A starch-based medical adhesive and its preparation method and application

Abstract

The present invention discloses a starch-based medical adhesive and its preparation method and application, specifically relating to the field of biomedical materials technology. The method comprises first adding modified starch 1 to water, heating and stirring in an oil bath for gelatinization to obtain a modified starch 1 solution; adding modified starch 2 to water, heating and stirring in an oil bath for gelatinization to obtain a modified starch 2 solution; then mixing the modified starch 1 solution and the modified starch 2 solution, stirring evenly to obtain a modified starch complex; finally, freezing the modified starch complex at low temperature, freeze-drying it, and crushing the freeze-dried modified starch complex to obtain a starch-based medical adhesive. The medical adhesive of the present invention has good biocompatibility, can be degraded into non-toxic and harmless products in the body, has strong wet tissue adhesion strength and good tissue compliance, is simple to process, can be directly applied to skin wounds, deep wounds, and wounds in areas that are difficult to reach through surgery, and is simple and convenient to use.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a starch-based medical adhesive and a preparation method and application thereof. Background Art

[0002] As the largest organ in the human body, the integrity of the skin's barrier function plays an irreplaceable role in resisting pathogen invasion, regulating water balance, and maintaining internal environmental homeostasis. However, mechanical trauma, thermal damage, etc. often lead to damage to the skin barrier and cause local or systemic complications. Although traditional wound closure technologies such as sutures and staplers can provide mechanical support, there is a risk of causing secondary damage and stress concentration at the perforation site, leading to scar formation. In addition, this type of closure technology is difficult to completely close the wound, and it is easy to cause tissue fluid leakage and pathogen invasion, thereby triggering an inflammatory response and hindering wound healing.

[0003] Currently, medical adhesives used clinically mainly include cyanoacrylates and fibrin glue. Chinese patents CN112266337A and CN116392627A are all cyanoacrylate adhesives. Although cyanoacrylate adhesives can quickly close wounds, they are prone to foreign body reactions or chronic inflammation due to defects such as non-degradability, heat release during polymerization, and poor tissue compliance. Chinese patents CN110711264A and CN109529098A are all adhesives with added fibrin. Although fibrin glue has good biocompatibility, its adhesion and mechanical strength are insufficient, and some of its internal components may cause allergic reactions in organisms.

[0004] An ideal medical adhesive should simultaneously possess the following properties: 1. Good biocompatibility (avoiding foreign body or allergic reactions); 2. Degradability with non-toxic degradation byproducts; 3. Good wet tissue adhesion (able to overcome the effects of interfacial water on adhesion); and 4. Good tissue compliance (adapting to tissue deformation and avoiding stress concentration).

[0005] Starch is a natural high-molecular-weight polysaccharide formed by the polymerization of D-glucose through α-glycosidic bonds. Its molecular structure exhibits significant heterogeneity: amylose, with linear glucose units linked by α-1,4-glycosidic bonds, forms an unbranched chain structure; amylopectin, on the other hand, exhibits a highly branched topology, with a backbone composed of α-1,4-glycosidic bonds, from which side chains branch out every 24-30 glucose residues through α-1,6-glycosidic bonds. Furthermore, these branch points are not randomly distributed but rather clustered and periodically arranged, with short branches clustered at nanometer-scale intervals along the backbone to form clustered supramolecular assemblies. This unique clustered topology gives starch granules their high-density packing properties and, through interchain hydrogen bonding, creates locally ordered semi-crystalline regions, a key characteristic that distinguishes starch from other polysaccharides. The aggregation structure of starch molecules has a crucial influence on their physical and chemical properties. In natural starch granules, amylose molecules are primarily distributed in amorphous regions, while the clustered branches of amylopectin molecules form a double helical structure and are orderly arranged to form crystalline regions. This semi-ordered structure makes starch granules insoluble in water at room temperature, but gelatinization will occur in high-temperature aqueous solution. That is, when the temperature exceeds the gelatinization starting temperature, water molecules will penetrate into the interior of the granules, destroying the crystal structure and stretching the molecular chains.

[0006] Starch has excellent biocompatibility and biodegradability due to its unique molecular and aggregated structure, making it a promising medical adhesive material. Examples include Chinese patents CN101497670A and CN108753202A. However, these starch adhesives primarily serve a hemostatic function, with bonding being a secondary function. Furthermore, their strength when used alone is insufficient for bonding, and they can break or peel off during movement after bonding, resulting in poor results. Chinese patent CN119552532A discloses a method for preparing a starch adhesive for corrugated paper. Although the starch adhesive described in this patent is also modified starch, it is modified with aldehyde groups. While this has high bonding ability, the toxicity of the aldehyde-modified starch limits its application in medical adhesives. Summary of the Invention

[0007] To this end, the present invention provides a starch-based medical adhesive and a preparation method and application thereof to solve the problems in the prior art.

[0008] Natural starch itself has two problems: first, its molecular chain structure lacks functional groups (only hydroxyl groups), and second, natural starch granules are semi-crystalline. These crystalline regions act as crosslinks, limiting the dissolution of the starch granules. These two limitations make natural starch granules difficult to use as bioadhesives. Therefore, the present invention addresses these two issues by introducing functional groups through chemical modification and then disrupting its crystal structure through gelatinization to enhance molecular diffusion. This two-pronged approach significantly improves the adhesion strength of the present material to wet tissue. Modified starch alone, without its crystal structure being disrupted, still limits the material's solubility, resulting in very low bonding strength between the two modified starches (low bulk strength) and low bonding strength between the material and tissue (low interfacial adhesion strength).

[0009] In order to achieve the above object, the present invention provides the following technical solutions:

[0010] According to the first aspect of the present invention, a method for preparing a starch-based medical adhesive is provided, the method comprising:

[0011] Step 1: Modified starch pretreatment

[0012] Add modified starch 1 to water, heat and stir in an oil bath to gelatinize, and obtain modified starch 1 solution; add modified starch 2 to water, heat and stir in an oil bath to gelatinize, and obtain modified starch 2 solution;

[0013] Step 2: Mix

[0014] Mixing the modified starch 1 solution and the modified starch 2 solution, stirring evenly, to obtain a modified starch complex;

[0015] Step 3: Freezing, drying and crushing

[0016] The modified starch complex is first subjected to low-temperature freezing treatment and then freeze-dried, and the freeze-dried modified starch complex is crushed to obtain a starch-based medical adhesive.

