CN106334209A - Polydopamine modified chitosan hemostatic dressing - Google Patents

Abstract

The invention discloses a polydopamine modified chitosan hemostatic dressing, which comprises: (a) a porous interpenetrating network formed by chitosan and polydopamine; (b) at least one calcium salt. The invention also discloses a preparation method of polydopamine modified chitosan hemostatic dressing. The polydopamine-modified chitosan hemostatic sponge prepared by the method of the invention not only has good hemostatic effect, but also has good adhesion performance to biological tissues such as skin and organs.

Description

Polydopamine modified chitosan hemostatic dressing

technical field

The invention belongs to the technical field of hemostatic dressing for medical surgery, and relates to a polydopamine-modified chitosan hemostatic dressing with good tissue adhesion performance and a preparation method thereof.

Background technique

Chitosan, derived from chitin, is a natural polymer polysaccharide whose yield is second only to cellulose in nature. Chitosan has many physiological activities, such as antibacterial, lipid-lowering, hemostasis, promoting healing, anti-tumor, anti-oxidation, and improving immunity. At the same time, since they are all derived from organisms, they are non-irritating, non-antigen-immune, have good histocompatibility, and can be degraded by lysozyme widely present in animal tissues, resulting in non-toxic and biologically It is a natural metabolite that is completely absorbed by the body. Therefore, it shows good application prospects in many aspects such as medicine, biology, chemical industry, environment, and food.

As raw materials for wound dressings, chitin and chitosan have become a hotspot in the research of functional biological hemostatic materials because of their excellent properties such as hemostasis, healing promotion, anti-inflammation, pain relief, scar reduction, and antibacterial properties. As disclosed in CN1167366, a composite sponge biological dressing made of chitosan, collagen and calcium alginate has good biocompatibility, adhesion, promotes wound healing and hemostasis. CN1217706 discloses a sponge hemostatic material made of chitosan/chitin as a raw material, which has good hemostatic activity and bioactivity to promote tissue repair and strong adhesion. In CN1229148, a kind of anti-adhesion film prepared with water-soluble chitosan as the main raw material is disclosed, which has the functions of hemostasis, protection and repair and promotion of wound healing. In CN100411690, a method for preparing a porous material for hemostasis and wound dressing with chitosan and sodium alginate is disclosed. The prepared porous material has a higher water absorption rate and a shorter hemostasis time. In CN100415304, a method for preparing a biodegradable hemostatic sponge material with human-like collagen and chitosan is disclosed. In CN101502667, a chitosan transparent hydrogel wound dressing prepared by polyacrylic acid, polyvinylpyrrolidone and chitosan is disclosed, which has the characteristics of anti-inflammatory, hemostasis and high water absorption. CN101897990 discloses a composition for inhibiting scars and promoting rapid wound healing, which is composed of chitosan, acidic polysaccharide and Panax notoginseng saponins. Chitosan has a good hemostatic effect, but the adhesion to the wound still needs to be improved.

Mussels are crustaceans commonly found in coastal and offshore waters, especially in cold waters. They can stick themselves to the reefs on the coast or the bottom of ships by secreting super strong mucus, and they can still adhere tightly to the bottom of ships even when they are washed by rough waves. Not only that, they can adhere themselves extremely firmly to any material such as metal, glass, polymer and mineral surfaces, and even firmly adhere to Teflon surfaces that are extremely difficult to adhere. Forms strong hydrogen bonds with polar polymers such as proteins. The super waterproof adhesion and universal adhesion properties of mussels are very attractive. The study found that mussels secrete a very special mucus through their silk glands, which solidifies immediately after encountering seawater to form an adhesive disc, which is tightly attached to the substrate. The main component of mucus is mussel adhesive protein, and one of its most unique structural features is the amino acid dopamine (dihydroxyphenylalanine). The catechol group (also known as catechol) in dopamine has chemical versatility and affinity diversity, which is the key to the super adhesive performance of mussels. In order to improve the tissue adhesion of the chitosan-based hemostatic sponge material, CN104013990 discloses a chitosan with a catechol structure by reacting chitosan with dopamine or a compound with a catechol-based structure material, the hemostatic sponge is said to have good tissue affinity.

Contents of the invention

The purpose of the present invention is to provide a polydopamine modified chitosan hemostatic dressing.

Another object of the present invention is to provide a method for preparing polydopamine-modified chitosan hemostatic dressing.

detailed description

The invention provides a polydopamine modified chitosan hemostatic dressing, which is a porous structure, which comprises:

(a) porous interpenetrating network formed by chitosan and polydopamine;

(b) at least one calcium salt.

Chitosan in the described chitosan hemostatic dressing can be unmodified chitosan, also can be modified chitosan salt, such as acetate, hydrochloride, lactate of chitosan Salt etc., can also be through other chemically modified chitosan, such as carboxyethyl chitosan etc. The degree of deacetylation of the chitosan is 50-99%, the optimum is 70-90%. The chitosan has a weight-average molecular weight of 10,000-150,000, preferably 15,000-80,000. The weight content of chitosan in the hemostatic dressing is 85-98%.

