阅读说明：本技术 一种水溶性止血海绵及其制备方法 (Water-soluble hemostatic sponge and preparation method thereof ) 是由 王纯斌 王纯保 肖亚兰 于 2021-09-28 设计创作，主要内容包括：本发明公开了一种水溶性止血海绵及其制备方法,包括如下步骤：1)按照比例准备原料：明胶(9.5-10.5)g、蒸馏水(88-92)mL、0.25％戊二醛溶液(2.8-3.2)mL、0.5％甲醛(2.4-2.6)mL；2)将明胶倒入蒸馏水中,浸泡10分钟,水浴加热,搅拌溶解,加入0.5％甲醛,高速搅拌均匀,起泡得到混合液体泡沫；3)将液体泡沫注入不同规格的模具中,-40至-80℃预冷冻后进行冷冻干燥得到海绵；4)将海绵采用0.25％戊二醛溶液交联,交联完成后使用蒸馏水洗涤数次后再次冷冻干燥成型,得到水溶性止血海绵。在36.2℃水中,1克所述的水溶性止血海绵6小时内完全溶解。(The invention discloses a water-soluble hemostatic sponge and a preparation method thereof, and the preparation method comprises the following steps: 1) preparing raw materials according to the proportion: gelatin (9.5-10.5) g, distilled water (88-92) mL, 0.25% glutaraldehyde solution (2.8-3.2) mL, 0.5% formaldehyde (2.4-2.6) mL; 2) pouring gelatin into distilled water, soaking for 10 minutes, heating in water bath, stirring for dissolving, adding 0.5% formaldehyde, stirring uniformly at high speed, and foaming to obtain mixed liquid foam; 3) injecting the liquid foam into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then carrying out freeze drying to obtain a sponge; 4) and (3) crosslinking the sponge by adopting 0.25% glutaraldehyde solution, washing the crosslinked sponge for a plurality of times by using distilled water after crosslinking is finished, and then carrying out freeze drying and forming again to obtain the water-soluble hemostatic sponge. In water at 36.2 ℃, 1 g of the water-soluble hemostatic sponge is completely dissolved within 6 hours.)

1. A preparation method of water-soluble hemostatic sponge is characterized by comprising the following steps: the method comprises the following steps:

1) preparing raw materials according to the proportion: gelatin (9.5-10.5) g, distilled water (88-92) mL, 0.25% v/v glutaraldehyde solution (2.8-3.2) mL, 0.5% (v/v) formaldehyde (2.4-2.6) mL;

2) pouring gelatin into distilled water, soaking for 10 minutes, heating in water bath, stirring for dissolving, adding 0.5% v/v formaldehyde, and stirring at high speed;

3) injecting the mixed liquid foam obtained in the previous step into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then carrying out freeze drying to obtain sponge;

4) and (3) crosslinking the sponge obtained in the previous step by adopting 0.25% v/v glutaraldehyde solution, washing the crosslinked sponge for a plurality of times by using distilled water after crosslinking is finished, then carrying out freeze drying and forming again, sealing, and then sterilizing by adopting cobalt-60 to obtain the water-soluble hemostatic sponge.

2. The method for preparing a water-soluble hemostatic sponge according to claim 1, wherein the method comprises the following steps: the raw materials prepared according to the proportion in step 1) are gelatin 10g, distilled water 90g, 0.25% v/v glutaraldehyde solution 3ml, 0.5% formaldehyde 2.5 ml.

3. The method for preparing a water-soluble hemostatic sponge according to claim 1, wherein the method comprises the following steps: heating in water bath at 60-70 deg.C in step 2).

4. The method for preparing a water-soluble hemostatic sponge according to claim 1, wherein the method comprises the following steps: the high-speed stirring in the step 2) is 200-400rpm stirring for 20-30 min.

5. The method for preparing a water-soluble hemostatic sponge according to claim 1, wherein the method comprises the following steps: washing for a plurality of times in the step 4), namely washing for 2-4 times.

6. A water-soluble hemostatic sponge, comprising: the method for preparing a water-soluble hemostatic sponge according to any one of claims 1-5, wherein 1 gram of said water-soluble hemostatic sponge is completely dissolved in water at 36.2 ℃ within 6 hours.

[ technical field ] A method for producing a semiconductor device

The invention relates to the technical field of polymer medical materials, in particular to a water-soluble hemostatic sponge and a preparation method thereof.