[0017] Furthermore, the modified starch 1 is one or more of carboxymethyl-modified starch, carboxyethyl-modified starch, carboxypropyl-modified starch, phosphate-modified starch, xanthate-modified starch, citrate-modified starch, acetate-modified starch, and acetylated diphosphate-modified starch.

[0018] Preparation method of modified starch 1:

[0019] NaOH was added to deionized water and stirred to dissolve. Isopropanol was then added, and the mixture was stirred and heated to 40°C. Subsequently, starch was added and nitrogen was introduced. After stirring for 1 hour, sodium chloroacetate / ethylene oxide / propylene oxide / phosphate / citrate / xanthate / acetic anhydride was added and allowed to react for 3 hours. After the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain modified starch 1 sample.

[0020] Furthermore, the modified starch 2 is starch modified with a quaternary ammonium salt and / or starch modified with a tertiary aminoalkyl group.

[0021] Preparation method of modified starch 2:

[0022] First, sodium hydroxide was dissolved in deionized water and magnetically stirred until the solution was clear. Simultaneously, 2,3-epoxypropyltrimethylammonium chloride / 2,3-epoxypropyl-N,N-dialkylamine was dispersed in deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, starch was evenly dispersed in deionized water, and the NaOH / EPTAC (or NaOH / DAEPA) mixture was added dropwise at a constant rate. The mixture was then reacted at 40°C for 24 hours to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (with 3-4 changes of water daily) to remove unreacted small molecular impurities. Finally, modified starch 2 was obtained by freeze-drying, pulverization, and sieving.

[0023] The modified starches 1 and 2 selected in the present invention have wet tissue adhesion, while other modified starches (such as N,N-dimethyldecylamine modified) or some modified starches that also carry positive and negative charge groups are insufficient in solubility and adhesion strength.

[0024] Furthermore, the starch is one or more of bean starch, tuber starch, sweet potato starch, potato starch, cereal starch, wheat starch, water chestnut starch, lotus root starch, and corn starch.

[0025] Furthermore, in step 1, the heating temperature is 40-300°C. Temperatures below 40°C can easily result in gelatinization failure or incomplete gelatinization. Using solvents to dissolve or lower the gelatinization temperature raises two issues: first, solubility temperature. Existing solvents typically have low solubility for starch at room temperature. Second, biosafety. Commonly used starch solvents are mostly organic reagents, which have certain toxicity issues and are difficult to completely remove during the preparation process.

[0026] Furthermore, in step 1, the concentrations of the modified starch 1 solution and the modified starch 2 solution are both 0.1%-10%.

[0027] Furthermore, in the step 2, the mass ratio of the modified starch 1 solution to the modified starch 2 solution is 0.1-0.9:0.9-0.1.

[0028] Furthermore, in step three, the temperature of the cryogenic freezing is -10 to -270°C.

[0029] According to a second aspect of the present invention, a starch-based medical adhesive is provided, characterized in that the starch-based medical adhesive is prepared by the above-mentioned method for preparing the starch-based medical adhesive.

[0030] According to a third aspect of the present invention, a starch-based medical adhesive is provided for use in preparing wound closure-related materials.

[0031] The present invention has the following advantages:

[0032] The medical adhesive of the present invention has good biocompatibility, is degradable in vivo and the degradation products are non-toxic and harmless, has strong wet tissue adhesion strength and good tissue compliance, is simple to process, can be directly applied to skin wounds, deep wounds and wounds in areas that are difficult to reach by surgery, and is simple and convenient to use.

[0033] The present invention gelatinizes two modified starches, destroying the microcrystalline regions in the modified starch structure. The presence of the microcrystalline regions limits the solubility of the modified starch and the exposure of active groups. The modified starch molecular chains after gelatinization extend, exposing more active groups and enhancing the diffusion capacity of the molecular chains. Compared with the method of directly mixing the two modified starches, the starch-based medical adhesive in the present invention has a fluffy structure, which increases the hygroscopicity and adhesion of the adhesive. The cross-linking method of the two modified starches after gelatinization is through positive and negative electrostatic interaction, that is, physical cross-linking, which gives the material good self-healing and dynamic adaptability. That is, the starch-based medical adhesive of the present invention can act directly on the wound site, quickly absorb tissue exudate, solidify in situ, and form a stable and strong adhesion, thereby achieving rapid wound closure. After use, it forms a strong adhesion to the tissue, is not easy to peel, adapts to the dynamic movement of the tissue, and is suitable for closing wounds in dynamically moving areas. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the embodiments or the description of the prior art. Obviously, the drawings described below are merely exemplary, and those skilled in the art can derive other implementation drawings based on the provided drawings without inventive effort.

[0035] The structures, proportions, sizes, etc. illustrated in this specification are intended only to complement the contents disclosed herein and to facilitate understanding and reading by persons familiar with the art. They are not intended to limit the conditions under which the present invention may be implemented and therefore have no substantive technical significance. Any structural modifications, changes in proportions, or adjustments in sizes, without affecting the efficacy and objectives of the present invention, shall still fall within the scope of the technical contents disclosed herein.

