CN114377189B - Hemostatic composite hydrogel and preparation method and application thereof - Google Patents
Hemostatic composite hydrogel and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a hemostatic composite hydrogel and a preparation method and application thereof. The hemostatic composite hydrogel has strong mechanical property and good biological safety. The preparation raw materials have wide sources, the preparation process is simple, the preparation process is controllable, and the scale-up production can be realized.
Description
Technical Field
The invention belongs to the field of hydrogel, and particularly relates to a hemostatic composite hydrogel as well as a preparation method and application thereof.
Background
Thrombin is a clinical hemostatic drug and is mainly used for hemostasis of trauma, surgery and the like. The thrombin acts on the last step of the blood coagulation process to promote the conversion of soluble fibrinogen in the plasma into insoluble fibrin, thereby achieving the purpose of quick-acting hemostasis. However, the aqueous solution of thrombin is unstable at room temperature, which brings inconvenience to clinical application.
The existing hemostatic materials have the following problems: the hemostatic material is not stably wrapped in the base material due to poor adhesion between the hemostatic material and the bleeding wound surface, so that hemostasis fails, or the hemostatic material is not dispersed in the base material well and cannot be effectively released, so that the wound cannot be blocked in time, and hemostasis is not rapid enough.
Disclosure of Invention
The present invention has been made to solve at least one of the above-mentioned problems occurring in the prior art. Therefore, the invention provides a hemostatic composite hydrogel, wherein thrombin can be stably wrapped and rapidly released by the composite hydrogel, so that the effect of quick hemostasis is achieved.
The second aspect of the invention provides a preparation method of the hemostatic composite hydrogel.
In a third aspect, the invention provides a use of the hemostatic composite hydrogel in wound hemostasis.
According to a first aspect of the present invention, a hemostatic composite hydrogel is provided, wherein the hydrogel comprises a colloid formed by bovine serum albumin and surface-modified gelatin, and the colloid is wrapped by thrombin.
In some embodiments of the invention, the hemostatic composite hydrogel is made from components comprising: bovine serum albumin, surface-modified gelatin, and thrombin.
The hydrogel is a three-dimensional network material formed by crosslinking hydrophilic macromolecules, and has the characteristics of controllable physicochemical properties, good biocompatibility and the like.
Gelatin is a hydrolysate of collagen, has good biocompatibility and degradability and low immunogenicity, and retains cell adhesion peptide RGD (H-glycyl-arginyl-glycyl-aspartyl-asparaginyl-proline-OH) and protease degradation sites possessed by collagen.
In some embodiments of the invention, the mass ratio of the bovine serum albumin to the surface-modified gelatin is (2-5): 1.
In some preferred embodiments of the present invention, the mass ratio of the bovine serum albumin to the surface-modified gelatin is (3-5): 1.
In some embodiments of the invention, the concentration of thrombin in the hydrogel is between 0.2U/mL and 7U/mL.
In some preferred embodiments of the invention, the concentration of thrombin in the hydrogel is between 0.5U/mL and 5U/mL.
In some embodiments of the invention, the bovine serum albumin and the surface modified gelatin are crosslinked into a gel by physical action; the physical action includes at least one of hydrogen bonding and entanglement.
Thrombin used for hemostasis can be encapsulated in a physical network by forming the network through physical cross-linking.
In some embodiments of the invention, the modified gelatin is selected from at least one of methacrylic anhydride modified gelatin, acryloyl chloride modified gelatin, glyceryl methacrylate modified gelatin.
According to a second aspect of the present invention, there is provided a method for preparing a hemostatic composite hydrogel, comprising the steps of: and mixing the bovine serum albumin solution with the surface modified gelatin, heating, cooling, mixing with thrombin, and forming to obtain the hemostatic composite hydrogel.
In some embodiments of the invention, the heating temperature is 45 ℃ to 55 ℃.
In some preferred embodiments of the present invention, the heating temperature is 48 ℃ to 52 ℃.
In some embodiments of the invention, the temperature of the cooling is between 30 ℃ and 40 ℃.
In some preferred embodiments of the invention, the mixing is vortex mixing.
In some embodiments of the invention, the temperature of the forming is 20 ℃ to 30 ℃.
In some embodiments of the invention, the forming time is 10min to 20min.
In some preferred embodiments of the present invention, the molding time is 14min to 16min.
According to a third aspect of the present invention, there is provided a use of a hemostatic composite hydrogel in hemostasis of wounds.
The invention has the beneficial effects that:
1. the hemostatic composite hydrogel has strong mechanical property, does not introduce toxic micromolecules, and has good biological safety.
2. The hemostatic hydrogel prepared by the invention has simple preparation process, controllable preparation process and large-scale production.
3. The thrombin in the hemostatic composite hydrogel can be stably wrapped and quickly released, and the quick-acting hemostatic effect can be achieved when the hemostatic composite hydrogel is applied to wound hemostasis.
Drawings
The invention is further described with reference to the following figures and examples, in which:
FIG. 1 is a schematic diagram of the formation and release of thrombin in the hemostatic composite gel of the present invention.
