Starch-Based Fluffy Particle, Preparation Method and Use Thereof

Abstract

The present disclosure discloses a starch-based fluffy particle, a preparation method and use thereof. The preparation method of the starch-based fluffy particle comprises the following steps of: (1) adding water into starch or modified starch for gelatinization to obtain a starch paste; (2) adding the starch paste into a polar organic solvent, stirring, standing and centrifuging to collecting a precipitate; and (3) freeze-drying, crushing and sieving the precipitate in sequence to prepare the starch-based fluffy particle. The starch-based fluffy particles are porous and fluffy with a large pore size, have excellent water absorption speed, water absorption rate and degradation rate, and can achieve the purpose of rapid and efficient hemostasis. Moreover, the starch-based fluffy particles are free of dispersing agent, emulsifying agent or cross-linking agent, have the characteristics of safety and reliability, and can meet the hemostatic requirement of in-vivo environment.

Claims

1. A preparation method of a starch-based fluffy particle, comprising: (1) adding water into starch or modified starch for gelatinization to obtain a starch paste; (2) adding the starch paste into a polar organic solvent that does not dissolve the starch paste so that the starch paste is dispersed into several precipitates in the polar organic solvent and the precipitates are swelled, stirring, standing and centrifuging to collect precipitates; and (3) freeze-drying, crushing and sieving the precipitates in sequence to prepare the starch-based fluffy particle.

2. The preparation method according to claim 1, wherein in step (1), the modified starch is at least one selected from the group consisting of etherified starch, carboxymethylated starch, esterified starch, and crosslinked starch.

3. The preparation method according to claim 1, wherein in step (1), a mass ratio of the starch or the modified starch to the water in the starch paste is in the range of 1:3 to 1:40.

4. The preparation method according to claim 1, wherein in step (2), the polar organic solvent is at least one selected from the group consisting of methanol, ethanol, propanol, butanol, acetone, isopropanol, and dimethyl sulfoxide.

5. The preparation method according to claim 4, wherein in step (2), the organic solvent is at least one of the follwoing: isopropanol, methanol, ethanol, a combination of isopropanol and methano, and dimethyl sulfoxide or acetone.

6. The preparation method according to claim 1, wherein the starch-based fluffy particle further comprises a hydrophilic polymer material.

7. The preparation method according to claim 1, wherein in step (2), the stirring is performed at a rotating speed of 100 r/min to 3,000 r/min, and lasts for 0.5 hour to 2 hours.

8. The preparation method according to claim 1, wherein in step (2), the centrifuging is performed at a rotating speed of 2,000 r/min to 5,000 r/min.

9. The preparation method according to claim 1, wherein in step (3), the freeze-drying comprises the steps of: freezing the precipitates at −30° C. to −10° C. for 3 hours to 24 hours first, and then freeze-drying the precipitates in a freeze dryer at −50° C. to −30° C. for 15 hours to 36 hours.

10. A starch-based fluffy particle prepared by the preparation method according to claim 1, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

11. (canceled)

12. A medical hemostatic material, comprising the starch-based fluffy particle according to claim 10.

13. A starch-based fluffy particle prepared by the preparation method according to claim 2, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

14. A starch-based fluffy particle prepared by the preparation method according to claim 3, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

15. A starch-based fluffy particle prepared by the preparation method according to claim 4, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

16. A starch-based fluffy particle prepared by the preparation method according to claim 5, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

17. A starch-based fluffy particle prepared by the preparation method according to claim 6, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

18. A starch-based fluffy particle prepared by the preparation method according to claim 7, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

19. A starch-based fluffy particle prepared by the preparation method according to claim 8, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

20. A starch-based fluffy particle prepared by the preparation method according to claim 9, wherein a particle size of the starch-based fluffy particle is from 20 μm to 500 μm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0029] FIG. 1 shows the micro-structure of dried carboxymethyl corn starch-based precipitates in Example 1 and the micro-structure of dried carboxymethyl corn starch-based precipitates in Example 1 after crushing, wherein A represents the micro-structure of the dried carboxymethyl corn starch-based precipitates in Example 1, and B represents the micro-structure of the dried carboxymethyl corn starch-based precipitates in Example 1 after crushing.

[0030] FIG. 2 shows the results of the carboxymethyl corn starch-based fluffy particles in Example 1 and the carboxymethyl corn starch raw powder after 20 times of water adsorption, wherein A represents the carboxymethyl corn starch-based fluffy particles, and B represents the carboxymethyl corn starch raw powder.