[ background of the invention ]

Blood is an important carrier for conveying oxygen to an organism, and when a human body loses too much blood due to injury, organs and cells can generate functional disorder and failure, so that life safety is influenced. Uncontrolled bleeding has always been the primary cause of casualties in war or major accidents. In modern war, 75% of casualty events in battlefield are caused by explosive fragments and gunshot injuries, and bleeding is still the main cause of death of battlefield wounds, so effective hemostasis can greatly reduce the death rate of the wounds. Due to the protection effect of personal protection devices such as body armor, helmets and the like, battlefield wounds often occur in limbs and limb connection parts such as armpits, groins, necks and the like, and bleeding can not be stopped by tourniquets or manual compression at the parts, so hemorrhagic shock and even death are easily caused. Therefore, the effective and rapid hemostasis is the key to improving the survival rate of the wounded in the battlefield or in the major accident.

The hemostatic sponge is used for rapidly stopping bleeding, inhibiting bacteria and resisting infection, absorbing a large amount of blood and tissue seepage and accelerating wound healing. The normal hemostasis of the body mainly depends on the structure and function of the intact blood vessel wall, the effective quality and quantity of blood platelets and the activity of normal blood coagulation factors, wherein the effects of the blood platelets with negative charges and the blood coagulation factors are the main. The hemostatic sponge is a hemostatic material which is fine, porous and positively charged, and can immediately adhere and aggregate platelets when contacting human blood, so that the blood forms thrombus and blocks wounds, various factors related to blood coagulation are released, and the blood forms stable fibrin polymers under the combined action of endogenous and exogenous blood coagulation paths, so that blood clots are formed, and the purpose of wound hemostasis is achieved.

Currently, there are studies on hemostatic sponges, for example, chinese patent application No. CN202110319395.1 discloses a degradable hemostatic sponge and a preparation method and application thereof, and a degradable drug-loaded hemostatic sponge, which is prepared by freeze-drying raw materials including cross-linked modified starch and cellulose; the mass ratio of the cross-linked modified starch to the cellulose is (0.2-5):1, and the degradable hemostatic sponge provided has the advantages of high water absorption rate, large water absorption capacity, high support strength after water absorption and long support time; the material is a plant source material and can be completely biodegraded; the degradable medicine carrying starch hemostatic sponge that provides, sponge surface are attached to there is the medicine carrying coating, and the slow degradation through auxiliary material in the medicine coating realizes the slow release of medicine, can reach the medicine release time that is equivalent with sponge supporting time through adjusting the auxiliary material composition, puts into the effect position back in the hemostasis of degradable medicine carrying starch hemostatic sponge, slow release medicine when maintaining the support.

The fast hemostatic materials reported at present mainly comprise powders (zeolite, collagen powder and potato starch), porous sponges (gelatin sponge and collagen sponge), oxidized regenerated cellulose, fibrin glue and the like, and have certain defects: the tissue adhesion of gelatin and collagen is poor, and both of them depend on sufficient platelets and coagulation factors for their hemostatic function; fibrin is derived from blood and may cause viral infection; porous zeolite and potato starch give off a large amount of heat after absorbing moisture in blood, and easily cause inflammation of wounds. Particularly, the conventional hemostatic sponge made of gelatin is degraded in a human body after operation and needs protease to participate, and in many cases, the protease in the human body is not enough to decompose the hemostatic sponge left in the body, or the protease cannot reach the part where the hemostatic sponge is placed, particularly in superficial operations such as thyroid gland and the like, and the hemostatic sponge which is not completely decomposed after the operation is very easy to form cyst. Therefore, there is a need to develop a water-soluble hemostatic sponge.

[ summary of the invention ]

Aiming at the problems that the conventional common hemostatic sponge made of gelatin is degraded in a human body after an operation and needs protease to participate, but in many cases, the protease of the human body is not enough to decompose the hemostatic sponge remained in the human body, or the protease cannot reach the part where the hemostatic sponge is placed, and the common hemostatic sponge cannot be completely decomposed, the water-soluble hemostatic sponge and the preparation method thereof are provided, the obtained water-soluble hemostatic sponge is suitable for hemostasis of the body surface and the operation, the appearance, hemostasis, water absorption and the like are the same as those of the common hemostatic sponge, and the water-soluble hemostatic sponge can be slowly dissolved when being contacted with water or body fluid at 36.2 ℃.

The purpose of the invention is realized by the following technical scheme:

a preparation method of a water-soluble hemostatic sponge comprises the following steps:

1) preparing raw materials according to the proportion: gelatin (9.5-10.5) g, distilled water (88-92) mL, 0.25% (v/v) glutaraldehyde solution (2.8-3.2) mL, 0.5% (v/v) formaldehyde (2.4-2.6) mL;

2) pouring gelatin into distilled water, soaking for 10 minutes, heating in water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and stirring at high speed to obtain a liquid foam mixed solution;

3) injecting the mixed solution obtained in the previous step into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain sponge;

4) and (3) crosslinking the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked sponge for a plurality of times by using distilled water after the crosslinking is finished, then carrying out freeze drying and forming again, sealing, and sterilizing by adopting cobalt-60 to obtain the water-soluble hemostatic sponge.