FIG. 2 is a graph showing the hemostatic effect of the hydrogels of examples 1 to 5 of the present invention and comparative example 1, (a) blood is dropped onto the gel; and (b) adding double distilled water after 3 min.
FIG. 3 is a bar graph showing the results of the blood coagulation index test in examples 1 to 5 of the present invention and comparative example 1.
Detailed Description
The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.
Example 1
The embodiment prepares the hemostatic composite hydrogel, and the specific process comprises the following steps:
(1) Weighing 2.5g of bovine serum albumin, dissolving the bovine serum albumin in 10mL of aqueous solution to prepare 25% bovine serum albumin aqueous solution, uniformly stirring at room temperature, adding 0.625g of methacrylate esterified gelatin, heating to 50 ℃, and stirring to uniformly dissolve the bovine serum albumin aqueous solution;
(2) Cooled to 37 ℃ and 200. Mu.L of the cooled solution was added with 10. Mu.L of a 100U/mL thrombin solution.
(3) Vortex, mix well, cool for 15min at room temperature and shape.
Example 2
The embodiment prepares the hemostatic composite hydrogel, and the specific process comprises the following steps:
(1) Weighing 2.5g of bovine serum albumin, dissolving the bovine serum albumin in 10mL of aqueous solution to prepare 25% bovine serum albumin aqueous solution, uniformly stirring at room temperature, adding 0.625g of methacrylate-esterified gelatin, heating to 50 ℃, stirring, and uniformly dissolving;
(2) Cooled to 37 ℃ and 200. Mu.L of the cooled solution was added with 5. Mu.L of a 100U/mL thrombin solution.
(3) Vortex, mix well, cool for 15min at room temperature and shape.
Example 3
The embodiment prepares the hemostatic composite hydrogel, and the specific process comprises the following steps:
(1) Weighing 2.5g of bovine serum albumin, dissolving the bovine serum albumin in 10mL of aqueous solution to prepare 25% bovine serum albumin aqueous solution, uniformly stirring at room temperature, adding 0.625g of methacrylate-esterified gelatin, heating to 50 ℃, stirring, and uniformly dissolving;
(2) Cooled to 37 ℃ and 200. Mu.L of the cooled solution was added with 2. Mu.L of a 100U/mL thrombin solution.
(3) Vortex, mix well, cool for 15min at room temperature and shape.
Example 4
This example prepares a hemostatic composite hydrogel, and the specific process is as follows:
(1) Weighing 2.5g of bovine serum albumin, dissolving the bovine serum albumin in 10mL of aqueous solution to prepare 25% bovine serum albumin aqueous solution, uniformly stirring at room temperature, adding 0.625g of methacrylate-esterified gelatin, heating to 50 ℃, stirring, and uniformly dissolving;
(2) Cooled to 37 ℃ and 200. Mu.L of the cooled solution was added with 1. Mu.L of a 100U/mL thrombin solution.
(3) Vortex, mix well, cool for 15min at room temperature and shape.
Comparative example 1
The comparative example prepares a composite hydrogel, and the specific process is as follows:
(1) Weighing 2.5g of bovine serum albumin, dissolving the bovine serum albumin in 10mL of aqueous solution to prepare 25% bovine serum albumin aqueous solution, uniformly stirring at room temperature, adding 0.625g of methacrylate esterified gelatin, heating to 50 ℃, and stirring to uniformly dissolve the bovine serum albumin aqueous solution;
(2) Cooled to 37 ℃ and 200. Mu.L of the cooled solution was taken.
(3) Vortex, mix well, cool for 15min at room temperature and shape.
Test examples
Experiment raw materials: fresh Rabbit Whole blood, 0.2MCaCl 2 And (3) solution.
10mg of each of the samples of examples 1 to 5 and comparative example 1 was weighed and placed in a small dish. Add premixed 100. Mu.L whole blood and 10. Mu.L of LCaCl 2 And (3) solution. After 3min of standing, 5mL of double distilled water was added to each sample dish to destroy non-thrombosed erythrocytes. mu.L of each sample was added to a 96-well plate, and the absorbance of the sample at 545nm was measured. A blank control was prepared by adding 5mL of double distilled water to 100. Mu.L of whole blood. Each sample was tested 3 times and the average was taken.
The results of the experiment are shown in table 1 and fig. 2.
The formula for calculating the blood coagulation index is: blood coagulation index (%) = a s /A b X 100% where A s Is the absorbance value of the sample, A b Absorbance values for the blanks.
TABLE 1 hydrogel coagulation index test data for examples 1-5 and comparative example 1
And (4) analyzing results: as can be seen from Table 1 and FIG. 2, the hemostatic composite hydrogels prepared in examples 1 to 3 have significant blood coagulation effects, and the blood coagulation indexes are 15.6 + -0.0016, 14.9 + -0.0013 and 14.6 + -0.0041, respectively, and the hemostatic composite hydrogels prepared in example 4 with too small thrombin addition and comparative example 1 without thrombin addition have poor blood coagulation effects. The composite hydrogel can realize rapid release hemostasis after wrapping thrombin, and the coagulation effect is increased along with the increase of the concentration of the thrombin in a certain range.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the embodiments, and various changes can be made without departing from the gist of the present invention within the knowledge of those skilled in the art. Furthermore, the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.
