Porous starch microsphere styptic powder and preparation method thereof

Abstract

The invention discloses porous starch microsphere styptic powder and a preparation method thereof, and belongs to the field of biological medicine. Starch is prepared into porous starch in an ultrasonic mode, the porous starch is carboxymethylated into sodium carboxymethyl starch, collagen and carboxymethyl starch are prepared into water-in-water emulsion by using an emulsion suspension polymerization technology, protein-crosslinked starch microspheres are obtained after vacuum drying, the starch microspheres are crosslinked by using a crosslinking agent, and the starch microspheres are prepared into the collagen / carboxymethyl starch composite material. And drying in vacuum to obtain the porous starch microsphere styptic powder. The prepared porous starch microsphere styptic powder is rough in surface, multiple in pores and large in specific surface area and specific pore volume, the crosslinked structure enables the styptic powder to have high water absorption speed and high water absorption rate, collagen wrapping can prolong the existence time of the styptic powder and improve the heat-resistant effect of the styptic powder, and meanwhile collagen and starch can be automatically degraded in a living body. The product has the advantages of strong hemostatic effect, high heat-resistant effect, capability of naturally degrading in a living body and the like, and can be used for hemostasis of injured tissues or blood vessels.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to porous starch microsphere hemostatic powder and a preparation method thereof. Background Art

[0002] When a person or animal is injured, especially in emergency situations such as traffic accidents, engineering accidents, and natural disasters, if the body cannot stop bleeding on its own, hemostatic materials are needed. Hemostatic powder is a commonly used hemostatic material. Usually, hemostatic powder needs to meet the requirements of high hemostatic properties and high water absorption. At the same time, since hemostatic powder is used on the wound surface or tissue surface of humans or animals for hemostasis, it also needs to have good biocompatibility. The "Arista" absorbable starch hemostatic microspheres produced by Medafor in the United States have good safety and good hemostatic effects, but the product is expensive and as an in vivo hemostatic material, its adhesion and liquid absorption are not strong enough, especially the epichlorohydrin cross-linking agent may have potential toxicity.

[0003] Chinese patent CN102406956B discloses a method for preparing starch hemostatic microspheres, which is characterized in that the starch microspheres are prepared by a reverse suspension emulsification method. The microspheres prepared by this method have no surface porous structure and a small specific surface area. As a hemostatic material, they only have a high water absorption rate and cannot stop bleeding through the molecular sieve principle.

[0004] Chinese patent CN109498832B discloses a cross-linked porous hemostatic microsphere and its preparation method, which is characterized in that starch microspheres are prepared by reverse suspension emulsification method, and then porous microspheres are prepared by using biological enzymes. A large amount of organic phase solvent is required for reaction, and the biological enzyme reaction time is long and difficult to control.

[0005] The paper "Effect of Cross-linking Degree on the Performance of Cross-linked Carboxymethyl Starch" (Wang Jiankun, Fan Xinyu, Zhang Hao, et al. Effect of Cross-linking Degree on the Performance of Cross-linked Carboxymethyl Starch [J]. Applied Chemical Industry, 2018, 47 (04): 708-711+715) discussed the effects of the degree of cross-linking and degree of substitution of cross-linked carboxymethyl starch on the adsorption amount, and proved that under the same degree of substitution, the greater the degree of cross-linking, the greater the adsorption amount.

[0006] Compared with the disadvantages of complicated production process and long production cycle of hemostatic powder in the above-mentioned patent, the use of chemical methods to produce porous microspheres can reduce reaction time, reduce reaction energy consumption, and prepare hemostatic powder with high water absorption rate, fast water absorption rate and high biocompatibility. Summary of the invention

[0007] In order to solve the problems of low water absorption rate, small water absorption ratio and poor biocompatibility in hemostatic powder, the present invention provides a porous starch microsphere hemostatic powder and a preparation method thereof.

[0008] The invention point of the present invention is that raw materials with high biocompatibility are used to prepare hemostatic powder, the prepared product is harmless to organisms, and the operation is simple and the preparation time is short.