[0031] FIG. 3 shows the gel stability results of different types of starch particles after 20 times of water adsorption, wherein C represents a German hemostatic powder (hemostatic powder prepared from potato starch by a cross-linking technology), D represents the carboxymethyl potato starch without any treatment, E represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, and F represents the carboxymethyl corn starch-based fluffy particles prepared in Example 1.

[0032] FIG. 4 shows the gel stability results of different types of starch particles after water adsorption and standing for 48 hours, wherein G represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, H represents the carboxymethyl corn starch-based fluffy particles prepared in Example 1, and I represents the German product (the hemostatic powder prepared from potato starch by a cross-linking technology).

[0033] FIG. 5 shows the gel stability results of the carboxymethyl potato starch-based fluffy particles prepared in Example 2 and a Chinese market product after 20 times of water adsorption, wherein J represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, and K represents the Chinese market product (a product prepared according to the Chinese patent CN200610053680.9).

DETAILED DESCRIPTION

[0034] In order to make those skilled in the art better understand the technical solutions of the present disclosure, the following examples are now provided for description. It should be pointed out that the following examples do not limit the scope of protection claimed in the present disclosure.

[0035] Unless otherwise specified, the raw materials, reagents or devices used in the following examples may all be obtained in conventional commercial ways, or obtained by existing known methods.

Example 1

[0036] The example provided a carboxymethyl corn starch-based fluffy particle, and a preparation method of the carboxymethyl corn starch-based fluffy particle comprised the following steps.

[0037] (1) 1 g of carboxymethyl corn starch with a degree of substitution of 0.24 was added into 10 mL of distilled water, and stirred evenly at room temperature to prepare a carboxymethyl corn starch paste.

[0038] (2) An aqueous solution containing 95% methanol was prepared, and the carboxymethyl corn starch paste was transferred into 20 mL of methanol solution at a stirring speed of 1,000 r/min and room temperature, continuously stirred for 0.5 hour after finishing transferring, and then stood for 3 hours. The supernatant liquid was dumped, the lower layer containing the solvent and the starch-based precipitate was centrifuged at a rotating speed of 3,000 r/min to remove most of the solvent adsorbed on the starch-based precipitate, and the starch-based precipitate was collected.

[0039] (3) The collected starch-based precipitate was frozen in a refrigerator at −20° C. for 15 hours, and then freeze-dried in a freeze dryer at −50° C. for 20 hours to obtain dried carboxymethyl corn starch-based precipitate.

[0040] (4) The dried carboxymethyl corn starch-based precipitate was crushed, and then sieved with an 80-mesh sieve to obtain crushed precipitates with a particle size less than 200 μm. Then, the obtained crushed precipitates were sieved with a 300-mesh sieve to remove the crushed precipitates with a particle size less than 50 μm, so as to obtain carboxymethyl corn starch-based fluffy particles with a particle size of 50 μm to 200 μm.

[0041] In FIG. 1, A represents the micro-structure of the dried carboxymethyl corn starch-based precipitates obtained in this example, and in FIG. 1, B represents the micro-structure of the dried carboxymethyl corn starch-based precipitates obtained in this example after crushing. It can be seen from FIG. 1 that the starch particles inside the dried carboxymethyl corn starch-based precipitates are entangled and connected with each other, with a porous interior, and there are large gaps between the dried carboxymethyl corn starch-based precipitates, so that it is not easy to cause a capillary phenomenon.

[0042] in FIG. 2, A represents the result of the carboxymethyl corn starch-based fluffy particles prepared this example after 20 times of water adsorption, and in FIG. 2, B represents the result of the carboxymethyl corn starch raw powder after 20 times of water adsorption. It can be seen from FIG. 2 that the carboxymethyl corn starch raw powder is in a flowing state, while the carboxymethyl corn starch-based fluffy particles prepared in this example can still be kept in a certain form, which indicates that an upper limit of water adsorption is still not reached. Another experiment shows that, compared with the carboxymethyl corn starch raw powder, the water absorption rate of the carboxymethyl corn starch-based fluffy particles prepared in this example is increased by more than 4 times on average, and the water absorption speed is accelerated, which can be reduced from 35 seconds to 10 seconds on average.

Example 2

[0043] The example provided a carboxymethyl potato starch-based fluffy particle, and a preparation method of the carboxymethyl potato starch-based fluffy particle comprised the following steps.

[0044] (1) 1 g of carboxymethyl potato starch with a degree of substitution of 0.3 was added into 10 mL of distilled water, and stirred evenly at room temperature to prepare a carboxymethyl potato starch paste.