[0036] Figure 1 This is a tensile test diagram of the starch-based medical adhesive 1 after bonding provided in Experimental Example 4 of the present invention;

[0037] Figure 2 This is a test chart of tissue compliance after bonding using the starch-based medical adhesive 2 provided in Experimental Example 4 of the present invention;

[0038] Figure 3 This is a scanning electron micrograph of the cross-linked structure of the starch-based medical adhesive 5 provided in Experimental Example 4 of the present invention;

[0039] Figure 4 This is a picture of the starch-based medical adhesive 3 provided in Experimental Example 4 of the present invention after bonding to the back skin of a rat;

[0040] Figure 5 This is a diagram showing the cytotoxicity experiment of starch-based medical adhesive 4 provided in Experimental Example 4 of the present invention;

[0041] Figure 6 This is a bursting pressure test diagram of the starch-based medical adhesive 5 obtained in Experimental Example 5 provided in Experimental Example 4 of the present invention and the non-gelatinized starch-based medical adhesive 1 obtained in Comparative Example 1, wherein CMS / QS represents starch-based medical adhesive 5 and CMS / QS-Mix represents non-gelatinized starch-based medical adhesive 1. DETAILED DESCRIPTION

[0042] The following describes the implementation of the present invention using specific embodiments. Those skilled in the art will readily understand the other advantages and benefits of the present invention from the disclosure herein. Obviously, the embodiments described are only a portion of the present invention, not all of it. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0043] Example 1

[0044] This embodiment provides a method for preparing a starch-based medical adhesive:

[0045] Quaternary ammonium salt-modified corn starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyltrimethylammonium chloride was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of corn starch was evenly dispersed in 100 mL of deionized water. The NaOH / EPTAC mixture was added dropwise at a constant rate, and the mixture was reacted at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the quaternary ammonium salt-modified corn starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0046] Carboxymethyl-modified corn starch: Add 3 g of NaOH to 8 mL of deionized water, stir to dissolve, then add 100 mL of isopropanol. Stir and heat to 40°C. Subsequently, add 7.5 g of corn starch and purge with nitrogen. Stir for 1 hour, then add 7.5 g of sodium chloroacetate and allow to react for 3 hours. After the reaction, filter the resulting slurry, and wash the product five times with 85% ethanol. Wash with anhydrous ethanol, filter, and dry to obtain a carboxymethyl-modified starch powder sample.

[0047] S1, weigh 1 g of quaternary ammonium salt-modified corn starch and add it to 100 mL of deionized water. Stir magnetically at 800 rpm in a 60 °C oil bath for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution;

[0048] S2, weigh 5 g of carboxymethyl-modified corn starch and add it to 500 mL of deionized water. Stir the mixture in an oil bath at 60 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0049] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0050] S4, the modified starch complex was stirred evenly and frozen in a -20 ℃ refrigerator for 12 h;

[0051] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 48 h until the modified starch complex is completely dry;

[0052] S6. Grind the freeze-dried modified starch complex in a grinder for 10 min, and repeat the grinding 5 times to obtain a starch-based medical adhesive 1.

[0053] Example 2

[0054] This embodiment provides a method for preparing a starch-based medical adhesive:

[0055] Corn starch modified with quaternary ammonium salt: same as in Example 1.

[0056] Carboxyethyl-modified corn starch: Add 3 g of NaOH to 20 mL of deionized water, stir to dissolve, then add 100 mL of isopropanol. Stir and heat to 40°C. Subsequently, add 5 g of corn starch and purge with nitrogen. Stir for 1 hour, then add 7.5 g of ethylene oxide and allow to react for 3 hours. After the reaction, filter the resulting slurry, and wash the product five times with 85% ethanol. Wash with anhydrous ethanol, filter, and dry to obtain a carboxyethyl-modified corn starch powder.

[0057] S1, weigh 2 g of quaternary ammonium salt-modified corn starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 200 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0058] S2, weigh 8 g of carboxyethyl-modified corn starch and add it to 400 mL of deionized water. Stir the mixture in an oil bath at 200 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0059] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 20 min until the complex is uniform, to obtain a modified starch complex;

[0060] S4, the modified starch complex was stirred evenly and frozen in a -20 ℃ refrigerator for 24 h;

[0061] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 48 h until the modified starch complex is completely dry;

[0062] S6. Grind the freeze-dried modified starch complex in a grinder for 10 min, and repeat the grinding 5 times to obtain starch-based medical adhesive 2.

[0063] Example 3

[0064] This embodiment provides a method for preparing a starch-based medical adhesive:

[0065] Corn starch modified with quaternary ammonium salt: same as in Example 1.

[0066] Carboxypropyl-modified corn starch: 3 g of NaOH was added to 20 mL of deionized water and stirred to dissolve. Then, 100 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 5 g of corn starch was added and nitrogen was introduced. After stirring for 1 hour, 10 g of propylene oxide was added and the reaction was allowed to proceed for 3 hours. After completion of the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a carboxypropyl-modified corn starch powder sample.

[0067] S1, weigh 3 g of quaternary ammonium salt-modified corn starch and add it to 100 mL of deionized water. Stir the mixture in an 80 °C oil bath at 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0068] S2, weigh 9 g of carboxypropyl-modified corn starch and add it to 300 mL of deionized water. Stir the mixture in an 80°C oil bath at 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0069] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 20 min until the complex is uniform, to obtain a modified starch complex;

[0070] S4, the modified starch complex was stirred evenly and frozen in a -20 ℃ refrigerator for 60 h;

[0071] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 48 h until the modified starch complex is completely dry;

[0072] S6. Grind the freeze-dried modified starch complex in a grinder for 10 min, and repeat the grinding 5 times to obtain starch-based medical adhesive 3.

[0073] Example 4

[0074] This embodiment provides a method for preparing a starch-based medical adhesive:

[0075] Corn starch modified with quaternary ammonium salt: same as in Example 1.

[0076] Phosphate-modified corn starch: 2 g of NaOH was added to 80 mL of deionized water and stirred to dissolve. Then, 20 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 3 g of corn starch was added and nitrogen was purged. After stirring for 1 hour, 7.5 g of phosphate was added and the mixture was allowed to react for 3 hours. After completion of the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a phosphate-modified corn starch powder sample.

[0077] S1, weigh 4 g of quaternary ammonium salt-modified corn starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 220 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0078] S2, weigh 8 g of phosphate-modified corn starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 220 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0079] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 20 min until the complex is uniform, to obtain a modified starch complex;

[0080] S4, the modified starch complex was stirred evenly and frozen in a -40 ℃ refrigerator for 12 h;

[0081] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 48 h until the modified starch complex is completely dry;

[0082] S6. Grind the freeze-dried modified starch complex in a grinder for 10 min, and repeat the grinding 5 times to obtain starch-based medical adhesive 4.