The polydopamine is the hydrochloride of dopamine obtained by self-polymerization after adjusting the pH value to alkaline. The weight content of polydopamine in the hemostatic dressing is 2-20%.

Described calcium salt is the salt that generates after calcium hydroxide is neutralized with inorganic or organic acid, both can be inorganic salt such as calcium chloride etc., also can be organic acid salt such as calcium acetate, calcium lactate, calcium salicylate, Calcium gallate, calcium caffeate, etc. The weight content of calcium salt in the hemostatic dressing is 5-10%.

In order to improve the softness and comfort of the chitosan hemostatic dressing, a plasticizer can also be contained in the chitosan hemostatic dressing. The weight content of the plasticizer in the hemostatic dressing is 0-10%. The plasticizer is glycerin, polyethylene glycol 200, polyethylene glycol 400, propylene glycol and the like.

Another aspect of the present invention provides a preparation method of polydopamine-modified chitosan hemostatic dressing, comprising the following steps: a. adding chitosan to an appropriate amount of water, and configuring it into a solution or suspension with a mass concentration of 0.5-5%, making the shell The polysaccharide is completely dissolved or fully swollen; b. adding dopamine hydrochloride to the chitosan solution to fully dissolve; c. adjusting the pH value of the chitosan solution or suspension containing dopamine hydrochloride to alkaline with calcium hydroxide , continuously stirring to make dopamine self-polymerize to form polydopamine; d. After adjusting the pH value to neutral or acidic with acid, stir until the chitosan is completely dissolved; e. Add plasticizer to the solution, stir evenly, and freeze-dry , to obtain a polydopamine-modified chitosan sponge; f. hot pressing the chitosan sponge at 70-90° C. to obtain a chitosan hemostatic dressing with a density of 0.15-0.5 g/cm ³ . The polydopamine-modified chitosan hemostatic dressing prepared by the method of the invention not only has good hemostatic effect, but also has good adhesion performance to biological tissues such as skin and organs.

testing method

Hemostatic performance: Take a 1cm×1cm chitosan hemostatic dressing and put it in a glass bottle, drop 120μl of rabbit whole blood (containing 1:6 anticoagulant), add 10ml of water along the bottle wall after acting at 37°C for 30s, After 10 minutes, the erythrocytes that did not coagulate were dissolved in water, and the absorbance value at wavelength λ _540nm was used to characterize the amount of hemoglobin dissolved in water to evaluate the hemostatic performance. The larger the absorbance value, the more red blood cells dissolved in the water and the worse the hemostatic performance.

Adhesion performance: The adhesion performance of chitosan hemostatic dressing was measured by Instron3366 electronic universal tensile testing machine. The chitosan hemostatic dressing was pasted on the fixed fixture, and the fresh pig large intestine was cut into 1cm squares and fixed ^on the movable fixture. The mobile fixture is pressed on the fixed fixture at a speed of 0.1mm/min, and then left at a speed of 0.1mm/min after holding the pressure at 0.1N for 3 minutes. The maximum adhesion force at the time of disengagement is used to characterize the adhesion of the chitosan hemostatic dressing to the tissue performance.

Example 1

Add chitosan with a deacetylation degree of 85% and a weight-average molecular weight of 30,000 to ultrapure water, stir until it swells completely, and form a suspension with a mass concentration of 2%, and add 0.2% dopamine relative to the mass of ultrapure water After the hydrochloride is completely dissolved, add an appropriate amount of saturated calcium hydroxide aqueous solution dropwise, adjust the solution to alkaline, and stir until the dopamine is completely polymerized to form a dark brown solution. After being neutralized to neutral with hydrochloric acid, 2% glacial acetic acid relative to the quality of ultrapure water is added to the solution, and stirred until the chitosan is completely dissolved. Then add 0.5% glycerin relative to the mass of ultrapure water, and stir evenly. The prepared polydopamine-chitosan solution is defoamed and freeze-dried to obtain a polydopamine-modified chitosan sponge. The sponge was hot-pressed at 80°C to obtain a polydopamine-modified chitosan hemostatic dressing, and its adhesion properties are shown in Table 1.

Example 2

Dissolve chitosan lactate with a deacetylation degree of 90% and a weight average molecular weight of 15,000 in ultrapure water, and stir until completely dissolved to form a solution with a mass concentration of 3%. Add 0.4% dopamine hydrochloride relative to the quality of ultrapure water to the solution, add an appropriate amount of saturated calcium hydroxide aqueous solution after completely dissolving, adjust the solution to alkaline, and stir until the dopamine is completely polymerized to form a dark brown solution. After adding hydrochloric acid to the solution to adjust the pH value of the solution to neutral, stir until the chitosan is completely dissolved, then add 0.5% PEG200 relative to the quality of ultrapure water, and stir evenly. The prepared polydopamine-chitosan lactate solution is defoamed and freeze-dried to obtain the polydopamine-modified chitosan lactate sponge. The sponge was hot-pressed at 80°C to obtain polydopamine-modified chitosan lactate hemostatic dressing, and its adhesion properties are shown in Table 1.