[0045] (2) An aqueous solution containing 90% ethanol was prepared, and the carboxymethyl potato starch paste was transferred into 20 mL of ethanol solution at a stirring speed of 600 r/min and room temperature, continuously stirred for 0.5 hour after finishing transferring, and then stood for 3 hours. The supernatant liquid was dumped, the lower layer containing the solvent and the starch-based precipitate was centrifuged at a rotating speed of 2,000 r/min to remove most of the solvent adsorbed on the starch-based precipitate, and the starch-based precipitate was collected.

[0046] (3) The collected starch-based precipitate was frozen in a refrigerator at −28° C. for 20 hours, and then freeze-dried in a freeze dryer at −50° C. for 24 hours to obtain dried carboxymethyl potato starch-based precipitate.

[0047] (4) The dried carboxymethyl potato starch-based precipitate was crushed, and then sieved with an 80-mesh sieve to obtain crushed precipitates with a particle size less than 200 μm. Then, the obtained crushed precipitates were sieved with a 350-mesh sieve to remove the crushed precipitates with a particle size less than 30 μm, so as to obtain carboxymethyl potato starch-based fluffy particles with a particle size of 30 μm to 200 μm.

[0048] When the carboxymethyl potato starch-based fluffy particles prepared in this example were used in a hemostasis experiment of a broken tail of a mouse. The bleeding volume of the mouse during hemostasis was low, and the hemostasis time was short. Complete hemostasis could be realized within 100 seconds on average, and the hemostasis speed was much faster than that of Chinese and foreign hemostatic powder products that have a hemostasis time of more than 210 seconds.

Example 3

[0049] The example provided a polyoxyethylene/carboxymethyl potato starch-based fluffy particle, and a preparation method of the polyoxyethylene/carboxymethyl potato starch-based fluffy particle comprised the following steps.

[0050] (1) 0.1 g of polyoxyethylene powder with a molecular weight of 50,000 was dispersed in 20 mL of distilled water, and then 1 g of carboxymethyl potato starch with a degree of substitution of 0.3 was added, and stirred evenly at room temperature to prepare a polyoxyethylene/carboxymethyl potato starch paste.

[0051] (2) 50 mL of aqueous solution containing 95% isopropanol was prepared, and the polyoxyethylene/carboxymethyl potato starch paste was transferred into the 50 mL isopropanol solution at a stirring speed of 1,500 r/min and room temperature, continuously stirred for 0.5 hour after finishing transferring, and then stood for 3 hours. The supernatant liquid was dumped, the lower layer containing the solvent and the starch-based precipitate was centrifuged at a rotating speed of 3,000 r/min to remove most of the solvent adsorbed on the starch-based precipitate, and the starch-based precipitate was collected.

[0052] (3) The collected starch-based precipitate was frozen in a refrigerator at −30° C. for 10 hours, and then freeze-dried in a freeze dryer at −50° C. for 24 hours to obtain dried polyoxyethylene/carboxymethyl potato starch-based precipitate.

[0053] (4) The dried polyoxyethylene/carboxymethyl potato starch-based precipitate was crushed, and then sieved with an 80-mesh sieve to obtain crushed precipitates with a particle size less than 200 μm. Then, the obtained crushed precipitates were sieved with a 300-mesh sieve to remove the crushed precipitates with a particle size less than 50 μm, so as to obtain polyoxyethylene/carboxymethyl potato starch-based fluffy particles with a particle size of 50 μm to 200 μm.

[0054] In this example, the flexibility of carboxymethyl potato starch gel was further improved by adding polyoxyethylene into the carboxymethyl potato starch.

Example 4

[0055] The example provided a carboxymethyl potato starch-based fluffy particle, and a preparation method of the carboxymethyl potato starch-based fluffy particle comprised the following steps.

[0056] (1) 1 g of carboxymethyl potato starch with a degree of substitution of 0.3 was added into 10 mL of distilled water, and stirred evenly at room temperature to prepare a carboxymethyl potato starch paste.

[0057] (2) An aqueous solution containing 50% isopropanol and 45% methanol (i.e., an isopropanol-methanol aqueous solution) was prepared, and the carboxymethyl potato starch paste was transferred into 20 mL of isopropanol-methanol solution at a stirring speed of 600 r/min and room temperature, continuously stirred for 0.5 hour after finishing transferring, and then stood for 3 hours. The supernatant liquid was dumped, the lower layer containing the solvent and the starch-based precipitate was centrifuged at a rotating speed of 2,000 r/min to remove most of the solvent adsorbed on the starch-based precipitate, and the starch-based precipitate was collected.