[0083] Example 5

[0084] This embodiment provides a method for preparing a starch-based medical adhesive:

[0085] Tertiary amino group-modified corn starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyl-N,N-dialkylamine was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of corn starch was evenly dispersed in 100 mL of deionized water. The NaOH / DAEPA mixture was added dropwise at a constant rate, and the mixture was reacted at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the tertiary amino group-modified corn starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0086] Citrate-modified corn starch: 1 g of NaOH was added to 80 mL of deionized water and stirred to dissolve. Then, 20 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 7.5 g of corn starch was added and nitrogen was purged. After stirring for 1 hour, 4.5 g of citrate was added and the mixture was allowed to react for 3 hours. After completion of the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a citrate-modified corn starch powder sample.

[0087] S1, weigh 5 g of tertiary amino-modified corn starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 100 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0088] S2, weigh 5 g of citrate-modified corn starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 100 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0089] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0090] S4, the modified starch complex was stirred evenly and frozen in a -40 ℃ refrigerator for 24 h;

[0091] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 48 h until the modified starch complex is completely dry;

[0092] S6, grinding the freeze-dried modified starch complex in a grinder for 10 min, repeating the grinding 5 times to obtain starch-based medical adhesive 5.

[0093] Example 6

[0094] This embodiment provides a method for preparing a starch-based medical adhesive:

[0095] Tertiary amino-modified potato starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyl-N,N-dialkylamine was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of potato starch was evenly dispersed in 100 mL of deionized water. The NaOH / DAEPA mixture was added dropwise at a constant rate, and the reaction was carried out at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the tertiary amino-modified potato starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0096] Xanthate-modified potato starch: 3 g of NaOH was added to 50 mL of deionized water and stirred to dissolve. Then, 50 mL of isopropanol was added and the mixture was stirred and heated to 40°C. Subsequently, 5 g of potato starch was added and nitrogen was purged. After stirring for 1 hour, 7.5 g of xanthate was added and the reaction was allowed to proceed for 3 hours. After the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a xanthate-modified potato starch powder sample.

[0097] S1: 12 g of potato starch modified with tertiary amino groups was weighed and added to 200 mL of deionized water. The mixture was stirred magnetically at 800 rpm in an oil bath at 240 °C for 3 h until the modified starch was completely gelatinized to obtain modified starch 1 solution.

[0098] S2, weigh 6 g of xanthate-modified potato starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 240 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0099] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0100] S4, the modified starch complex was stirred evenly and frozen in a -40 ℃ refrigerator for 48 h;

[0101] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0102] S6, grinding the freeze-dried modified starch complex in a grinder for 10 min, repeating the grinding 5 times to obtain starch-based medical adhesive 6.

[0103] Example 7

[0104] This embodiment provides a method for preparing a starch-based medical adhesive:

[0105] Tertiary amino-modified potato starch: same as Example 6.

[0106] Acetate-modified potato starch: Add 0.1 g of NaOH to 90 mL of deionized water, stir to dissolve, then add 10 mL of isopropanol. Stir and heat to 40°C. Subsequently, add 5 g of potato starch and purge with nitrogen. Stir for 1 hour, then add 7.5 g of acetic anhydride and react for 3 hours. After the reaction, filter the resulting slurry, and wash the product five times with 85% ethanol. Wash with anhydrous ethanol, filter, and dry to obtain an acetate-modified potato starch powder sample.

[0107] S1, weigh 21 g of potato starch modified with tertiary amino groups and add it to 300 mL of deionized water. Stir the mixture in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0108] S2, weigh 7 g of acetate-modified potato starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0109] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0110] S4, the modified starch complex was stirred evenly and frozen in a -40 ℃ refrigerator for 60 h;

[0111] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0112] S6, grinding the freeze-dried modified starch complex in a grinder for 10 min, repeating the grinding 5 times to obtain starch-based medical adhesive 7.

[0113] Example 8

[0114] This embodiment provides a method for preparing a starch-based medical adhesive:

[0115] Tertiary amino-modified potato starch: same as Example 6.

[0116] Carboxymethylated potato starch: 3 g of NaOH was added to 8 mL of deionized water and stirred to dissolve. Then, 100 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 7.5 g of potato starch was added and nitrogen was purged. After stirring for 1 hour, 7.5 g of sodium chloroacetate was added and the reaction was allowed to proceed for 3 hours. After completion of the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a carboxymethylated potato starch powder sample.

[0117] S1, weigh 32 g of potato starch modified with tertiary amino groups and add it to 400 mL of deionized water. Stir the mixture in an oil bath at 260 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0118] S2, weigh 8 g of carboxymethylated potato starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 260 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0119] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0120] S4, the modified starch complex was stirred evenly and frozen in a -80 ℃ refrigerator for 12 h;

[0121] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0122] S6, grinding the freeze-dried modified starch complex in a grinder for 10 min, repeating the grinding 5 times to obtain a starch-based medical adhesive 8.

[0123] Example 9

[0124] This embodiment provides a method for preparing a starch-based medical adhesive:

[0125] Tertiary amino-modified potato starch: same as Example 6.

[0126] Carboxyethyl-modified potato starch: 3 g of NaOH was added to 20 mL of deionized water and stirred to dissolve. Then, 100 mL of isopropanol was added and the mixture was stirred and heated to 40°C. Subsequently, 5 g of potato starch was added and nitrogen was bubbled through the mixture. After stirring for 1 hour, 7.5 g of ethylene oxide was added and the reaction was allowed to proceed for 3 hours. After the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a carboxyethyl-modified potato starch powder sample.

[0127] S1, weigh 45 g of potato starch modified with tertiary amino groups and add it to 500 mL of deionized water. Stir the mixture in an oil bath at 140 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0128] S2, weigh 9 g of carboxyethyl-modified potato starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 140 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0129] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm for 20 min until the complex is uniform, thereby obtaining a modified starch complex;

[0130] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 24 h;

[0131] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0132] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 9.

