved in 50mL of deionized water and 50mL of ethanol was added to adjust the pH to 5.0, followed by 219uL of n-octylamine and 1.02g of EDC and 0.61g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified hyaluronic acid;
dissolving 2g of hyaluronic acid in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.5g of dopamine hydrochloride, 1.02g of EDC and 0.61g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified hyaluronic acid;
dissolving the hydrophobically modified hyaluronic acid and the hydrophilically modified hyaluronic acid into 1% tranexamic acid aqueous solution according to the molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic hyaluronic acid hemostatic material for promoting blood gelation.
Example 14
2g of hyaluronic acid was dissolved in 50mL of deionized water and 50mL of ethanol was added to adjust the pH to 5.0, followed by 219uL of n-octylamine and 1.02g of EDC and 0.61g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified hyaluronic acid;
dissolving 2g of hyaluronic acid in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.46g of 3-aminophenylboronic acid hydrochloride, 1.02g of EDC and 0.61g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified hyaluronic acid;
dissolving the hydrophobically modified hyaluronic acid and the hydrophilically modified hyaluronic acid into 1% tranexamic acid aqueous solution according to the molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic hyaluronic acid hemostatic material for promoting blood gelation.
Example 15
2g of hyaluronic acid was dissolved in 50mL of deionized water and 50mL of ethanol was added to adjust the pH to 5.0, followed by 219uL of n-octylamine and 1.02g of EDC and 0.61g of NHS. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified hyaluronic acid;
dissolving 1g of hyaluronic acid in 50mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.5g of dopamine hydrochloride, 1.02g of EDC and 0.61g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified hyaluronic acid;
dissolving the hydrophobically modified hyaluronic acid and the hydrophilically modified hyaluronic acid in deionized water according to a molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic hyaluronic acid hemostatic material for promoting blood gelation.
Example 16
2g of sodium alginate was dissolved in 100mL of deionized water and 100mL of ethanol was added followed by 837uL of n-octylamine, the pH adjusted to 3.4 and 1.94g of EDC and 1.16g of NHS were added. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified sodium alginate;
dissolving 2g of sodium alginate in 100mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.96g of dopamine hydrochloride, 1.94g of EDC and 1.16g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified sodium alginate;
dissolving the hydrophobically modified sodium alginate and the hydrophilically modified sodium alginate in a 1% tranexamic acid aqueous solution according to a molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic sodium alginate hemostatic material for promoting blood gelation.
Example 17
2g of sodium alginate was dissolved in 100mL of deionized water and 100mL of ethanol was added followed by 837uL of n-octylamine, the pH adjusted to 3.4 and 1.94g of EDC and 1.16g of NHS were added. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified sodium alginate;
dissolving 2g of sodium alginate in 100mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.88g of 3-aminophenylboronic acid hydrochloride, 1.94g of EDC and 1.16g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified sodium alginate;
dissolving the hydrophobically modified sodium alginate and the hydrophilically modified sodium alginate in a 1% tranexamic acid aqueous solution according to a molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic sodium alginate hemostatic material for promoting blood gelation.
Example 18
2g of sodium alginate was dissolved in 100mL of deionized water and 100mL of ethanol was added followed by 837uL of n-octylamine, the pH adjusted to 3.4 and 1.94g of EDC and 1.16g of NHS were added. Reacting overnight, adding excessive acetone for precipitation, filtering, washing with water and ethanol for 5 times, and drying in a vacuum oven to obtain hydrophobically modified sodium alginate;
dissolving 2g of sodium alginate in 100mL of deionized water, introducing nitrogen for 10 minutes, adjusting the pH to 5.0, sequentially adding 0.96g of dopamine hydrochloride, 1.94g of EDC and 1.16g of NHS, reacting overnight, dialyzing for 3 days with acidified deionized water, and freeze-drying to obtain hydrophilic modified sodium alginate;
dissolving the hydrophobically modified sodium alginate and the hydrophilically modified sodium alginate in deionized water according to the molar ratio of 1:3, stirring for 4h, freezing and freeze-drying to obtain the hydrophilic-hydrophobic synergistic sodium alginate hemostatic material for promoting blood gelation.