In the invention:

the raw materials prepared according to the proportion in the step 1) are 10g of gelatin, 90g of distilled water, 3ml of 0.25% glutaraldehyde solution and 2.5ml of 0.5% formaldehyde.

Heating in water bath at 60-70 deg.C in step 2).

The high-speed stirring in the step 2) is 200-400rpm stirring for 20-30 min.

Washing for a plurality of times in the step 4), namely washing for 2-4 times.

The invention also relates to the water-soluble hemostatic sponge obtained by the preparation method of the water-soluble hemostatic sponge, which has the same appearance, hemostasis and water absorption as the common hemostatic sponge, and has the outstanding advantages that the water-soluble hemostatic sponge can be slowly dissolved when being contacted with water or body fluid at 36.2 ℃, and can be completely dissolved within 6 hours in 1 g of water-soluble hemostatic sponge in water at 36.2 ℃, so that the aim of surgical hemostasis is fulfilled, and cysts cannot be formed in vivo.

Compared with the prior art, the invention has the following advantages:

gelatin is a high-protein product, the conventional hemostatic sponge made of gelatin is degraded in a human body after an operation and needs protease to participate, and in many cases, the protease in the human body is not enough to decompose the hemostatic sponge remained in the body, or the protease cannot reach the part where the hemostatic sponge is placed, especially the superficial operations such as thyroid gland and the like, and the hemostatic sponge which is not completely decomposed after the operation is very easy to form cyst. The appearance and hemostasis, water absorption and the like of the water-soluble hemostatic sponge are the same as those of the common hemostatic sponge, but the water-soluble hemostatic sponge can be slowly dissolved when being contacted with water or body fluid at 36.2 ℃, and can be completely dissolved in 1 g of the water-soluble hemostatic sponge within 6 hours in the water at 36.2 ℃, so that the aim of surgical hemostasis is fulfilled, and cysts cannot be formed in a body.

[ detailed description ] embodiments

The following examples are provided to further illustrate the embodiments of the present invention.

Example 1:

a preparation method of a water-soluble hemostatic sponge comprises the following steps:

1) preparing raw materials according to the proportion: 10g of gelatin, 90g of distilled water, 3ml of 0.25% glutaraldehyde solution and 2.5ml of 0.5% formaldehyde;

2) pouring gelatin into distilled water, soaking for 10 minutes, heating in 65 ℃ water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and uniformly stirring at high speed (400rpm for 20min) to obtain a foam liquid mixed solution;

3) injecting the mixed solution obtained in the previous step into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain sponge;

4) and (3) crosslinking the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked sponge for 3 times by using distilled water after crosslinking is finished, then carrying out freeze drying and forming again, sealing, and then sterilizing by adopting cobalt-60 to obtain the water-soluble hemostatic sponge.

Example 2:

a preparation method of a water-soluble hemostatic sponge comprises the following steps:

1) preparing raw materials according to the proportion: 9.5g of gelatin, 92mL of distilled water, 2.8mL of 0.25% (v/v) glutaraldehyde solution, and 2.6mL of 0.5% (v/v) formaldehyde;

2) pouring gelatin into distilled water, soaking for 10 minutes, heating in water bath at 60 ℃, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and uniformly stirring at high speed (300rpm for 25min) to obtain a foam liquid mixed solution;

3) injecting the mixed solution obtained in the previous step into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain sponge;

4) and (3) crosslinking the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked sponge for 2 times by using distilled water after the crosslinking is finished, then carrying out freeze drying and forming again, sealing, and sterilizing by adopting cobalt-60 to obtain the water-soluble hemostatic sponge.

Example 3:

a preparation method of a water-soluble hemostatic sponge comprises the following steps:

1) preparing raw materials according to the proportion: 10.5g of gelatin, 88mL of distilled water, 3.2mL of 0.25% (v/v) glutaraldehyde solution, and 2.4mL of 0.5% (v/v) formaldehyde;

2) pouring gelatin into distilled water, soaking for 10 minutes, heating in 70 ℃ water bath, stirring for dissolving, adding 0.5% (v/v) formaldehyde, and uniformly stirring at a high speed (200rpm for 30min) to obtain a foam liquid mixed solution;

3) injecting the mixed solution obtained in the previous step into moulds with different specifications, pre-freezing at-40 to-80 ℃, and then performing freeze drying to obtain sponge;

4) and (3) crosslinking the sponge obtained in the previous step by adopting 0.25% (v/v) glutaraldehyde solution, washing the crosslinked sponge for 4 times by using distilled water after crosslinking is finished, then carrying out freeze drying and forming again, sealing, and then sterilizing by adopting cobalt-60 to obtain the water-soluble hemostatic sponge.