[0133] Example 10

[0134] This embodiment provides a method for preparing a starch-based medical adhesive:

[0135] Tertiary amino group-modified wheat starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyl-N,N-dialkylamine was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of wheat starch was evenly dispersed in 100 mL of deionized water. The NaOH / DAEPA mixture was added dropwise at a constant rate, and the mixture was reacted at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the tertiary amino group-modified wheat starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0136] Carboxypropyl-modified wheat starch: 3 g of NaOH was added to 20 mL of deionized water and stirred to dissolve. Then, 100 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 5 g of wheat starch was added and nitrogen was introduced. After stirring for 1 hour, 10 g of propylene oxide was added and the reaction was allowed to proceed for 3 hours. After the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a carboxypropyl-modified wheat starch powder sample.

[0137] S1, weigh 5 g of wheat starch modified with tertiary amino groups and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 280 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0138] S2, weigh 10 g of carboxypropyl-modified wheat starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 280 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0139] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0140] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0141] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0142] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 10.

[0143] Example 11

[0144] This embodiment provides a method for preparing a starch-based medical adhesive:

[0145] Quaternary ammonium salt-modified soybean starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyltrimethylammonium chloride was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of soybean starch was evenly dispersed in 100 mL of deionized water. The NaOH / EPTAC mixture was added dropwise at a constant rate, and the mixture was reacted at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the quaternary ammonium salt-modified soybean starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0146] Carboxyethyl-modified soybean starch: Add 3 g of NaOH to 20 mL of deionized water, stir to dissolve, then add 100 mL of isopropanol. Stir and heat to 40°C. Subsequently, add 5 g of soybean starch and purge with nitrogen. Stir for 1 hour, then add 7.5 g of ethylene oxide and allow to react for 3 hours. After the reaction, filter the resulting slurry, and wash the product five times with 85% ethanol. Wash with anhydrous ethanol, filter, and dry to obtain a carboxyethyl-modified soybean starch powder sample.

[0147] S1, weigh 5 g of quaternary ammonium salt-modified soybean starch and add it to 100 mL of deionized water. Stir the mixture in an oil bath at 160 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0148] S2, weigh 10 g of carboxyethyl-modified soybean starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 160 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0149] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0150] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0151] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0152] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 11.

[0153] Example 12

[0154] This embodiment provides a method for preparing a starch-based medical adhesive:

[0155] Quaternary ammonium salt-modified lotus root starch: First, 0.9 g of sodium hydroxide was dissolved in 5 mL of deionized water and magnetically stirred until the solution was clear. Simultaneously, 3 g of 2,3-epoxypropyltrimethylammonium chloride was dispersed in 20 mL of deionized water and stirred until completely dissolved. The two solutions were then mixed and thoroughly homogenized. Next, 3 g of lotus root starch was evenly dispersed in 100 mL of deionized water. The NaOH / EPTAC mixture was added dropwise at a constant rate, and the mixture was reacted at 40°C for 24 h to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the quaternary ammonium salt-modified lotus root starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0156] Carboxymethyl-modified lotus root starch: 3 g of NaOH was added to 8 mL of deionized water and stirred to dissolve. Then, 100 mL of isopropanol was added, stirred, and heated to 40°C. Subsequently, 7.5 g of lotus root starch was added and nitrogen was introduced. After stirring for 1 hour, 7.5 g of sodium chloroacetate was added and the mixture was allowed to react for 3 hours. After the reaction, the resulting slurry was filtered, and the product was washed five times with 85% ethanol. The product was then washed with anhydrous ethanol, filtered, and dried to obtain a carboxymethyl-modified lotus root starch powder sample.

[0157] S1, weigh 2 g of quaternary ammonium salt-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0158] S2, weigh 2 g of carboxymethyl-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0159] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0160] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0161] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0162] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 12.

[0163] Example 13

[0164] This embodiment provides a method for preparing a starch-based medical adhesive:

[0165] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0166] S1, weigh 0.2 g of quaternary ammonium salt-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0167] S2, weigh 1.8 g of carboxymethyl-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0168] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0169] S4, quenching the uniformly stirred modified starch complex in liquid nitrogen for 1 h;

[0170] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0171] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 13.

[0172] Example 14

[0173] This embodiment provides a method for preparing a starch-based medical adhesive:

[0174] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0175] S1, weigh 1 g of quaternary ammonium salt-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0176] S2, weigh 8 g of carboxymethyl-modified lotus root starch and add it to 400 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0177] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0178] S4, quenching the uniformly stirred modified starch complex in liquid nitrogen for 2 h;

[0179] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0180] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive 14.

[0181] Example 15

[0182] This embodiment provides a method for preparing a starch-based medical adhesive:

[0183] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0184] S1, weigh 7 g of quaternary ammonium salt-modified lotus root starch and add it to 350 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0185] S2, weigh 1 g of carboxymethyl-modified lotus root starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 300 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0186] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0187] S4, quenching the uniformly stirred modified starch complex in liquid nitrogen for 3 h;

[0188] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0189] S6, grinding the freeze-dried modified starch complex in a grinder for 10 min, repeating the grinding 5 times to obtain a starch-based medical adhesive 15.

[0190] Comparative Example 1

[0191] This comparative example provides a method for preparing a starch-based medical adhesive:

[0192] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0193] S1, weigh 0.1 g of quaternary ammonium salt-modified lotus root starch and add it to 200 mL of deionized water. Stir magnetically in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution;

[0194] S2, weigh 0.8 g of carboxymethyl-modified lotus root starch and add it to 400 mL of deionized water. Stir magnetically in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution;

[0195] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0196] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0197] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0198] S6. Grind the freeze-dried modified starch complex in a grinder for 10 minutes, and repeat the grinding 5 times to obtain a low-concentration starch-based medical adhesive 1.

[0199] Comparative Example 2

[0200] This comparative example provides a method for preparing a starch-based medical adhesive:

[0201] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0202] S1, weigh 50 g of quaternary ammonium salt-modified lotus root starch and add it to 100 mL of deionized water. Stir magnetically in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution;

[0203] S2, weigh 100 g of carboxymethyl-modified lotus root starch and add it to 200 mL of deionized water. Stir magnetically at 800 rpm in an oil bath at 120 °C for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution;

[0204] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0205] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0206] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0207] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a high-concentration starch-based medical adhesive 1.