Claims (4)
1. A hemostatic composite hydrogel is characterized by being prepared from the following components: bovine serum albumin, methacrylic anhydride modified gelatin, and thrombin; the hydrogel comprises a colloid formed by bovine serum albumin and methacrylic anhydride modified gelatin, and thrombin is wrapped by the colloid; crosslinking the bovine serum albumin and the methacrylic anhydride modified gelatin into gel through physical action; the physical effect comprises at least one of hydrogen bonding and entanglement; the concentration of the thrombin in the hydrogel is 0.5U/mL-5U/mL; the hydrogel is prepared by a method comprising the following steps: mixing bovine serum albumin solution with methacrylic anhydride modified gelatin, heating, cooling, mixing with thrombin, and molding to obtain the hemostatic composite hydrogel; the mass ratio of the bovine serum albumin to the methacrylic anhydride modified gelatin is (2-5) to 1.
2. The hemostatic composite hydrogel according to claim 1, wherein the heating temperature is 45 ℃ to 55 ℃.
3. The hemostatic composite hydrogel according to claim 1, wherein the forming temperature is 20 ℃ to 30 ℃.
4. Use of a haemostatic composite hydrogel according to any of claims 1-3 in the preparation of a wound haemostatic material.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009128474A1 (en) * | 2008-04-16 | 2009-10-22 | 財団法人化学及血清療法研究所 | Method of producing thrombin-immobilized bioabsorbable sheet preparation |
| KR20190062170A (en) * | 2017-11-28 | 2019-06-05 | (주)다림티센 | Hemostatic agent and container containing the same |
| CN112368028A (en) * | 2018-05-09 | 2021-02-12 | 弗罗桑医疗设备公司 | Method for preparing a hemostatic composition |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2881651A1 (en) * | 2005-02-09 | 2006-08-11 | Urodelia Sa | NEW PHARMACEUTICAL PRODUCT AND PROCESS FOR PRODUCING THE PHARMACEUTICAL PRODUCT |
| CN102552967B (en) * | 2006-12-15 | 2015-08-12 | 生命连结有限公司 | Gelatin-transglutaminase hemostatic dressings and encapsulant |
| CN103889447B (en) * | 2011-10-27 | 2015-11-25 | 巴克斯特国际公司 | hemostatic composition |
| CN102617884B (en) * | 2012-03-19 | 2014-03-05 | 嘉兴强特生物科技有限公司 | Production method of medical biological material for human serum albumin |
| CN107007881B (en) * | 2017-05-12 | 2020-11-27 | 深圳华诺生物科技有限公司 | Injectable self-healing gel for loading and releasing medicine and preparation method and application thereof |
| CN109589446A (en) * | 2017-09-30 | 2019-04-09 | 青海喜玛拉雅健康产业发展有限公司 | A kind of absorbable biological hemostatic material and preparation method thereof |
| IL261190A (en) * | 2018-08-16 | 2019-01-31 | Omrix Biopharmaceuticals Ltd | Stable liquid thrombin compositions |
| CN109453420B (en) * | 2018-11-29 | 2021-01-08 | 成都美益达医疗科技有限公司 | Hemostatic composition, preparation method and application thereof |
| KR20210143764A (en) * | 2019-03-20 | 2021-11-29 | 아스텔라스세이야쿠 가부시키가이샤 | Thrombin loaded hemostatic sheet |
| CN111053947A (en) * | 2019-12-03 | 2020-04-24 | 青岛职务帮网络服务有限公司 | Konjac glucomannan/fish gelatin hydrogel as well as preparation method and application thereof |
| CN112870453B (en) * | 2020-07-07 | 2022-01-07 | 深圳市第二人民医院(深圳市转化医学研究院) | Gelatin-type III collagen hydrogel and preparation method and application thereof |
-
2021
- 2021-12-10 CN CN202111509961.1A patent/CN114377189B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009128474A1 (en) * | 2008-04-16 | 2009-10-22 | 財団法人化学及血清療法研究所 | Method of producing thrombin-immobilized bioabsorbable sheet preparation |
| KR20190062170A (en) * | 2017-11-28 | 2019-06-05 | (주)다림티센 | Hemostatic agent and container containing the same |
| CN112368028A (en) * | 2018-05-09 | 2021-02-12 | 弗罗桑医疗设备公司 | Method for preparing a hemostatic composition |
Non-Patent Citations (3)
| Title |
|---|
| Cuiping Guo等.Synthesis of bovine serum albumin-gelatin composite adhesive hydrogels by physical crosslinking.Journal of Polymer Research.2022,第29卷全文. * |
| Ma X等.A biocompatible and biodegradable protein hydrogel with green and red autofluorescence: preparation, characterization and in vivo biodegradation tracking and modeling.Scientific reports.2016,第6卷(第6期),全文. * |
| Pathak J等.Thermo-reversibility, ergodicity and surface charge–temperature dependent phase diagram of anionic, cationic and neutral co-gels of gelatin–BSA complexes.RSC advances.2016,第6卷(第6期),全文. * |
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