[0009] The present invention provides a method for preparing porous starch microsphere hemostatic powder, which is characterized by the following steps and conditions: (1) Preparation of porous starch The starch is dissolved in water, homogenized, centrifuged, the lower precipitate is removed and dried, and porous starch is obtained; (2) Preparation of sodium carboxymethyl starch The porous starch obtained in step (1) is dissolved in water, and an alkali is added to adjust the pH value and then fully reacted, and chloroacetic acid is added to the starch to continue the reaction, and the product is washed and dried to obtain sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen are dissolved in distilled water at a ratio of 0.7-1.3:1.3-0.7:8 (m / m / m), poured into a PEG solution, stirred, centrifuged, and the lower precipitate is removed and dried to obtain collagen cross-linked starch microspheres; (4) Preparation of cross-linked sodium carboxymethyl starch The product obtained in step (3) is gelatinized in water, 0.1-1.0 g of a cross-linking agent is added to the solution after being mixed evenly, and the mixture is stirred at 60-80° C. to obtain a cross-linked sodium carboxymethyl starch emulsion;

[0010] (5) Preparation of porous starch microsphere hemostatic powder The sodium carboxymethyl starch emulsion obtained in step (4) is allowed to stand for stratification, the lower layer of liquid is taken, ethanol is added and stirred, and the mixture is allowed to stand for stratification, the lower layer of solid-liquid mixture is filtered under reduced pressure, and the obtained solid is dried to obtain porous starch microsphere hemostatic powder.

[0011] Preferably, the starch in step (1) is common corn starch, potato starch, sweet potato starch, etc.

[0012] Preferably, the alkali in step (2) is one or more of sodium hydroxide, calcium hydroxide and potassium hydroxide.

[0013] Preferably, the pH value in step (2) should be greater than 8.

[0014] Preferably, the amount of chloroacetic acid added in step (2) is starch: chloroacetic acid = 0.8-1.2: 7-10 (m / m).

[0015] Preferably, the cross-linking agent in step (4) may be sodium trimetaphosphate, sodium hexametaphosphate, or the like.

[0016] Preferably, the PEG in step (5) includes PEG 300 and PEG 400.

[0017] The beneficial effects of the present invention are as follows: the preparation method can obtain a porous starch microsphere hemostatic powder with a cross-linked network structure; it has a high water absorption rate; it has a fast water absorption rate, and the starch units can be absorbed and decomposed by the human body, and it is harmless to the human body or organisms. DETAILED DESCRIPTION

[0018] The present invention is further described in detail below in conjunction with the examples, but the implementation method of the present invention is not limited thereto.

[0019] Example 1 (1) Preparation of porous starch The starch was dissolved in distilled water at a ratio of 1:9 (m / m), and ultrasonically treated with a homogenizer at a frequency of 20 kHz and a power of 170 W at 20 ° C for 30 min. The suspension was centrifuged, and the lower precipitate was taken out and transferred to a vacuum drying oven and dried at 80 ° C for 8 h. (2) Preparation of sodium carboxymethyl starch The product obtained in step (1) was dissolved in distilled water at a ratio of 1:9 (m / m), and a 2% NaOH solution was added to adjust the pH to 9. After sufficient reaction at 60° C., chloroacetic acid was added with starch at a ratio of 1:10 (m / m), and stirring was continued for 5 h. The obtained product was washed with a large amount of distilled water, and then dehydrated and washed with ethanol. After the washing, the solid-liquid mixture was separated and transferred to a Buchner funnel for vacuum filtration, and washed with ethanol continuously to remove the reaction residue. After repeating for more than three times, the mixture was transferred to a vacuum drying oven and dried at 60° C. for 10 h to obtain the product sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen were dissolved in distilled water at a ratio of 1:1:9 (m / m / m), and the resulting solution was poured into a PEG solution (40%, w / w) at a ratio of 1:5 (v / v), stirred at 300 rpm for 15 min at 50°C, allowed to stand at 4°C for 24 h, and the lower precipitate was removed after centrifugation, washed with ethanol, transferred to a vacuum drying oven, and dried at 60°C for 10 h; (4) Preparation of cross-linked sodium carboxymethyl starch The product obtained in step (3) was dissolved in distilled water at a ratio of 1:9 (m / m), and gelatinized at 30° C. for 60 min. After the solution was mixed evenly, 0.1 g of a cross-linking agent was added, and the mixture was stirred at 300 rpm for 1.0 h at 60° C. to obtain a cross-linked sodium carboxymethyl starch emulsion; (5) Preparation of porous starch microsphere hemostatic powder The emulsion obtained in step (4) was allowed to stand for stratification, and the lower layer of milky white liquid was taken. Ethanol was added at a ratio of 1:5 (v / v) and stirred. After stratification again, the lower layer of milky white solid-liquid mixture was transferred to a Buchner funnel for vacuum filtration. The filtered product was transferred to a vacuum drying oven and dried at 60°C for 10 h to obtain a white solid powder. The obtained product was porous starch microsphere hemostatic powder.