[0208] Comparative Example 3

[0209] This comparative example provides a method for preparing a starch-based medical adhesive:

[0210] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0211] S1, weigh 0.05 g of quaternary ammonium salt-modified lotus root starch and add it to 1 mL of deionized water. Stir magnetically at 800 rpm in an oil bath at 120 °C for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution;

[0212] S2, weigh 10 g of carboxymethyl-modified lotus root starch and add it to 200 mL of deionized water. Stir magnetically at 800 rpm in an oil bath at 120 °C for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution;

[0213] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0214] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0215] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0216] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a low-ratio starch-based medical adhesive 1.

[0217] Comparative Example 4

[0218] This comparative example provides a method for preparing a starch-based medical adhesive:

[0219] Lotus root starch modified with quaternary ammonium salt: same as in Example 12. Lotus root starch modified with carboxymethyl: same as in Example 12.

[0220] S1, weigh 15 g of quaternary ammonium salt-modified lotus root starch and add it to 300 mL of deionized water. Stir the mixture in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 1 solution.

[0221] S2, weigh 0.1 g of carboxymethyl-modified lotus root starch and add it to 2 mL of deionized water. Stir magnetically in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0222] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0223] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0224] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0225] S6. Grind the freeze-dried modified starch complex in a grinder for 10 minutes, and repeat the grinding 5 times to obtain a low-ratio starch-based medical adhesive 2.

[0226] Comparative Example 5

[0227] This comparative example provides a method for preparing a starch-based medical adhesive:

[0228] The potato starch modified with tertiary amino groups and the potato starch modified with acetate are the same as those in Example 7.

[0229] S1, weigh 2 g of tertiary amino-modified potato starch and 2 g of acetate-modified potato starch;

[0230] S2, the two modified starches were pulverized in a pulverizer for 10 min respectively;

[0231] S3, mixing the two crushed modified starches to obtain a non-gelatinized starch-based medical adhesive 1.

[0232] Comparative Example 6

[0233] This comparative example provides a method for preparing a starch-based medical adhesive:

[0234] The quaternary ammonium salt-modified corn starch and the carboxymethyl-modified corn starch are the same as those in Example 1.

[0235] S1, weigh 2 g of quaternary ammonium salt-modified corn starch and 4 g of carboxymethyl-modified corn starch;

[0236] S2, the two modified starches were pulverized in a pulverizer for 10 min respectively;

[0237] S3, mixing the two crushed modified starches to obtain non-gelatinized starch-based medical adhesive 2.

[0238] Comparative Example 7

[0239] This comparative example provides a method for preparing a starch-based medical adhesive:

[0240] The corn starch modified with quaternary ammonium salt is the same as that in Example 1.

[0241] S1, weigh 10 g of quaternary ammonium salt-modified corn starch;

[0242] S2, add the modified starch to 500 mL of deionized water and stir magnetically at 800 rpm in an oil bath at 300 °C for 3 h until the modified starch is completely gelatinized;

[0243] S3, gelatinized modified starch was frozen at -80 °C for 48 h;

[0244] S4, freeze-drying the frozen modified starch in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0245] S5, grinding the freeze-dried modified starch in a grinder for 10 min, repeating the grinding 5 times to obtain a single-component starch-based medical adhesive 1.

[0246] Comparative Example 8

[0247] This comparative example provides a method for preparing a starch-based medical adhesive:

[0248] The carboxymethylated corn starch is the same as that in Example 1.

[0249] S1, weigh 10 g of carboxymethyl-modified corn starch;

[0250] S2, add the modified starch to 500 mL of deionized water and stir magnetically at 800 rpm in an oil bath at 300 °C for 3 h until the modified starch is completely gelatinized;

[0251] S3, gelatinized modified starch was frozen at -80 °C for 48 h;

[0252] S4, freeze-drying the frozen modified starch in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0253] S5, grinding the freeze-dried modified starch in a grinder for 10 min, repeating the grinding 5 times to obtain a single-component starch-based medical adhesive 2.

[0254] Comparative Example 9

[0255] This comparative example provides a method for preparing a starch-based medical adhesive:

[0256] Decylamine-modified corn starch: 4 g of corn starch was evenly dispersed in 200 mL of deionized water. 1 mL of epichlorohydrin and 3 mL of N,N-dimethyldecylamine were added and the mixture was allowed to react at 40°C for 24 hours to complete the grafting modification. After the reaction, the crude product was dialyzed against deionized water for 3 days (changing the water 3-4 times daily) to remove unreacted small molecular impurities. Finally, the decylamine-modified corn starch powder sample was obtained by freeze-drying, pulverization, and sieving.

[0257] The carboxymethyl-modified corn starch is the same as that in Example 1.

[0258] S1, weigh 1 g of decylamine-modified corn starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 3 solution.

[0259] S2, weigh 2 g of carboxymethyl-modified corn starch and add it to 200 mL of deionized water. Stir the mixture in an oil bath at 120 °C and 800 rpm for 3 h until the modified starch is completely gelatinized to obtain modified starch 2 solution.

[0260] S3, mixing the completely gelatinized modified starch 1 solution and the modified starch 2 solution under magnetic stirring at 800 rpm, and stirring for 15 min until the complex is uniform, to obtain a modified starch complex;

[0261] S4, the uniformly stirred modified starch complex was frozen in a -80 ℃ refrigerator for 48 h;

[0262] S5, freeze-drying the frozen modified starch complex in a freeze dryer for 72 h until the modified starch complex is completely dry;

[0263] S6, grinding the freeze-dried modified starch complex in a grinder for 10 minutes, repeating the grinding 5 times to obtain a starch-based medical adhesive.

[0264] Experimental Example 1

[0265] The medical adhesives prepared in Examples 1-15 and Comparative Examples 1-9 were used as test objects to test their tissue peeling strength and adhesion time. The test method was as follows: the test sample was applied between two pieces of fresh pig skin with a contact area of ​​1×2.5 cm 2 The bonded pigskin was lifted every 2 seconds and a 50g weight was suspended from one end. The tissue bonding time was recorded when the two pieces of pigskin were completely bonded without sliding and could withstand the 50g weight. After 5 minutes of bonding, the tissue peel force was recorded in a tensile tester to obtain the data in Table 1.