Comparative example:

according to CN202110319395.1, the preparation method of the degradable hemostatic sponge comprises the following steps:

1) weighing 100.0g of potato starch in a reaction kettle, adding 4900ml of water into the reaction kettle, setting the temperature of a jacket reaction kettle to be 80 ℃, and stirring at a constant temperature of 200rpm for 1 h; reducing the temperature of a jacket reaction kettle to 50 ℃, adjusting the pH of a reaction solution to 9 by using a NaOH solution with the concentration of 1mol/L, dropwise adding 10ml of an epoxy chloropropane aqueous solution into the reaction solution by using a constant-pressure titration funnel, reacting at a high temperature for 4 hours, pouring out the reaction solution after the reaction is finished, cooling, separating out a product by using 12.5L of absolute ethyl alcohol, washing the product for 2-3 times by using 2L of absolute ethyl alcohol, and drying for 24 hours at 50 ℃ to obtain the cross-linked modified potato starch;

2) weighing 1.0g of carboxymethyl cellulose in 39ml of water, stirring at 400rpm in a water bath at 40 ℃ for 4 hours to completely dissolve the carboxymethyl cellulose into uniform transparent gel, adjusting the pH value of the carboxymethyl cellulose solution to 3 by using 1mol/L HCl, and cooling to room temperature for later use;

3) weighing 2.0g of cross-linked modified potato starch in 58ml of water, stirring and dissolving at normal temperature for 20min to ensure that the cross-linked starch absorbs water and is saturated, pouring the cross-linked modified potato starch into a carboxymethyl cellulose solution, stirring at 400rpm for 30min to uniformly mix, adjusting the pH of the solution to 6 by using 1mol/L HCl after uniform mixing, and standing for more than 12h to remove bubbles in the solution;

4) pouring the mixed solution into a precooling mold, standing for 30min, covering a mold cover, placing the mold cover in a freezing refrigerator at the temperature of minus 40 ℃ for prefreezing for 4h, removing the mold cover after prefreezing is finished, and placing the mold carrying the sample in a freezing drying box for freezing and drying for 72h at the temperature of minus 60 ℃ and minus 0.1MPa to obtain the degradable starch hemostatic sponge.

Experimental example 1:

the hemostatic sponges obtained in the examples and comparative examples were placed in water and observed for dissolution:

	whether the hemostatic sponge can be completely dissolved in water of 36.2 ℃ within 6 hours or not by 1 g
		Example 1	Is that
Example 2	Is that
		Example 3	Is that
Comparative example	Whether or not

As can be seen from the above table, the water-soluble hemostatic sponges obtained in the examples were completely dissolved in water at 36.2 ℃ for 6 hours in 1 g of the water-soluble hemostatic sponge, while the hemostatic sponges obtained in the comparative example were not completely dissolved in water at 6 hours.

Experimental example 2:

based on example 1, the effect of different amounts of 0.25% (v/v) glutaraldehyde solution added on the dissolution of the resulting hemostatic sponge in water was investigated:

as can be seen from the above table, the adding amount of 0.25% (v/v) glutaraldehyde solution has an influence on the dissolution of the obtained hemostatic sponge in water, the adding amount of 0.25% (v/v) glutaraldehyde solution is in the range of (2.8-3.2) mL, 1 gram of the obtained hemostatic sponge can be completely dissolved in 6 hours in water at 36.2 ℃, the other adding amounts of the obtained hemostatic sponge cannot be completely dissolved, and the analysis reason is that too much 0.25% (v/v) glutaraldehyde solution is added, so that different tissue components in the hemostatic sponge are connected too tightly, and the solubility of the hemostatic sponge in water is influenced; the addition of too little 0.25% (v/v) glutaraldehyde solution results in loose connection of the different tissue components in the blood sponge, which affects the hemostatic effect of the hemostatic sponge, so that the addition of 0.25% (v/v) glutaraldehyde solution in the range of (2.8-3.2) mL is suitable.

The above description is intended to describe in detail the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the claims of the present invention, and all equivalent changes and modifications made within the technical spirit of the present invention should fall within the scope of the claims of the present invention.