[0020] Example 2 (1) Preparation of porous starch The starch was dissolved in distilled water at a ratio of 1:9 (m / m), and ultrasonically treated with a homogenizer at 20 kHz and 170 W for 30 min at 20 °C. The suspension was centrifuged, and the lower precipitate was taken out and transferred to a vacuum drying oven and dried at 60 °C for 10 h. (2) Preparation of sodium carboxymethyl starch The product obtained in step (1) was dissolved in distilled water at a ratio of 1:9 (m / m), and a 2% NaOH solution was added to adjust the pH to 9. After sufficient reaction at 60° C., chloroacetic acid was added with starch at a ratio of 1:10 (m / m), and stirring was continued for 5 h. The obtained product was washed with a large amount of distilled water, and then dehydrated and washed with ethanol. After the washing, the solid-liquid mixture was separated and transferred to a Buchner funnel for vacuum filtration, and washed with ethanol continuously to remove the reaction residue. After repeating for more than three times, the mixture was transferred to a vacuum drying oven and dried at 60° C. for 10 h to obtain the product sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen were dissolved in distilled water at a ratio of 1:1:9 (m / m / m), and the resulting solution was poured into a PEG solution (40%, w / w) at a ratio of 1:5 (v / v), stirred at 300 rpm for 15 min at 50°C, allowed to stand at 4°C for 24 h, and the lower precipitate was removed after centrifugation, washed with ethanol, transferred to a vacuum drying oven, and dried at 60°C for 10 h; (4) Preparation of cross-linked sodium carboxymethyl starch The product obtained in step (3) was dissolved in distilled water at a ratio of 1:9 (m / m), gelatinized at 30° C. for 60 min, 0.5 g of a cross-linking agent was added after the solution was mixed evenly, and stirred at 70° C. at 300 rpm for 2.0 h to obtain a cross-linked sodium carboxymethyl starch emulsion; (5) Preparation of porous starch microsphere hemostatic powder The emulsion obtained in step (4) was allowed to stand for stratification, and the lower layer of milky white liquid was taken. Ethanol was added at a ratio of 1:5 (v / v) and stirred. After stratification again, the lower layer of milky white solid-liquid mixture was transferred to a Buchner funnel for vacuum filtration. The filtered product was transferred to a vacuum drying oven and dried at 60°C for 10 h to obtain a white solid powder. The obtained product was porous starch microsphere hemostatic powder.

[0021] Example 3 (1) Preparation of porous starch The starch was dissolved in distilled water at a ratio of 1:9 (m / m), and ultrasonically treated with a homogenizer at 20 kHz and 170 W for 30 min at 20 °C. The suspension was centrifuged, and the lower precipitate was taken out and transferred to a vacuum drying oven and dried at 60 °C for 10 h. (2) Preparation of sodium carboxymethyl starch The product obtained in step (1) was dissolved in distilled water at a ratio of 1:9 (m / m), and a 2% NaOH solution was added to adjust the pH to 9.7. After sufficient reaction at 60° C., chloroacetic acid was added with starch at a ratio of 1:10 (m / m), and stirring was continued for 5 h. The obtained product was washed with a large amount of distilled water, and then dehydrated and washed with ethanol. After washing, the solid-liquid mixture was separated and transferred to a Buchner funnel for vacuum filtration, and washed with ethanol continuously to remove the reaction residue. After repeating for more than three times, the mixture was transferred to a vacuum drying oven and dried at 60° C. for 10 h to obtain the product sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen were dissolved in distilled water at a ratio of 1:1:9 (m / m / m), and the resulting solution was poured into a PEG solution (40%, w / w) at a ratio of 1:5 (v / v), stirred at 300 rpm for 15 min at 50°C, allowed to stand at 4°C for 24 h, and the lower precipitate was removed after centrifugation, washed with ethanol, transferred to a vacuum drying oven, and dried at 60°C for 10 h; (4) Preparation of cross-linked sodium carboxymethyl starch The product obtained in step (3) was dissolved in distilled water at a ratio of 1:9 (m / m), and gelatinized at 30° C. for 60 min. After the solution was mixed evenly, 1.0 g of a cross-linking agent was added, and the mixture was stirred at 80° C. and 500 rpm for 3.5 h to obtain a cross-linked sodium carboxymethyl starch emulsion; (5) Preparation of porous starch microsphere hemostatic powder The emulsion obtained in step (4) was allowed to stand for stratification, and the lower layer of milky white liquid was taken. Ethanol was added at a ratio of 1:5 (v / v) and stirred. After stratification again, the lower layer of milky white solid-liquid mixture was transferred to a Buchner funnel for vacuum filtration. The filtered product was transferred to a vacuum drying oven and dried at 60°C for 10 h to obtain a white solid powder. The obtained product was porous starch microsphere hemostatic powder.