[0266] Table 1 Adhesion time and adhesion strength of medical adhesive on pig skin tissue

[0267]

[0268] Adhesion strength and adhesion time are the core properties of a medical adhesive, which determine whether the medical adhesive can provide timely and stable adhesion effects during use.

[0269] From the comparison of the data in Table 1, it can be seen that: in Comparative Examples 1 and 2, the concentration of the modified starch solution is too low or too high, which easily leads to difficulty in fully cross-linking the two modified starch solutions when mixed, resulting in too weak strength of the adhesive body and difficulty in forming effective adhesion on the tissue; in Comparative Examples 3 and 4, the mass ratio of the two modified starches is too high or too low, resulting in a serious excess of a certain group, insufficient cross-linking density, too weak strength of the adhesive body, and difficulty in forming effective adhesion on the tissue; Comparative Examples 5 and 6 are simple mixtures of two modified starches that have not been gelatinized. Due to the limitation of the crystal structure, the modified starch particles can only swell to a certain extent after contacting the interfacial water on the tissue, the diffusion of the molecular chain is restricted, the adhesion group cannot be exposed, and only the groups on the surface of the particles participate in the adhesion, resulting in insufficient adhesion strength; Comparative Examples 7 and 8 are single-component modified starches, whose molecular structure is too low. Although there are sufficient adhesion groups in the structure, the intermolecular force is weak, and it is difficult to form effective cross-linking. The strength of the adhesive body is too weak, and it is difficult to form effective adhesion on the tissue; the starch modified with decylamine in Comparative Example 9 has a long alkane chain due to the decylamine group, which is highly hydrophobic, affecting the solubility of the material and the binding with the tissue interface, resulting in insufficient adhesion strength; Examples 1-15 are all composites obtained by freeze-drying after high-temperature gelatinization of two modified starches carrying positive and negative groups. The large number of adhesion groups carried on the modified starch molecular chains can form hydrogen bonds with the tissue interface and electrostatic effects between positive and negative ions. The gelatinization process enhances the diffusion of molecular chains, allowing the molecular chains to diffuse rapidly into the tissue gaps, forming a mechanical interlocking effect after solidification. The multi-level adhesion network greatly improves its adhesion strength compared with Comparative Examples 1-9.

[0270] Experimental Example 2

[0271] The medical adhesives prepared in Examples 1-15 and Comparative Examples 1-9 were used as test objects to test their post-gel strength. The test method was as follows: the test sample was prepared into a gel with a PBS solution at a solid content of 10%. A stress-controlled rotational rheometer (model: HR-1, manufacturer: TA Instrument) was used to measure the rheological properties of the hydrogel. The test plate had a 20 mm test plate. The storage modulus and loss modulus were measured at a strain of 1%. Whether the storage modulus was greater than the loss modulus was used to determine whether the hydrogel was an elastic solid. The maximum deformation was measured at a frequency of 1 Hz.

[0272] Table 2 Rheological tests of medical adhesives

[0273]

[0274] Powdered medical adhesives should be able to absorb water at the tissue interface and solidify to form a colloid with a certain mechanical strength, providing an effective physical barrier for the wound tissue.

[0275] As can be seen from Table 2: the modified starch solution concentrations in Comparative Examples 1 and 2 are too low or too high, which easily leads to difficulty in fully cross-linking when the two modified starch solutions are mixed, resulting in too weak strength of the adhesive body, which is likely to break under the action of tissue deformation and cannot form an effective physical barrier; the mass ratio of the two modified starches in Comparative Examples 3 and 4 is too high or too low, resulting in a serious excess of a certain group, insufficient cross-linking density, too weak strength of the adhesive body, which is likely to break under the action of tissue deformation and cannot form an effective physical barrier; Comparative Examples 5 and 6 are simple mixtures of two modified starches that have not been gelatinized. Due to the limitation of the crystalline structure, the modified starch particles can only swell to a certain extent after contacting the interfacial water on the tissue, the diffusion of the molecular chains is restricted, a large number of active groups cannot be exposed, and only the groups on the surface of the particles participate in the cross-linking, resulting in insufficient cross-linking strength. Although they can form The present invention has a colloidal structure, but the colloidal strength is low, and it is likely to break under the action of tissue deformation, and cannot form an effective physical barrier; Comparative Examples 7 and 8 are medical adhesives prepared from single-component modified starch, and the cross-linking effect between molecules is insufficient. After absorbing interfacial water, a colloidal structure cannot be formed, and a physical barrier cannot be formed; the starch modified with decylamine in Comparative Example 9 has a long alkane chain due to the decylamine group, and is highly hydrophobic, and is prone to agglomeration in water, resulting in insufficient cross-linking density; Examples 1-15 are all composites obtained by high-temperature gelatinization and then freeze-drying of two modified starches carrying positive and negative groups. The large number of active groups carried on the modified starch molecular chains can form hydrogen bonds between molecular chains and electrostatic effects between positive and negative ions. The cross-linking degree is high, and the colloid strength formed is much higher than that of Comparative Examples 1-8, and an effective physical barrier can be formed even under the action of tissue deformation.

[0276] Experimental Example 3

[0277] The medical adhesives prepared in Examples 1-15 and Comparative Examples 1-9 were used as test objects to test their liquid absorption capacity. The test method was as follows: 50 mg of the test sample was weighed and immersed in a PBS solution. The test sample was removed every 1 min, excess water on the surface of the sample was absorbed with filter paper, and its mass was weighed. The maximum absorption time was 20 min, and the sample absorption rate and the absorption ratio at the 20-min time point were calculated.

[0278] Table 3 Liquid absorption rate and liquid absorption ratio test of medical adhesives

[0279]

[0280] Interfacial water is one of the main factors affecting the adhesion of medical adhesives to tissues. Powdered medical adhesives can absorb interfacial water from tissues, weakening or eliminating the effect of interfacial water on the adhesion properties of materials. Therefore, good liquid absorption capacity is the core performance of powdered medical adhesives.