[0058] (3) The collected starch-based precipitate was frozen in a refrigerator at −28° C. for 20 hours, and then freeze-dried in a freeze dryer at −50° C. for 24 hours to obtain dried carboxymethyl potato starch-based precipitate.

[0059] (4) The dried carboxymethyl potato starch-based precipitate was crushed, and then sieved with an 80-mesh sieve to obtain crushed precipitates with a particle size less than 200 μm. Then, the obtained crushed precipitates were sieved with a 350-mesh sieve to remove the crushed precipitates with a particle size less than 30 μm, so as to obtain carboxymethyl potato starch-based fluffy particles with a particle size of 30 μm to 200 μm.

[0060] Product Effect Test

[0061] FIG. 3 shows the gel stability results of different types of starch particles after 20 times of water adsorption, wherein C represents a German hemostatic powder (hemostatic powder prepared from potato starch by a cross-linking technology), D represents the carboxymethyl potato starch without any treatment, E represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, and F represents the carboxymethyl corn starch-based fluffy particles prepared in Example 1. It can be seen from FIG. 3 that the carboxymethyl potato starch without any treatment is in a flowing state, with a poor water absorption capacity, and the performance of the carboxymethyl potato starch without any treatment is far inferior to those of the German hemostatic powder and the starch-based fluffy particles prepared in Examples 1 to 2.

[0062] FIG. 4 shows the gel stability results of different types of starch particles after water adsorption and standing for 48 hours, wherein G represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, H represents the carboxymethyl corn starch-based fluffy particles prepared in Example 1, and I represents the German product (the hemostatic powder prepared from potato starch by the cross-linking technology). It can be seen from FIG. 4 that the German product is melt to flow, which indicates that the gel stability of the German product is not as good as those of the starch-based fluffy particles prepared in Examples 1 to 2.

[0063] FIG. 5 shows the gel stability results of the carboxymethyl potato starch-based fluffy particles prepared in Example 2 and a Chinese market product after 20 times of water adsorption, wherein J represents the carboxymethyl potato starch-based fluffy particles prepared in Example 2, and K represents the Chinese market product (a product prepared according to the Chinese patent CN200610053680.9). It can be seen from FIG. 5 that the carboxymethyl potato starch-based fluffy particles prepared in Example 2 are gel-like after water absorption, while the Chinese market product is dilute suspension, which indicates that the starch-based fluffy particles of the present disclosure have a better gel stability.

[0064] Tests, including water absorption, gel strength and adhesion work were performed on the starch-based fluffy particles prepared in Examples 1 to 4, the carboxymethyl corn starch, the carboxymethyl potato starch and three comparative products (which were namely comparative products 1 to 3). Test results are shown in Table 1. The comparative product 1 is hemostatic powder prepared from potato starch by a cross-linking technology; the comparative product 2 is a product prepared according to the Chinese patent CN200610045441.9; and the comparative product 3 is a product prepared according to the Chinese patent CN200610053680.9.

Water absorption rate=water absorption capacity (g or mL)/powder weight (g);

[0065] water absorption speed: time required for adsorbing 10 g of water with 0.5 g of powder (second);

[0066] gel strength: gel strength measured after the product is saturated with water and sealed standing for 48 hours; and

[0067] adhesion work (g.Math.mm): adhesion work of gel after saturated with water.

TABLE-US-00001 TABLE 1 Property test results of different types of starch particles Example Example Example Example Carboxymethyl Carboxymethyl Comparative Comparative Comparative Sample 1 2 3 4 corn starch potato starch product 1 product 2 product 3 Water 2000% 2500% 2200% 2800% 490% 900% 2400% 150% 250% absorption rate Water 22 19 24 18 120 60 20 300 120 absorption speed Gel strength 6.9 7.5 9 7.3 2.2 3.1 Reliquefaction 5.8 Reliquefaction (48 h, kPa) Adhesion work 72 78 90 74 22 28 70 120  20 (saturated absorption)

[0068] It can be seen from Table 1 that, compared with the carboxymethyl corn starch without any treatment and the carboxymethyl potato starch without any treatment, the starch-based fluffy particles prepared in Examples 1 to 4 of the present disclosure all have significantly better effects in water absorption, gel strength and adhesion work. Although the property of the German product is superior to those of the Chinese products 1 and 2, the property of the German product is inferior to those of the starch-based fluffy particles prepared in Examples 1 to 4, which indicates that the product prepared by the present disclosure has a better hemostatic property than conventional Chinese and foreign market products, and can be widely used in vivo and in vitro as a medical hemostatic material to achieve the purpose of fast and efficient hemostasis.