[0022] Example 4 (1) Preparation of porous starch The starch was dissolved in distilled water at a ratio of 1:9 (m / m), and ultrasonically treated with a homogenizer at 20 kHz and 170 W for 30 min at 20 °C. The suspension was centrifuged, and the lower precipitate was taken out and transferred to a vacuum drying oven and dried at 60 °C for 10 h. (2) Preparation of sodium carboxymethyl starch The product obtained in step (1) was dissolved in distilled water at a ratio of 1:9 (m / m), and a 2% NaOH solution was added to adjust the pH to 10.2. After sufficient reaction at 60° C., chloroacetic acid was added with starch at a ratio of 1:10 (m / m), and stirring was continued for 7 hours. The obtained product was washed with a large amount of distilled water, and then dehydrated and washed with ethanol. After washing, the solid-liquid mixture was separated and transferred to a Buchner funnel for vacuum filtration, and washed with ethanol continuously to remove the reaction residue. After repeating for more than three times, the mixture was transferred to a vacuum drying oven and dried at 70° C. for 8 hours to obtain the product sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen were dissolved in distilled water at a ratio of 1:1:9 (m / m / m), and the resulting solution was poured into a PEG solution (40%, w / w) at a ratio of 1:5 (v / v), stirred at 300 rpm for 15 min at 50°C, allowed to stand at 4°C for 24 h, and the lower precipitate was removed after centrifugation, washed with ethanol, transferred to a vacuum drying oven, and dried at 60°C for 10 h; (4) Preparation of cross-linked sodium carboxymethyl starch The product obtained in step (3) was dissolved in distilled water at a ratio of 1:9 (m / m), and gelatinized at 30° C. for 60 min. After the solution was mixed evenly, 1.0 g of a cross-linking agent was added, and the mixture was stirred at 70° C. and 300 rpm for 3.0 h to obtain a cross-linked sodium carboxymethyl starch emulsion; (5) Preparation of porous starch microsphere hemostatic powder The emulsion obtained in step (4) was allowed to stand for stratification, and the lower layer of milky white liquid was taken. Ethanol was added at a ratio of 1:5 (v / v) and stirred. After stratification again, the lower layer of milky white solid-liquid mixture was transferred to a Buchner funnel for vacuum filtration. The filtered product was transferred to a vacuum drying oven and dried at 60°C for 10 h to obtain a white solid powder. The obtained product was porous starch microsphere hemostatic powder.

Claims

1. A method for preparing porous starch microsphere hemostatic powder, characterized in that: The steps and conditions are as follows: (1) Preparation of porous starch The starch is dissolved in water, homogenized, centrifuged, the lower precipitate is removed and dried, and porous starch is obtained; (2) Preparation of sodium carboxymethyl starch The porous starch obtained in step (1) is dissolved in water, and an alkali is added to adjust the pH value and then fully reacted, and chloroacetic acid is added to the starch to continue the reaction, and the product is washed and dried to obtain sodium carboxymethyl starch; (3) Preparation of collagen cross-linked starch microspheres The product obtained in step (2) and collagen are dissolved in distilled water at a ratio of 0.7-1.3:1.3-0.7:8 (m / m / m), poured into a PEG solution, stirred, centrifuged, and the lower precipitate is removed and dried to obtain collagen cross-linked starch microspheres; (4) Preparation of cross-linked sodium carboxymethyl starch The collagen cross-linked starch microspheres obtained in step (3) are placed in water, gelatinized and mixed evenly with the solution, and then 0.1-1.0 g of a cross-linking agent is added, and the mixture is stirred at 60-80° C. to obtain a cross-linked sodium carboxymethyl starch emulsion; (5) Preparation of porous starch microsphere hemostatic powder The cross-linked sodium carboxymethyl starch emulsion obtained in step (4) is allowed to stand for stratification, the lower layer of liquid is taken, ethanol is added and stirred, and the mixture is allowed to stand for stratification, the lower layer of solid-liquid mixture is filtered under reduced pressure, and the obtained solid is dried to obtain porous starch microsphere hemostatic powder.

2. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The starch in (1) is common corn starch, potato starch, sweet potato starch, etc.

3. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The alkali in (2) is one or more of sodium hydroxide, calcium hydroxide and potassium hydroxide.

4. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The pH value in (2) should be greater than 8.

5. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The amount of chloroacetic acid added in the above-mentioned (2) is starch: chloroacetic acid = 0.8-1.2: 7-10 (m / m).

6. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The cross-linking agent in (4) can be sodium trimetaphosphate, sodium hexametaphosphate, etc.

7. The method for preparing porous starch microsphere hemostatic powder according to claim 1, characterized in that: The PEG in (5) includes PEG 300 and PEG 400.

8. Porous starch microsphere hemostatic powder prepared according to the method according to any one of claims 1 to 7.

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