[0281] As can be seen from Table 3: the modified starch solution concentrations of Comparative Examples 1 and 2 are too low or too high, which easily leads to insufficient crosslinking when the two modified starch solutions are mixed, resulting in too weak adhesive bulk strength, easy colloid disintegration when absorbing liquid, and limited liquid absorption capacity; the mass ratio of the two modified starches in Comparative Examples 3 and 4 is too high or too low, resulting in a serious excess of a certain group, insufficient crosslinking density, too weak adhesive bulk strength, easy colloid disintegration when absorbing liquid, and limited liquid absorption capacity; Comparative Examples 5 and 6 are simple mixtures of two modified starches that have not been gelatinized. Due to the limitations of the crystal structure, the modified starch particles can only swell to a certain extent after contacting the interfacial water on the tissue, and the liquid absorption capacity is limited; Comparative Examples 7 and 8 are medical adhesives prepared from single-component modified starch, and the intermolecular crosslinking effect is insufficient. The gelatinization process destroys the restriction of the crystal structure on the diffusion of molecular chains, making it impossible for the samples to absorb tissue interfacial water when dissolved in PBS solution;

[0282] The decylamine-modified starch in Comparative Example 9 has a long alkane chain due to the decylamine group and is highly hydrophobic. When the material comes into contact with tissue, it will repel water molecules and its liquid absorption capacity will be greatly reduced. Examples 1-15 are all composites obtained by freeze-drying two modified starches after high-temperature gelatinization. The gelatinization process exposes a large number of hydrophilic groups on the modified starch molecular chains, which absorb water through hydration, and its liquid absorption capacity is greatly improved compared with Comparative Examples 1-9.

[0283] Experimental Example 4

[0284] This experimental example tests the performance of starch-based medical adhesives prepared in different embodiments:

[0285] The tensile strength of the starch-based medical adhesive 1 obtained in Example 1 after bonding was tested, and the results were as follows: Figure 1 As shown, from Figure 1 It can be seen that starch-based medical adhesive can withstand a tensile force of 1 kg, can be used for stretched wounds, and can achieve effective closure.

[0286] The tissue compliance of the starch-based medical adhesive 2 obtained in Example 2 after bonding was tested, and the results were as follows: Figure 2 As shown, from Figure 2 It can be seen that starch-based medical adhesive adheres to pig skin tissue and can withstand distortion without falling off, and can be used to close wounds in dynamic areas.

[0287] The cross-linked structure of the starch-based medical adhesive 5 obtained in Example 5 is shown in the scanning electron microscope image. Figure 3 As shown, from Figure 3 It can be seen that the starch-based medical adhesive connects linear molecules to each other to form a network structure, which improves the strength and elasticity of the adhesive.

[0288] The starch-based medical adhesive obtained in Example 3 was tested for adhesion to the back of rats. The results are as follows: Figure 4 As shown, from Figure 4 It can be seen that starch-based medical adhesives can be widely used in closing biological tissue wounds.

[0289] Adhesion test on rat back Experimental method: SPF rats weighing 250g were selected, and the back hair was removed. Surgical wounds with a length of 2cm and a depth of 5mm were sprayed with starch-based medical adhesive 3 after hemostasis for adhesion test. The adhesion was achieved in 1 minute. The rats' activities were not affected after adhesion, and no wound cracking was observed after movement.

[0290] The starch-based medical adhesive 4 obtained in Example 4 was subjected to a cytotoxicity test. Figure 5 As shown, from Figure 5 It can be seen that starch-based medical adhesives have high biological safety.

[0291] The burst pressure test of the starch-based medical adhesive 5 obtained in Experimental Example 5 and the non-gelatinized starch-based medical adhesive 1 obtained in Comparative Example 1 was conducted. The results are as follows: Figure 6 As shown, from Figure 6 It can be seen that the bursting pressure of starch-based medical adhesive is much higher than that of non-gelatinized starch-based medical adhesive.

[0292] It can be seen from this that the starch-based medical adhesive of the present invention has low cytotoxicity and high bonding strength, and does not affect the subsequent movement of rats after bonding.

[0293] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made thereto. Therefore, such modifications and improvements, without departing from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A method for preparing a starch-based medical adhesive, characterized in that: The method comprises: Step 1: Modified starch pretreatment Add modified starch 1 to water, heat and stir in an oil bath for gelatinization to obtain modified starch 1 solution; add modified starch 2 to water, heat and stir in an oil bath for gelatinization to obtain modified starch 2 solution; the concentrations of modified starch 1 solution and modified starch 2 solution are both 0.1%-10%; Step 2: Mix The modified starch 1 solution and the modified starch 2 solution are mixed and stirred evenly to obtain a modified starch complex; the mass ratio of the modified starch 1 solution to the modified starch 2 solution is 0.1-0.9:0.9-0.1; Step 3: Freezing, drying and crushing The modified starch complex is first subjected to low-temperature freezing treatment, and then freeze-dried, and the freeze-dried modified starch complex is crushed to obtain a starch-based medical adhesive; Wherein, the modified starch 1 is one or more of carboxymethyl-modified starch, carboxyethyl-modified starch, carboxypropyl-modified starch, phosphate-modified starch, xanthate-modified starch, citrate-modified starch, acetate-modified starch, and acetylated diphosphate-modified starch; The modified starch 2 is starch modified with a quaternary ammonium salt and / or starch modified with a tertiary aminoalkyl group.

2. The method for preparing a starch-based medical adhesive according to claim 1, characterized in that: The starch is one or more of bean starch, potato starch, cereal starch, water chestnut starch, and lotus root starch.

3. The method for preparing a starch-based medical adhesive according to claim 1, characterized in that: In the step 1, the heating temperature is 40-300°C.

4. The method for preparing a starch-based medical adhesive according to claim 1, characterized in that: In the step 3, the temperature of the cryogenic freezing is -10 to -270°C.

5. A starch-based medical adhesive, characterized in that: The starch-based medical adhesive is prepared by the preparation method of the starch-based medical adhesive according to any one of claims 1-4.

6. Use of the starch-based medical adhesive according to claim 5 in preparing wound closure related materials.

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