Example 19
The in vitro coagulation performance of the hydrophilic-hydrophobic synergistic blood-gelation-promoting chitosan hemostatic material prepared in example 2 was tested by a reverse tube experiment. The chitosan hemostatic material prepared in the embodiment 2 is dissolved in deionized water according to the mass fraction of 0.5 wt%, 1mL of the solution is taken to be mixed with 1mL of human whole blood containing EDTA anticoagulant, the mixture is swirled for 5s, a tube inversion experiment is carried out, and the blood gel condition is observed.
The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.
Claims (10)
1. The preparation method of the polysaccharide hemostatic material is characterized by comprising the following steps:
step 1, adding a hydrophobic functional substance and EDC/NHS into a water-soluble polysaccharide solution, grafting the hydrophobic functional substance onto a polysaccharide macromolecular main chain through a coupling reaction, and preparing a hydrophobically modified polysaccharide material through precipitation, washing and vacuum drying;
step 2, adding a hydrophilic functional substance and EDC/NHS into a water-soluble polysaccharide solution, grafting the hydrophilic functional substance on a polysaccharide macromolecular main chain through a coupling reaction, and dialyzing and freeze-drying to obtain a hydrophilic modified polysaccharide material;
and 3, dissolving the hydrophobically modified polysaccharide material and the hydrophilically modified polysaccharide material in a solvent, uniformly mixing, freezing by using liquid nitrogen, and freeze-drying to prepare the hydrophilic-hydrophobic synergistic polysaccharide hemostatic material for promoting blood gelation.
2. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the water-soluble polysaccharide in step 1 is selected from one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid or aminodextran.
3. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the hydrophobic functional substance in step 1 is selected from one or more of n-octanoic acid, dodecanoic acid, hexadecanoic acid, octanoic anhydride, dodecanoic anhydride, hexadecanoic anhydride, n-octylamine, n-dodecylamine, n-hexadecylamine and n-octadecylamine.
4. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the water-soluble polysaccharide in step 2 is selected from one or more of chitosan, hydroxymethyl chitosan, carboxypropyl chitosan, chitosan oligosaccharide, sodium alginate, hyaluronic acid or aminodextran.
5. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the hydrophilic functional substance in step 2 is selected from one or more of 3, 4-dihydroxyphenyl propionic acid, 3,4, 5-trihydroxybenzoic acid, 4-carboxyphenylboronic acid, dopamine hydrochloride and 3-aminophenylboronic acid hydrochloride.
6. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the solvent in step 3 is selected from one or more of PBS buffer, MES buffer, HEPES buffer, hydrochloric acid, acetic acid, lactic acid or tranexamic acid aqueous solution.
7. The method for preparing polysaccharide hemostatic material according to claim 1, wherein the hydrophobically modified polysaccharide material and the hydrophilically modified polysaccharide material are mixed in step 3 in a molar ratio of 1:0.1 to 1: 10.
8. The method for preparing a polysaccharide hemostatic material according to any one of claims 1-6, wherein the polysaccharide solution concentration is 10-50 mg/mL.
9. The polysaccharide hemostatic material is characterized by being prepared by physically crosslinking a hydrophobically modified polysaccharide material and a hydrophilically modified polysaccharide material, and comprising a water-soluble polysaccharide material, a hydrophobic functional substance and a hydrophilic functional substance, wherein the hydrophobic functional substance and the hydrophilic functional substance are respectively grafted on different polysaccharide macromolecule main chains.
10. Use of a polysaccharide haemostatic material according to claim 9 or a method of preparing a polysaccharide haemostatic material according to any of claims 1-8 in the preparation of a haemostatic dosage form.
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