Example 3

Chitosan with a deacetylation degree of 80% and a weight-average molecular weight of 50,000 is added into ultrapure water, and stirred until it swells completely to form a suspension with a mass concentration of 1.5%. Add 0.5% dopamine hydrochloride relative to the quality of ultrapure water, dissolve and drop in an appropriate amount of saturated calcium hydroxide aqueous solution, adjust the solution to alkaline, and stir until the dopamine is completely polymerized to form a dark brown solution. After adding hydrochloric acid to the solution to adjust to neutrality, add 3% acetic acid relative to the ultrapure water quality, heat to completely dissolve the chitosan, then add 1% glycerin relative to the ultrapure water quality, and stir evenly. After the prepared chitosan polydopamine solution is freeze-dried, polydopamine-modified chitosan sponge is obtained. The polydopamine-modified chitosan hemostatic dressing was obtained by hot-pressing the sponge at 75°C, and its adhesion properties are shown in Table 1.

Example 4

Add carboxyethyl chitosan with a deacetylation degree of 95% and a weight-average molecular weight of 20,000 to ultrapure water, stir until completely dissolved, and form a suspension with a mass concentration of 1.5%. Add 0.5% dopamine hydrochloride relative to the quality of ultrapure water, dissolve and drop in an appropriate amount of saturated calcium hydroxide aqueous solution, adjust the solution to alkaline, and stir until the dopamine is completely polymerized to form a dark brown solution. After adjusting the hydrochloric acid to neutrality in the solution, add 3% caffeic acid relative to the ultrapure water quality, heat to completely dissolve the chitosan, then add 1% glycerin relative to the ultrapure water quality, and stir evenly. After the prepared chitosan polydopamine solution is freeze-dried, polydopamine-modified chitosan sponge is obtained. The polydopamine-modified chitosan hemostatic dressing was obtained by hot-pressing the sponge at 75°C, and its adhesion properties are shown in Table 1.

Comparative example 1

Chitosan with a deacetylation degree of 80% and a weight-average molecular weight of 50,000 is added to ultrapure water, stirred until it swells completely, and then added with 2% glacial acetic acid relative to the quality of ultrapure water to completely dissolve chitosan, and then Add 0.5% glycerin relative to the quality of ultrapure water, and stir evenly. After the prepared chitosan solution is freeze-dried, the chitosan sponge is obtained. The chitosan hemostatic dressing was obtained by heat-pressing the sponge at 75°C, and its adhesion properties are shown in Table 1.

Table 1 Adhesion performance of chitosan hemostatic dressing

Claims (7)

1. a kind of poly-dopamine modified lithium shitosan bleeding-stopping dressing, comprising:

(a) shitosan and poly-dopamine；

(b) at least one calcium salt.

2. poly-dopamine modified lithium shitosan bleeding-stopping dressing as claimed in claim 1, wherein shitosan is in bleeding-stopping dressing In content be 85-98 weight %；Content in bleeding-stopping dressing for the poly-dopamine is 2-20 weight %；Calcium Content in bleeding-stopping dressing for the salt is 5-10 weight %；Content in bleeding-stopping dressing for the plasticizer is 0-10 Weight %.

3. poly-dopamine modified lithium shitosan bleeding-stopping dressing as claimed in claim 1 or 2, wherein shitosan gather for shell Sugar and/or the derivant of shitosan, the such as acetate of shitosan, hydrochlorate, lactate, carboxymethyl chitosan Sugar, carboxyetbyl chitosan etc..

4. the poly-dopamine modified lithium shitosan bleeding-stopping dressing as described in any one in claim 1-3, wherein shell gather The deacetylation of sugar is 50-99%, and optimum is 70-90%.

5. the poly-dopamine modified lithium shitosan bleeding-stopping dressing as described in any one in claim 1-4, wherein shell gather The weight average molecular weight of sugar is 10,000～150,000, and optimum is 1.5 ten thousand～80,000.

6. poly-dopamine modified lithium shitosan bleeding-stopping dressing as claimed in claim 1 or 2, calcium salt therein is chlorination Calcium, calcium acetate, calcium lactate, calcium salicylate, gallic acid calcium, caffeic acid calcium etc..

7. a kind of side preparing poly-dopamine modified lithium shitosan bleeding-stopping dressing described in any one in claim 1-6 Method, comprises the steps: that a. adds shitosan in appropriate water, is configured to mass concentration 0.5-5% Solution or suspension, so that shitosan is completely dissolved or fully swelling；B. add many toward in chitosan solution Bar amine hydrochlorate fully dissolves；C. the chitosan solution or outstanding containing dopamine hydrochloride is adjusted with calcium hydroxide The ph value of supernatant liquid to alkalescence, continuously stirred make dopamine autohemagglutination formed poly-dopamine；D. with sour by ph Value is adjusted to neutrality or acidity, stirs and is completely dissolved to shitosan；E. add plasticizer toward in solution, After stirring, lyophilization, obtain the chitosan sponge of poly-dopamine modified lithium；F. by chitosan sponge In 70-90 DEG C of hot pressing, obtaining density is 0.15-0.5g/cm³Shitosan bleeding-stopping dressing.